allopurinol and Kidney-Diseases

In light of the recent pandemic, favipiravir (Avigan

Topics: Aldehyde Oxidase; Amides; Antiviral Agents; Biotransformation; Coronavirus Infections; COVID-19; Drug Interactions; Humans; Hyperuricemia; Kidney; Kidney Diseases; Molecular Structure; Organic Anion Transport Protein 1; Organic Anion Transporters; Organic Anion Transporters, Sodium-Independent; Organic Cation Transport Proteins; Pandemics; Pneumonia, Viral; Pyrazines; Uric Acid; Xanthine Oxidase

: Uric acid levels are higher in humans than in other mammals. Best known as an extracellular antioxidant, uric acid also increases salt sensitivity, fat storage, and lipogenesis. Xanthine oxidase-related oxidative stress may also induce endothelial dysfunction and renal vasoconstriction. Renal structure abnormalities contribute to salt-sensitive and uric acid-independent hypertension. Maternal hyperuricemia during pregnancy and hyperuricemia early in life are likewise independent risk factors for hypertension. Genetic polymorphism is potentially involved in the activity of xanthine oxidoreductase, but further studies are needed. Xanthine oxidase inhibition consistently decreases blood pressure in younger hypertensive patients, albeit modestly. Hyperuricemia affects one out of five adults as a result of the Western diet, insulin resistance, and renal dysfunction. This review advocates lifestyle changes to maintain uric acid levels within the normal range in young (pre)hypertensive individuals or normotensives with a family history of hypertension, metabolic disorders, or obesity; moreover, antihypertensive medications that increase uric acid levels should be avoided.

Topics: Animals; Antioxidants; Blood Pressure; Enzyme Inhibitors; Humans; Hypertension; Hyperuricemia; Kidney; Kidney Diseases; Oxidative Stress; Risk Factors; Uric Acid; Urogenital Abnormalities; Xanthine Oxidase

Gout is currently one of the most common causes of inflammatory arthritis in most industrialised countries. Apart from its high frequency, gout is associated with disability, poor quality of life and increased mortality and therefore represents an ever increasing public health concern. Substantial experimental and epidemiological evidence exists supporting the link between elevated levels of serum uric acid and several comorbidities including cardiovascular and kidney diseases. The cornerstone of effective gout management is long-term serum urate lowering below saturation concentrations (<6 mg/dL or <360 μmol/L) in order to promote crystal dissolution and prevent monosodium urate crystals formation. The management of gout includes not only pharmacological approaches, but also a number of nonpharmacologic interventions aiming at lessening attack risk, lowering uric acid levels and promoting general health while preventing the development of comorbidities. It is of great address whether urate lowering strategies can also lower cardiovascular risk and some preliminary studies in both animal and human subjects suggest that they might. Patient education and appropriate lifestyle advice are core aspects of management of hyperuricemia and gout. The two xanthine oxidase inhibitors currently available are effective as long-term urate lowering therapy although the greater efficacy and good tolerability of febuxostat as urate lowering agent has to be adequately considered especially when the reduction of serum uric acid levels to achieve the target is particularly ambitious and/or the presence of comorbidities increases the risk of adverse effects. Associated comorbidities and cardiovascular risk factors should be also addressed as an important part of the management of chronic hyperuricemia and gout.

Topics: Allopurinol; Cardiovascular Diseases; Chronic Disease; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Diseases; Life Style; Patient Education as Topic; Thiazoles; Xanthine Oxidase

The relationship between hypertension and chronic kidney disease (CKD) has long been the subject of controversy. The pathogenetic mechanisms of nephropathy in non-diabetic individuals with hypertension, as well as optimal hypertension treatment targets in populations with nephropathy remain important clinical concerns. This manuscript reviews breakthroughs in molecular genetics that have clarified the complex relationship between hypertension and kidney disease, answering the question of which factor comes first. An overview of the potential roles that hyperuricemia plays in the pathogenesis of hypertension and CKD and current blood pressure treatment guidelines in populations with CKD are discussed. The ongoing National Institutes of Health-sponsored Systolic Blood Pressure Intervention Trial (SPRINT) is underway to help answer these important questions. Enrollment of 9250 hypertensive SPRINT participants will be completed in 2013; important results on ideal blood pressure control targets for reducing nephropathy progression, cardiovascular disease end-points, and preserving cognitive function are expected. As such, many of the controversial aspects of hypertension management will likely be clarified in the near future.

Topics: Allopurinol; Animals; Antihypertensive Agents; Apolipoprotein L1; Apolipoproteins; Black People; Causality; Chronic Disease; Diabetic Angiopathies; Diabetic Nephropathies; Disease Management; Disease Models, Animal; Genetic Predisposition to Disease; Glomerulosclerosis, Focal Segmental; Goals; Humans; Hypertension; Hypertension, Renal; Hyperuricemia; Kidney Diseases; Lipoproteins, HDL; Multicenter Studies as Topic; Polymorphism, Genetic; Randomized Controlled Trials as Topic; Rats

Complete adenine phosphoribosyltransferase (APRT) deficiency is a rare inherited metabolic disorder that leads to the formation and hyperexcretion of 2,8-dihydroxyadenine (DHA) into urine. The low solubility of DHA results in precipitation of this compound and the formation of urinary crystals and stones. The disease can present as recurrent urolithiasis or nephropathy secondary to crystal precipitation into renal parenchyma (DHA nephropathy). The diagnostic tools available-including stone analysis, crystalluria, and APRT activity measurement-make the diagnosis easy to confirm when APRT deficiency is suspected. However, the disease can present at any age, and the variability of symptoms can present a diagnostic challenge to many physicians. The early recognition and treatment of APRT deficiency are of crucial importance for preventing irreversible loss of renal function, which still occurs in a non-negligible proportion of cases. This review summarizes the genetic and metabolic mechanisms underlying stone formation and renal disease, along with the diagnosis and management of APRT deficiency.

Topics: Adenine; Adenine Phosphoribosyltransferase; Allopurinol; Animals; Biomarkers; Disease Progression; Enzyme Inhibitors; Genetic Predisposition to Disease; Humans; Kidney Diseases; Metabolism, Inborn Errors; Phenotype; Predictive Value of Tests; Prognosis; Recurrence; Urolithiasis; Xanthine Dehydrogenase

After uric acid was recognized as the causative factor in gout, increased prevalence of renal disease and hypertension in this patient population caught the attention of the medical community. Thus, it has been proposed that uric acid might have caused these disorders. However, uric acid suffered a long period of ignorance in which it was considered a metabolically inert substance. However, recent years has witnessed a resurrection of interest. Experimental studies showed an association between increased uric acid and renal arteriolar disease and hypertension. These preliminary results were supported with clinical studies. However, controversy regarding the precise pathophysiologic role of uric acid in inducing hypertension and renal disease remains to be elucidated. Despite being limited at this time, a few randomized intervention studies showed that even treatment of asymptomatic hyperuricemia was beneficial in terms of blood pressure regulation and kidney function. In this review, we focus on the pathophysiologic role of uric acid in the development and progression of renal disease and hypertension. We also discuss recent clinical evidence suggesting a causal role of uric acid in these disease states.

Topics: Allopurinol; Animals; Blood Pressure; Clinical Trials as Topic; Diet; Disease Progression; Fructose; Humans; Hypertension; Hyperuricemia; Kidney Diseases; Mice; Rats; Risk Factors; Uric Acid

It is suggested that hyperuricemia has a pathogenetical role in the onset and progression of hypertension and renal disease in both clinical studies and animal experiments. The treatment of hyperuricemia by allopurinol was reported to cause improvement of hypertension and renal function, and the withdrawal of allopurinol treatment was also reported to bring worsening of hypertension and acceleration of the rate of loss of renal function in the patients with chronic kidney disease (CKD). However, the necessity of treatment against hyperuricemia in CKD has to be warranted by large scale clinical experiments in the future.

Topics: Allopurinol; Animals; Chronic Disease; Disease Progression; Humans; Hypertension; Hyperuricemia; Kidney Diseases; Metabolic Syndrome; Risk Factors

To review the current concepts in toxic and drug-induced granulomatous reactions.. Granulomatous reactions are induced by various chemical agents, treatments or foreign bodies. According to the breaking way into the organism, the lungs, the liver, the kidneys or the skin are mainly concerned, but systemic granulomatosis mimicking sarcoidosis is possible. Therefore systematic analysis of environmental, occupational and leisure exposures and quest for medical or illicit drugs is mandatory to identify the responsible agent. Over the recent period, chronic beryllium disease, interferon-alpha therapy, BCG immunotherapy and allopurinol have been more frequently involved.. Literature review uncovers a variety of potential toxic exposures and highlights the necessity of a clear sighted research to identify them.

Topics: Allopurinol; Antimetabolites; BCG Vaccine; Berylliosis; Chemical and Drug Induced Liver Injury; Granuloma; Humans; Immunologic Factors; Interferon-alpha; Kidney Diseases; Lung Diseases; Sarcoidosis; Skin Diseases

Topics: Animals; Bacteria; Bacterial Physiological Phenomena; Bacterial Translocation; Chronic Disease; Cytokines; Diuretics; Fermentation; Humans; Inflammation; Intestinal Absorption; Intestines; Iron; Iron Chelating Agents; Kidney Diseases; Probiotics; Rats; Reactive Oxygen Species; Uremia; Xanthine Oxidase

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Pacing, Artificial; Cardiography, Impedance; Cardiomyopathy, Dilated; Chronic Disease; Clinical Trials as Topic; Comorbidity; Disease Management; Enoximone; Heart Failure; Hemodynamics; Humans; Kidney Diseases; Natriuretic Peptide, Brain; Natriuretic Peptides; Nitric Oxide; Nitric Oxide Synthase; Pacemaker, Artificial; Phosphodiesterase Inhibitors; Practice Guidelines as Topic; Xanthine Oxidase

Topics: Acute Disease; Benzothiadiazines; Diuretics; Female; Gout; Humans; Hypertension; Hyperuricemia; Kidney Diseases; Metabolic Syndrome; Obesity; Postmenopause; Sodium Chloride Symporter Inhibitors; Urate Oxidase; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Allopurinol; Arteriosclerosis; Benzbromarone; Enzyme Inhibitors; Gout; Humans; Hyperuricemia; Kidney Diseases; Probenecid; Prognosis; Risk; Uricosuric Agents; Urinary Calculi; Xanthine Oxidase

Topics: Allopurinol; Chromosomes, Human, Pair 16; Genes, Dominant; Gout; Humans; Hyperuricemia; Kidney Diseases

Topics: Allopurinol; Creatinine; Humans; Inappropriate ADH Syndrome; Kidney Diseases; Kidney Tubules; Losartan; Metabolic Clearance Rate; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid; Xanthine Oxidase

Topics: Humans; Kidney Diseases; Xanthine; Xanthine Dehydrogenase; Xanthine Oxidase

The serum levels of uric acid, hypoxanthine and xanthine tended to increase with the decrease of renal function. This mechanism was thought to be the decreased excretion of these materials from the kidney. More than ninety percent of the patients with renal insufficiency (Ccr < or = 30 ml/min) showed hyperuricemia. In general, the gouty arthritis was reported to be uncommon in the patients with secondary hyperuricemia due to renal insufficiency. However, the frequency of gouty arthritis was reported to be high in the patients with polycystic disease and lead nephropathy. The therapeutic standard for secondary hyperuricemia with renal insufficiency was not established. Allopurinol is the drug of choice for controlling hyperuricemia due to renal insufficiency in many cases. In renal insufficiency, the drug must be used cautiously and in reduced dosage because increased serum concentration of oxipurinol, active metabolite of allopurinol, may induce severe side effect.

Topics: Allopurinol; Arthritis, Gouty; Humans; Kidney Diseases; Purine Nucleotides; Uric Acid

A large number of pharmacological agents affect the serum concentration of uric acid. Some drugs raise serum uric acid level by an increase in uric acid production or a decrease in uric acid excretion, while others lower serum uric acid level by a decrease in uric acid production or an increase in uric acid excretion. In addition, some drugs show so-called biphasic effect; ie, hyperuricemic in lower doses but hypouricemic in higher doses. Hyperuricemic agents contribute to gout and/or urate nephropathy. Among them, pyrazinamide is often used to determine the defective site(s) of uric acid transport in renal tubules in conjunction with uricosuric agents, such as benzbromarone or probenecid. In contrast, the clinical significance of hypouricemic agents other than uricosuric agents has not been emphasized. However, some may induce acute uric acid nephropathy by a significant increase in uric acid excretion. In this review, drugs affecting uric acid metabolism are summarized with regard to their mechanism of action and clinical significance.

Topics: Allopurinol; Diuretics; Fructose; Gout; Gout Suppressants; Humans; Inosine; Kidney Diseases; Niacin; Purines; Uric Acid; Xylitol

APRT deficiency is an enzyme disorder which is inherited as an autosomal recessive trait. The use of adenine in purine metabolism is disturbed and it accumulates in the body, where it is oxidised by xanthine oxidase to poorly insoluble 2, 8-dihydroxyadenine (DHA). The dihydroxyadenine forms stones which cause recurrent urolithiasis, frequent episodes of urinary tract infection or interstitial nephritis, and finally renal insufficiency in some cases. We report a case of APRT deficiency discovered by urine examination. The patient was a 33-year-old man who had never had any episodes of urolithiasis. He was admitted to our hospital because of pseudoarthrosis of his left arm caused by a traffic accident. His urinalysis revealed no proteinuria nor hematuria, but disclosed numerous round brown crystals in the sediment. These crystals had the characteristics of 2, 8-DHA. The enzyme activity of APRT in his blood was completely deficient. He was diagnosed as an APRT* QO homozygote. In addition, diagnostic imaging revealed that his right kidney was poorly hypoplastic and the pelvis of his left kidney was extra-renal. The renal function was slightly disturbed. In Japan 6 cases of 2, 8-DHA urolithiasis associated with hypoplastic kidney had been reported by 1989. Theoretically, the incidence of hypoplastic kidney is around 20% of all 2, 8-DHA urolithiasis cases. We suspect a genetic correlation between hypoplastic kidney and APRT deficiency. This patient was treated with Allopurinol, which inhibits the process of xanthine oxidation, after which crystals were no longer detected in his urine.

Topics: Adenine; Adenine Phosphoribosyltransferase; Adult; Allopurinol; Crystallization; Homozygote; Humans; Kidney Diseases; Male; Urinary Calculi

To review the pathophysiology, pathology, and clinical findings of allopurinol hypersensitivity syndrome (AHS), an infrequent but life-threatening adverse effect of allopurinol therapy.. A MEDLINE search (key terms hepatitis, interstitial nephritis, severe hypersensitivity, severe toxicity, vasculitis, toxic epidermal necrolysis, Lyell's syndrome, erythema multiforme, and Stevens-Johnson syndrome) was used to identify cases reported in the literature through the end of 1990.. All cases evaluated met Singer and Wallace's diagnostic criteria for AHS.. We extracted data from 101 cases of AHS reported in the literature. The following information, when available, was analyzed: (1) patient data (age, gender, medical history), (2) treatment data (daily dosage of allopurinol, duration of treatment, indications, concomitant medications, and (3) adverse-event data.. Patients were mostly middle-aged men with hypertension and/or renal failure receiving excessive doses of allopurinol primarily for asymptomatic hyperuricemia. Cutaneous rash and fever were the most common clinical findings.. Although the pathophysiologic pathway leading to the development of AHS is unknown, it probably involves an immunologic mechanism following allopurinol accumulation in patients with poor renal function. Our findings suggest that the accepted diagnostic criteria for AHS may be too broad, and we recommend the application of more restrictive criteria. There is no effective treatment for AHS. The use of allopurinol only for accepted indications and in dosages adjusted for a patient's renal function may be the only means of minimizing the incidence of AHS.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Allopurinol; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Female; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; Risk Factors; Skin Diseases

Topics: Allopurinol; Female; Gout; Humans; Kidney Diseases; Kidney Transplantation; Male

Uric acid, as the end-product of purine metabolism in humans, presents a clinical problem because of its relative insolubility, particularly in the acid environment of the distal nephron of the kidney. As a result, states of enhanced purine catabolism increase the urate load on the kidney, leading to intrarenal precipitation. Major causes of increased purine metabolism are malignancies with rapid cell turnover, such as leukemias and lymphomas, and the added acceleration of cell lysis that occurs with chemotherapy and radiation. Serum urate levels rise rapidly, and acute renal failure occurs as a consequence of tubular deposition of urate and uric acid. The keys to the diagnosis of acute uric acid nephropathy are the appropriate clinical setting of increased cell lysis, oliguria, marked hyperuricemia, and hyperuricosuria. A urinary uric acid-to-creatinine ratio greater than 1 helps to distinguish acute uric acid nephropathy from other catabolic forms of acute renal failure in which serum urate is elevated. Preventive treatment involves pharmacologic xanthine oxidase inhibition with allopurinol and alkaline diuresis. Occasionally, acute renal failure occurs despite allopurinol because of the tubular precipitation of the precursor metabolites, such as xanthine, which accumulate with xanthine oxidase inhibition. Dialysis therapy may be required both to correct azotemia and to reduce the body burden of urate. Hemodialysis is preferred because it can achieve greater clearance than other dialysis modes.

Topics: Acute Disease; Allopurinol; Chemical Phenomena; Chemistry, Physical; Humans; Kidney; Kidney Diseases; Renal Dialysis; Uric Acid

Gout is a clinical syndrome encompassing a group of metabolic diseases that are all characterized by abnormal uric acid metabolism. In its fullest form, gout is defined by: an increase in the serum urate concentration; characteristic, recurrent, acute arthritic attacks, with monosodium urate monohydrate crystals demonstrable in synovial fluid leukocytes; tophi, usually in and around joints of the extremities, composed of monosodium urate monohydrate deposits; renal disease, often accompanied by hypertension with glomerular, tubular, interstitial, and vascular involvement; and uric acid nephrolithiasis. Any combination of these manifestations may occur, although tophi and urate nephropathy rarely antedate gouty arthritis.

Topics: Acute Disease; Adult; Allopurinol; Anti-Inflammatory Agents; Arthritis; Arthrography; Calcinosis; Chronic Disease; Colchicine; Female; Gout; Humans; Kidney Calculi; Kidney Diseases; Middle Aged; Probenecid; Uric Acid

Topics: Allopurinol; Aminoglycosides; Analgesics; Anti-Bacterial Agents; Anti-Inflammatory Agents; Captopril; Cephalosporins; Cisplatin; Diuretics; Glomerulonephritis; Gold; Humans; Kidney; Kidney Diseases; Kidney Tubular Necrosis, Acute; Lithium; Nephritis, Interstitial; Penicillamine; Penicillins; Rifampin; Semustine; Sulfonamides; Tetracycline; Trimethadione

Topics: Allopurinol; Arthritis; Aspirin; Blood Urea Nitrogen; Glomerular Filtration Rate; Gout; Humans; Kidney Diseases; Uric Acid

Topics: Allopurinol; Gout; Humans; Kidney Calculi; Kidney Diseases; Nephritis, Interstitial; Purines; Uric Acid

Topics: Acute Disease; Allopurinol; Arthritis; Aspirin; Colchicine; Coronary Disease; Diuretics; Gout; Humans; Hypoxanthine Phosphoribosyltransferase; Indomethacin; Kidney; Kidney Calculi; Kidney Diseases; Lead Poisoning; Lymphoproliferative Disorders; Myeloproliferative Disorders; Phenylbutazone; Platelet Aggregation; Probenecid; Purine-Pyrimidine Metabolism, Inborn Errors; Pyrazinamide; Ribose-Phosphate Pyrophosphokinase; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Biological Transport; Diuretics; Glomerular Filtration Rate; Gout; Humans; Hypoxanthine Phosphoribosyltransferase; Kidney Diseases; Kidney Tubules; Lactates; Lesch-Nyhan Syndrome; Nucleosides; Nucleotides; Purines; Risk; Sodium; Uric Acid

The spectrum of kidney and urinary tract disorders related to purines comprises acute hyperuricosuric nephropathy, chronic urate nephropathy and urolithiasis. Two factors in the development of acute hyperuricosuric nephropathy are increased uric acid concentration and low pH in the tubular fluid. Chronic urate nephropathy still possess several problems: incidence (although this seems to be decreasing, presumably owing to effective prevention), the source of interstitial urate, the cause of the interstitial deposition of urate, and the role of urate deposits in the pathogenesis of the interstitial nephropathy. The relation of the experimental nephropathy to the pathogenesis of chronic urate nephropathy in the human is not yet clear but a model is proposed according to which interstitial urate derives from two sources: hyperuricaemic plasma and hyperuricosuric tubular fluid. Urolithiasis related to purines leads to uric acid-urate stones, xanthine stones, 2,8-dihydroxyadenine stones, iatrogenic xanthine and oxipurinol stones, and possibly calcium stones. Pathogenetic factors in uric acid lithiasis are hyperuricosuria (whether due to an inborn enzyme abnormality or of unknown aetiology) and low urinary pH; oliguria is a contributory factor. There remain several open questions about uric acid lithiasis: incidence, the shift of its location from lower to upper urinary tract, the interplay of pathogenetic factors, and the role of compounds which inhibit crystallization.

Topics: Adenine Phosphoribosyltransferase; Allopurinol; Animals; Calcium; Gout; Humans; Hydrogen-Ion Concentration; Hypoxanthine Phosphoribosyltransferase; Kidney Calculi; Kidney Diseases; Kidney Failure, Chronic; Oxypurinol; Purines; Sodium; Solubility; Uric Acid; Urologic Diseases; Xanthine Oxidase; Xanthines

Benzbromarone1 is a benzofuran derivative which lowers serum urate and increases urinary urate excretion in normal, hyperuricaemic and gouty subjects. In open short- and long-term studies benzbromarone reduced serum uric acid levels by one-third to one-half and maintained its effectiveness for periods of up to 8 years. Single-dose experimental studies have shown benzbromarone to have a urate-lowering effect similar to that of a therapeutic dose of probenecid or sulphinpyrazone, but unlike these drugs benzbromarone can be administered in a once daily regimen. In 2 short-term comparative therapeutic trials in a small number of patients with hyperuricaemia, 80mg of micronised benzbromarone daily was at least as effective as 1000mg of probenecid or 300mg of allopurinol daily in lowering serum uric acid levels. Side-effects during benzbromarone administration are usually mild and primarily gastrointestinal in nature.

Topics: Aspirin; Benzbromarone; Benzofurans; Drug Interactions; Fasting; Gout; Humans; Kidney Diseases; Kinetics; Lipid Metabolism; Pyrazinamide; Triglycerides; Uric Acid; Xanthine Oxidase

Topics: Acetazolamide; Allopurinol; Humans; Kidney Diseases; Leukemia; Lymphoma; Renal Dialysis; Uric Acid

Topics: Abnormalities, Drug-Induced; Alkylating Agents; Allopurinol; Alopecia; Antimetabolites; Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Cyclophosphamide; Drug Synergism; Female; Fetus; Humans; Kidney Calculi; Kidney Diseases; Kidney Tubules; Mechlorethamine; Mercaptopurine; Neoplasms; Pregnancy; Pregnancy Complications; Uric Acid; Vincristine

Topics: Adult; Allopurinol; Child; Drug Hypersensitivity; Drug Interactions; Gout; Humans; Iron; Kidney Diseases; Nucleic Acids; Purines; Pyrimidines; Tryptophan; Uric Acid; Urinary Calculi; Xanthines

Hyperuricemia has been associated with the development of hypertension, cardiovascular, and renal disease. However, there is no data about the effect of lowering uric acid level on renal functions and proteinuria in renal transplant recipients. This study aimed to investigate the effect of allopurinol treatment on renal functions in renal transplant recipients (RTR).. A total of 245 patients with renal transplantation were included in this randomized, placebo-controlled study. Patients were randomized to receive either placebo (121 patients) or 300 mg/day allopurinol (124 patients). We have examined uric acid, urinary protein creatinin ratio, MDRD (the modification of diet in renal diseases) and CRP (C-reactive protein) before and 24 weeks after treatment in both group.. In the allopurinol group, the mean serum uric acid levels, eGFR (estimated glomerular filtration rate), and creatinine urinary albumin creatinin ratio (UACR) significantly improved (p < 0.001). Also uric acid level was positively correlated with the UACR (r = 0,645 p < 0.001) and negatively correlated with MDRD (r = -0,387 p < 0.05) in allopurinol treatment group. A statistically significant increase in CRP level was observed (p < 0,05) in plasebo group. Multivariate regression analysis showed that uric acid was positively correlated with UACR (r = 0,473, β = 0.021, p = 0.002) and negatively correlated with MDRD (r = -0554 β = 0.016, P = 0.001) in allopurinol treatment RTR.. Urate, a salt of uric acid, is lowered by allopurinol treatment resulting in improved eGFR and decreased proteinuria, when compared to the placebo group. Therefore, we suggest that allopurinol therapy should be part of the management of kidney transplant patients with normal kidney function. Long-term follow-up studies will be useful in revealing the effect of uric acid management on kidney functions and proteinuria.

Topics: Allopurinol; C-Reactive Protein; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Kidney Transplantation; Proteinuria; Treatment Outcome; Uric Acid

Contrast-induced nephropathy (CIN) is a major drawback in percutaneous coronary intervention (PCI). Significant uricosuria has been reported following contrast exposure. Allopurinol-a xanthine oxidase inhibitor-has been suggested to prevent the formation of oxygen-free radicals, which may contribute to CIN. The aim of the present study was to evaluate the possible efficacy of allopurinol in preventing CIN.. In this double-blind placebo-controlled trial, patients with an estimated glomerular filtration rate ≥60 mL/min who were admitted for elective PCI, were randomized to receive either allopurinol 600 mg or a placebo administered 24 h before the procedure, and again immediately before the procedure. Blood samples were drawn at 24 h before and 24 h after contrast exposure to measure serum creatinine (SCr), uric acid, and serum cystatin-c.. The baseline characteristics were almost similar between the placebo and allopurinol groups. The overall change in SCr and the rate of CIN, which is defined as ≥25% increase in serum cystatin-c relative to baseline, failed to show a significant difference between the two groups. When adjusted on the baseline cystatin-c, SCr, sex, and positive family history, the difference in the overall increase in serum cystatin-c was statistically significantly lower in the allopurinol group.. Allopurinol administration in patients undergoing PCI failed to show efficacy in preventing CIN. Nevertheless, this effect should be further evaluated in the patient population with chronic kidney disease.

Topics: Aged; Allopurinol; Contrast Media; Creatinine; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Percutaneous Coronary Intervention

To determine the efficacy and safety of increasing the allopurinol dose above the proposed creatinine clearance-based dose in patients with gout.. Patients with gout who had been receiving a stable dose of allopurinol for ≥ 1 month were recruited. The dose of allopurinol was increased to obtain the target serum urate level of <0.36 mmoles/liter (<6 mg/dl). Patients were seen monthly until the serum urate concentration was <0.36 mmoles/liter for 3 consecutive months and then were seen every 3 months for at least 12 months. Data were analyzed using the dosage of allopurinol (mg/day) greater than the recommended dosage, as defined by the Hande criteria.. Ninety patients were enrolled. The mean age of the patients was 58.7 years (range 27-83 years), 87.9% were male, and 81.9% were of European ancestry. Forty-five patients had a serum urate concentration of ≥ 0.36 mmoles/liter, and the dose of allopurinol was increased in these patients. Rashes developed in 3 patients, and either allopurinol was discontinued or dose escalation was ceased in these patients. Seven patients were lost to followup or developed intervening medical problems that precluded dose escalation. In 31 (88.8%) of 35 patients who completed the study, the serum urate level was <0.36 mmoles/liter at 12 months. Two of the 5 patients who had a serum urate level ≥ 0.36 mmoles/liter had undetectable levels of plasma oxypurinol, indicating noncompliance with allopurinol treatment. A significant reduction in the serum urate concentration was observed for all allopurinol doses above the recommended dose. Eighteen of 45 patients were receiving furosemide; those receiving furosemide were just as likely as those not receiving furosemide to achieve a serum urate concentration of <0.36 mmoles/liter (72% versus 88.5%; P = 0.24). Patients receiving furosemide required a higher dose of allopurinol to achieve the target serum urate concentration. No serious adverse events were observed.. Increasing the dose of allopurinol above the proposed creatinine clearance-based dose led to a significant reduction in the serum urate concentration. Approximately 89% of patients achieved a serum urate concentration of <0.36 mmoles/liter. In this cohort, toxicity was not increased in patients receiving higher doses of allopurinol, including those with renal impairment.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Creatinine; Dose-Response Relationship, Drug; Drug Monitoring; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Diseases; Male; Middle Aged; Treatment Outcome; Uric Acid

The purpose of this study was to compare urate-lowering (UL) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate (sUA) > or = 8.0 mg/dL in a six-month trial.. Subjects (n = 2,269) were randomized to febuxostat 40 mg or 80 mg, or allopurinol 300 mg (200 mg in moderate renal impairment). Endpoints included the proportion of all subjects with sUA <6.0 mg/dL and the proportion of subjects with mild/moderate renal impairment and sUA <6.0 mg/dL. Safety assessments included blinded adjudication of each cardiovascular (CV) adverse event (AE) and death.. Comorbidities included: renal impairment (65%); obesity (64%); hyperlipidemia (42%); and hypertension (53%). In febuxostat 40 mg, febuxostat 80 mg, and allopurinol groups, primary endpoint was achieved in 45%, 67%, and 42%, respectively. Febuxostat 40 mg UL was statistically non-inferior to allopurinol, but febuxostat 80 mg was superior to both (P < 0.001). Achievement of target sUA in subjects with renal impairment was also superior with febuxostat 80 mg (72%; P < 0.001) compared with febuxostat 40 mg (50%) or allopurinol (42%), but febuxostat 40 mg showed greater efficacy than allopurinol (P = 0.021). Rates of AEs did not differ across treatment groups. Adjudicated (APTC) CV event rates were 0.0% for febuxostat 40 mg and 0.4% for both febuxostat 80 mg and allopurinol. One death occurred in each febuxostat group and three in the allopurinol group.. Urate-lowering efficacy of febuxostat 80 mg exceeded that of febuxostat 40 mg and allopurinol (300/200 mg), which were comparable. In subjects with mild/moderate renal impairment, both febuxostat doses were more efficacious than allopurinol and equally safe. At the doses tested, safety of febuxostat and allopurinol was comparable.. NCT00430248.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Comorbidity; Dose-Response Relationship, Drug; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperlipidemias; Hypertension; Hyperuricemia; Kidney Diseases; Male; Middle Aged; Obesity; Thiazoles; Treatment Outcome; United States; Uric Acid; Young Adult

Hyperuricemia is associated with hypertension, inflammation, renal disease progression, and cardiovascular disease. However, no data are available regarding the effect of allopurinol in patients with chronic kidney disease.. We conducted a prospective, randomized trial of 113 patients with estimated GFR (eGFR) <60 ml/min. Patients were randomly assigned to treatment with allopurinol 100 mg/d (n = 57) or to continue the usual therapy (n = 56). Clinical, biochemical, and inflammatory parameters were measured at baseline and at 6, 12, and 24 months of treatment. The objectives of study were: (1) renal disease progression; (2) cardiovascular events; and (3) hospitalizations of any causes.. Serum uric acid and C-reactive protein levels were significantly decreased in subjects treated with allopurinol. In the control group, eGFR decreased 3.3 +/- 1.2 ml/min per 1.73 m(2), and in the allopurinol group, eGFR increased 1.3 +/- 1.3 ml/min per 1.73 m(2) after 24 months. Allopurinol treatment slowed down renal disease progression independently of age, gender, diabetes, C-reactive protein, albuminuria, and renin-angiotensin system blockers use. After a mean follow-up time of 23.4 +/- 7.8 months, 22 patients suffered a cardiovascular event. Diabetes mellitus, previous coronary heart disease, and C-reactive protein levels increased cardiovascular risk. Allopurinol treatment reduces risk of cardiovascular events in 71% compared with standard therapy.. Allopurinol decreases C-reactive protein and slows down the progression of renal disease in patients with chronic kidney disease. In addition, allopurinol reduces cardiovascular and hospitalization risk in these subjects.

Topics: Aged; Allopurinol; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Chi-Square Distribution; Chronic Disease; Disease Progression; Glomerular Filtration Rate; Gout Suppressants; Hospitalization; Humans; Hyperuricemia; Inflammation Mediators; Kaplan-Meier Estimate; Kidney Diseases; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Spain; Time Factors; Treatment Outcome; Uric Acid

Hyperuricemia is associated strongly with the development of hypertension, renal disease, and progression. Allopurinol decreases serum uric acid levels by inhibiting the enzyme xanthine oxidase. We hypothesized that administrating allopurinol to decrease serum uric acid levels to the normal range in hyperuricemic patients with chronic kidney disease may be of benefit in decreasing blood pressure and slowing the rate of renal disease progression in these patients.. We conducted a prospective, randomized, controlled trial of 54 hyperuricemic patients with chronic kidney disease. Patients were randomly assigned to treatment with allopurinol, 100 to 300 mg/d, or to continue the usual therapy for 12 months. Clinical, hematologic, and biochemical parameters were measured at baseline and 3, 6, and 12 months of treatment. We define our study end points as: (1) stable kidney function with less than 40% increase in serum creatinine level, (2) impaired renal function with creatinine level increase greater than 40% of baseline value, (3) initiation of dialysis therapy, and (4) death.. One patient in the treatment group dropped out because of skin allergy to allopurinol. Serum uric acid levels were significantly decreased in subjects treated with allopurinol, from 9.75 +/- 1.18 mg/dL (0.58 +/- 0.07 mmol/L) to 5.88 +/- 1.01 mg/dL (0.35 +/- 0.06 mmol/L; P < 0.001). There were no significant differences in systolic or diastolic blood pressure at the end of the study comparing the 2 groups. There was a trend toward a lower serum creatinine level in the treatment group compared with controls after 12 months of therapy, although it did not reach statistical significance (P = 0.08). Overall, 4 of 25 patients (16%) in the allopurinol group reached the combined end points of significant deterioration in renal function and dialysis dependence compared with 12 of 26 patients (46.1%) in the control group (P = 0.015).. Allopurinol therapy significantly decreases serum uric acid levels in hyperuricemic patients with mild to moderate chronic kidney disease. Its use is safe and helps preserve kidney function during 12 months of therapy compared with controls. Results of this study need to be confirmed with an additional prospective trial involving a larger cohort of patients to determine the long-term efficacy of allopurinol therapy and in specific chronic kidney disease subpopulations.

Topics: Adult; Aged; Allopurinol; Creatinine; Disease Progression; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Hypertension; Hyperuricemia; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Proteinuria; Renal Dialysis; Treatment Outcome; Uric Acid; Xanthine Oxidase

A single oral dose of 20 mg febuxostat was administered to subjects with normal, mild or moderate impairment in renal function. There was less than a 2-fold difference in AUC of plasma unchanged febuxostat among the renal function groups, and changes in plasma urate levels from pre-dose levels were not significant. A total of five adverse events were reported with all mild in severity. The results indicate that renal impairment will have little clinical impact on the pharmacokinetics (PK), pharmacodynamics (PD) and safety of the study drug.

Topics: Area Under Curve; Enzyme Inhibitors; Febuxostat; Female; Humans; Kidney; Kidney Diseases; Male; Renal Insufficiency; Thiazoles; Time Factors; Xanthine Oxidase

To investigate the ameliorative effect on chronic uric acid nephropathy (CUAN) by integrating western and traditional Chinese medicine (IWTCM).. The 136 CUAN patients were divided into two groups at random, the therapy group of 86 patients were treated by Chinese medicine and allopurinol, and the control group of 50 patients were treated only by allopurinol. The curative effect and the related index such as blood uric acid, renal function, urinary protein, microproteins, blood lipid and hyperviscosity were determined before and after being treated.. After three months treatment, the total effective rate in the therapy group (90.7%) was significantly higher (P < 0.01) than that of the control group (56%). The therapy group is also superior to the control group in improving renal function, lipid metabolism and hyperviscosity, decreasing blood uric acid, urinary protein, microproteins in evidence (P < 0.05, P < 0.01).. IWTCM can obviously improve the ameliorative effect on chronic uric acid nephropathy.

Topics: Adult; Aged; Allopurinol; Blood Viscosity; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Kidney Diseases; Male; Medicine, Chinese Traditional; Middle Aged; Phytotherapy; Uric Acid

Ionic, high-osmolality contrast medium causes nephrotoxicity associated with increased intrarenal adenosine production. To test the hypothesis that oxygen free radicals (produced during intrarenal adenosine catabolism to xanthine) should be implicated in the pathogenesis of ionic, high-osmolality contrast medium nephrotoxicity in humans and to determine whether magnesium protects the kidney from oxygen free radical injury following contrast, 39 patients with mild renal dysfunction were divided into low (LoMg++) and normal (NlMg++) magnesium states and randomized to precoronary angiography oral allopurinol (a xanthine oxidase inhibitor) or placebo. Creatinine clearance and urinary xanthine excretion were measured before and after angiography. Forty-eight hours after contrast medium exposure, placebo-treated LoMg++ and NlMg++ patients had 61%+/-5% and 67%+/-6% increases in urinary xanthine excretion, respectively; however, placebo-treated LoMg++ patients had a greater (79%+/-9% v 35%+/-6%; P < 0.01) decrease in creatinine clearance than placebo-treated NlMg++ patients. Allopurinol-treated LoMg++ and NlMg++ patients had no significant change in urinary xanthine excretion, but did have 40%+/-7% and 33%+/-5% decreases, respectively, in creatinine clearance 48 hours after contrast medium exposure. There was no difference in renal dysfunctional response among placebo-treated NlMg++ patients or allopurinol-treated LoMg++ or NlMg++ patients. These data suggest (1) that oxygen free radicals contribute to ionic, high-osmolality contrast medium nephrotoxicity in hypomagnesemic patients with mild renal disease and (2) that magnesium attenuates the nephrotoxicity mediated by oxygen free radicals.

Topics: Adenosine; Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Contrast Media; Coronary Angiography; Diatrizoate; Enzyme Inhibitors; Free Radicals; Humans; Kidney; Kidney Diseases; Magnesium; Middle Aged; Osmolar Concentration; Prospective Studies; Reactive Oxygen Species; Xanthine Oxidase

In a prospective randomized study, the effects of a calcium antagonist (nifedipine) and a xanthine oxidase inhibitor (allopurinal) on high energy shock wave induced impairment of renal function were examined. A total of 40 patients with renal pelvis or caliceal stones undergoing anesthesia-free extracorporeal shock wave lithotripsy (ESWL) without auxiliary measures was randomly assigned to 4 groups. Group 1 received no medication and the others received nifedipine (group 2), allopurinol (group 3) or nifedipine plus allopurinol (group 4), respectively. Nifedipine (20 mg. each) or allopurinol (0.2 gm. each) was given orally 3 times a day for a total of 4 days beginning the night before ESWL. To assess renal function the urinary excretions of beta 2-microglobulin, albumin and Tamm-Horsfall protein were determined by radioimmunoassay. After ESWL there was a significant increase in urinary beta 2-microglobulin and albumin (p < 0.001), and the urinary Tamm-Horsfall protein decreased significantly (p < 0.01) compared with before ESWL in group 1. In groups 2 and 4, however, all of the parameters after ESWL were not significantly different compared with the values before ESWL. Although the levels of urinary beta 2-microglobulin and albumin after ESWL were significantly higher (p < 0.05) than the pre-ESWL levels in group 3, the changes in urinary albumin and Tamm-Horsfall protein were milder in group 3 than in group 1. In addition, the urinary albumin level in group 2 and the urinary beta 2-microglobulin or albumin level in group 4 were less significantly different (p < 0.05) than the levels in group 1. All parameters before ESWL were not significantly different among the groups. Our results indicated that nifedipine and/or allopurinol exhibits a protective effect on high energy shock wave induced renal damage.

Topics: Adolescent; Adult; Allopurinol; Female; Humans; Kidney Calculi; Kidney Diseases; Kidney Function Tests; Kidney Pelvis; Lithotripsy; Male; Middle Aged; Nifedipine; Prospective Studies

Topics: Adolescent; Adult; Aged; Allopurinol; Creatinine; Female; Follow-Up Studies; Humans; Hypertension; Kidney Diseases; Male; Pedigree; Prospective Studies; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid

Topics: Allopurinol; Clinical Trials as Topic; Drug Evaluation; Gout; Humans; Kidney Diseases; Kidney Tubules; Male; Uric Acid

Topics: Acute Kidney Injury; Adult; Aged; Allopurinol; Benzofurans; Clinical Trials as Topic; Gout; Humans; Kidney Diseases; Kidney Failure, Chronic; Metabolic Clearance Rate; Middle Aged; Urea; Uric Acid

Topics: Animals; Fibrosis; Hyperuricemia; Inflammation; Iridoids; Kidney Diseases; Mice; Molecular Docking Simulation; Transforming Growth Factor beta; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Diseases; Male; Treatment Outcome

Allopurinol, widely used in the treatment of hyperuricemia and gout, has been shown to cause severe cutaneous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, as well as systemic reactions such as DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms). The HLA-B*5801 allele is known to be a risk factor for severe cutaneous manifestations of hypersensitivity to allopurinol, mostly in Asian populations.. We report the observation of a 47-year-old Chinese patient, with no previous medical history, carrying the HLA-B*5801 allele, who developed an isolated allopurinol hypersensitivity necrotizing renal vasculitis without cutaneous manifestations.. . The identification of this allele should be proposed before prescribing allopurinol in patients originating from certain regions of Asia, and the imputability of allopurinol should be evoked in case of necrotizing renal vasculitis, even without associated cutaneous involvement.

Topics: Allopurinol; China; Drug Hypersensitivity; Drug Hypersensitivity Syndrome; Gout Suppressants; HLA-B Antigens; Humans; Kidney Diseases; Middle Aged; Stevens-Johnson Syndrome; Vasculitis

To explore the effect of the granules made by new-medicinal parts of Crocus sativus(NMPCS) on hyperuricemia(HUA) in rats, the rat model of HUA was established by intramuscular injection of 3% potassium oxonate and intraperitoneal injection of 4% pyrazinamide. The content of serum uric acid was monitored every week for 3 consecutive weeks. After the experiment, the levels of serum uric acid, urine uric acid, serum creatinine, blood urea nitrogen(BUN), and xanthine oxidase(XOD) were determined. The protein and gene expressions of XOD were determined by Western blot method and fluorescence quantitative polymerase chain reaction(qPCR), and the morphological changes in the liver tissue were performed by hematoxylin-eosin(HE) staining. The results showed that as compared with the model group, the levels of serum uric acid in the positive drug group and the low, medium, and high-dose NMPCS groups were lower(P<0.05), the levels of urine uric acid in the high-dose NMPCS group were decreased(P<0.01), and there was no statistical difference in the medium and low-dose NMPCS groups. The levels of BUN in the high and low-dose NMPCS groups were decreased(P<0.05), and the levels of serum creatinine did not change in the administration groups. The positive drug group and the low, medium, and high-dose NMPCS groups significantly reduced the liver damage, with only a few hepatocytes vacuolization and a small number of red blood cells in the central venous area. The nephridial tissue structure was slightly abnormal, with a small number of red blood cell infiltration, and no obvious inflammatory cell infiltration was found in the glomerulus in these groups. No degeneration was found in renal tubular epithelial cells, with mild glomerular and tubular lesions and a small amount of sodium urate deposition and crystallization in the positive drug group and the low, medium, and high-dose NMPCS groups. The relative protein expressions of XOD in the positive drug group and the high dose NMPCS group were decreased(P<0.05), and the relative mRNA expressions of XOD in the positive drug group and the high and low-dose NMPCS groups were decreased as well(P<0.05). The above results show that NMPCS reduces uric acid in rats with HUA by regulating XOD, which provides a certain experimental basis for the development of NMPCS as a new medicine for the treatment of HUA.

Topics: Animals; Creatinine; Crocus; Hyperuricemia; Kidney; Kidney Diseases; Rats; Uric Acid; Xanthine Oxidase

Phellodendri Chinensis Cortex (PC) is a traditional medicinal material used to treat gout and hyperuricemia (HUA) in China. Berberine (BBR), the main component of PC, possesses anti-hyperuricemic and anti-gout effects. However, BBR exhibits low bioavailability due to its extensive metabolism and limited absorption. Thus, the metabolites of BBR are believed to be the potential active forms responsible for its in vivo biological activities. Berberrubine (BRB), one of the major metabolites of BBR, exhibits appreciable biological activities even superior to BBR. In this work, the anti-hyperuricemic efficacy of BRB was investigated in HUA model mice induced by co-administration with intraperitoneal potassium oxonate (PO) and oral hypoxanthine (HX) for 7 days. Results showed that administration with BRB (6.25, 12.5, and 25.0 mg/kg) significantly decreased the serum levels of uric acid (UA) by 49.70%, 75.35%, and 75.96% respectively, when compared to the HUA group. In addition, BRB sharply decreased the levels of blood urea nitrogen (BUN) (by 19.62%, 28.98%, and 38.72%, respectively) and serum creatinine (CRE) (by 16.19%, 25.07%, and 52.08%, respectively) and reversed the PO/HX-induced renal histopathological damage dose-dependently. Additionally, BRB lowered the hepatic XOD activity, downregulated the expressions of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1), upregulated expressions of organic anion transporter 1/3 (OAT1/3) and ATP-binding cassette transporter subfamily G member 2 (ABCG2) at both protein and mRNA levels, and suppressed the activation of the JAK2/STAT3 signaling pathway. In addition, BRB significantly decreased the levels of inflammatory mediators (IL-1β, IL-6, and TNF-α). In conclusion, our study indicated that BRB exerted anti-hyperuricemic effect, at least in part, via regulating the urate transporter expressions and suppressing the JAK2/STAT3 signaling pathway. BRB was believed to be promising for further development into a potential therapeutic agent for HUA treatment.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 2; Berberine; Blood Urea Nitrogen; Chemical and Drug Induced Liver Injury; Creatinine; Cytokines; Disease Models, Animal; Glucose Transport Proteins, Facilitative; Hyperuricemia; Hypoxanthine; Janus Kinase 2; Kidney Diseases; Male; Mice; Organic Anion Transport Protein 1; Organic Anion Transporters; Organic Anion Transporters, Sodium-Independent; Oxonic Acid; Protective Agents; Signal Transduction; STAT3 Transcription Factor; Uric Acid; Xanthine Oxidase

The present study was aimed to develop a novel sustained-release formulation for allopurinol (ALP/SR) with the use of a pH-sensitive polymer, hydroxypropyl methylcellulose acetate succinate, to reduce nephrotoxicity. ALP/SR was evaluated in terms of crystallinity, the dissolution profile, pharmacokinetic behavior, and nephrotoxicity in a rat model of nephropathy. Under acidic conditions (pH1.2), sustained release behavior was seen for ALP/SR, although both crystalline ALP and ALP/SR exhibited rapid dissolution at neutral condition. After multiple oral administrations of ALP samples (10 mg-ALP/kg) for 4 days in a rat model of nephropathy, ALP/SR led to a low and sustained plasma concentration of ALP, as evidenced by half the maximum concentration of ALP and a 2.5-fold increase in the half-life of ALP compared with crystalline ALP, possibly due to suppressed dissolution behavior under acidic conditions. Repeated-dosing of ALP/SR resulted in significant reductions in plasma creatinine and blood urea nitrogen levels by 73% and 69%, respectively, in comparison with crystalline ALP, suggesting the low nephrotoxic risk of ALP/SR. From these findings, a strategic SR formulation approach might be an efficacious dosage option for ALP to avoid severe nephrotoxicity in patients with nephropathy.

Topics: Administration, Oral; Allopurinol; Animals; Antineoplastic Agents; Blood Urea Nitrogen; Cisplatin; Creatinine; Delayed-Action Preparations; Drug Liberation; Gout Suppressants; Half-Life; Kidney; Kidney Diseases; Male; Methylcellulose; Rats, Sprague-Dawley

The study was designed to explore the effects of Withaferin A (WFA) on hyperuricemia-induced kidney injury and its action mechanism. Potassium oxonate (PO) was employed to establish the hyperuricemic mouse model. The pathological changes of renal tissue were evaluated by hematoxylin-eosin and masson trichrome staining. The levels of creatinine, blood urea nitrogen (BUN), uric acid (UA) and xanthine oxidase (XOD) were detected using corresponding commercial kits. Expressions of collagen-related and apoptosis-associated proteins in renal tissues were, respectively, evaluated by immunofluorescence and western blotting. Cell apoptosis was detected by TUNEL assay, and transporter expressions using western blotting. Followed by WFA, NRK-52E cells were treated with UA before evaluation of apoptosis and fibrosis. Results indicated that WFA ameliorated renal damage, improved kidney function, and decreased levels of creatinine, BUN, UA, and XOD in PO-induced hyperuricemic mice. Furthermore, WFA significantly prevented renal fibrosis and increased the expression of collagen-related proteins. Similarly, WFA markedly inhibited renal apoptosis, accompanied by changes of apoptosis-related proteins. Importantly, expression of transporters responsible for the secretion of organic anion transporter 1 (OAT1), OAT3, ATP-binding cassette subfamily G member 2 (ABCG2) was remarkably enhanced whereas that of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) was reduced in renal tissues of mice with hyperuricemia.

Topics: Animals; Apoptosis; Disease Models, Animal; Fibrosis; Hyperuricemia; Kidney; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Oxonic Acid; Withanolides; Xanthine Oxidase

Anti-Koch and HAART have been shown to independently induce toxicity to the liver and kidney, albeit available data are few and inconsistent. The present study evaluates the impact of Anti-Koch and HAART, when administered singly and in combination, on hepatic and renal status, and the possible role of adenine deaminase (ADA)/xanthine oxidase (XO) pathway. Anti-Koch and HAART administration were observed to independently impair hepatic and renal functions, diminish glutathione content, and substantially increase lipid peroxidation (MDA) and nitrogen reactive specie (NO). Coherently, these drugs caused significant accumulation of polymorphonuclear leucocytes, up-regulated ADA/XO signaling, increased uric acid production, and enhanced DNA fragmentation in the liver and kidney. Anti-Koch treatment did not significantly alter hepatic and renal levels of nitric oxide nor induce DNA fragmentation in the kidney. Co-administration of anti-Koch and HAART aggravated the observed biochemical alterations. Findings from the histopathological studies of the liver and renal tissues were in agreement with observed biochemical alterations. In conclusion, this report is the first to reveal that anti-Koch and HAART, when administered singly or in combination, attenuate glutathione content and elevate uric acid production in the liver and kidney via upregulation of ADA/XO signaling with resultant oxidative and nitrosative stress, and increased DNA fragmentation.

Topics: Aminohydrolases; Animals; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Chemical and Drug Induced Liver Injury; DNA Fragmentation; Glutathione; Kidney Diseases; Lipid Peroxidation; Male; Monocytes; Oxidative Stress; Rats; Rats, Wistar; Reactive Nitrogen Species; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Animals; Blood Urea Nitrogen; Flavanones; Flavonoids; Kidney Diseases; Liver; Mice; Molecular Docking Simulation; Uric Acid; Xanthine Oxidase

Although hyperuricemia has been shown to be associated with the progression of cardiovascular disorder and chronic kidney disease (CKD), there is conflicting evidence as to whether xanthine oxidase (XO) inhibitors confer organ protection besides lowering serum urate levels. In this study, we addressed the cardio-renal effects of XO inhibition in rodent CKD model with hyperuricemia. Sprague-Dawley rats underwent 5/6 nephrectomy and received a uricase inhibitor oxonic acid for 8 weeks (RK + HUA rats). In some rats, a XO inhibitor febuxostat was administered orally. Compared with control group, RK + HUA group showed a significant increase in albuminuria and renal injury. Febuxostat reduced serum uric acid as well as urinary albumin levels. Histological and immunohistochemical analysis of the kidney revealed that febuxostat alleviated glomerular, tubulointerstitial, and arteriolar injury in RK + HUA rats. Moreover, in the heart, RK + HUA showed individual myofiber hypertrophy and cardiac fibrosis, which was significantly attenuated by febuxostat. We found that renal injury and the indices of cardiac changes were well correlated, confirming the cardio-renal interaction in this model. Finally, NF-E2-related factor 2 (Nrf2) and the downstream target heme oxygenase-1 (HO-1) protein levels were increased both in the heart and in the kidney in RK + HUA rats, and these changes were alleviated by febuxostat, suggesting that tissue oxidative stress burden was attenuated by the treatment. These data demonstrate that febuxostat protects against cardiac and renal injury in RK + HUA rats, and underscore the pathological importance of XO in the cardio-renal interaction.

Topics: Animals; Cardiotonic Agents; Disease Models, Animal; Febuxostat; Heart; Hyperuricemia; Kidney Diseases; Kidney Function Tests; Male; Myocardium; Nephrectomy; Oxidative Stress; Oxonic Acid; Protective Agents; Rats, Sprague-Dawley; Xanthine Oxidase

This study examines correlations among serum proteins, clinical score, body weight and kidney function biomarkers after a standard treatment course (meglumine antimoniate plus allopurinol) in twelve Canine leishmaniosis (CanL) patients at the three times points pre treatment, after treatment and after the end of treatment. The laboratory variables measured were those used for the follow-up of sick dogs along with biomarkers of kidney function: glomerular filtration rate (GFR), creatinine (Cr), urea, calcium, inorganic phosphorus, urine specific gravity (USG) and urine protein to creatinine ratio (UPC). Arterial blood pressure (systolic blood pressure, SBP), clinical score (CS) and weight were also monitored over the study period. At Tp0, GFR was within the normal range in most dogs. Hyperfiltration was detected in three patients and hypofiltration in one. In dogs showing hyperfiltration, this factor remained in the non-azotemic range over the whole study period. After treatment normal filtration values were recovered. Meglumine antimoniate did not modify GFR or USG. A significant reduction in UPC was recorded. In all dogs, clinical scores improved. Negative correlation was found between GFR and Cr, UPC and albumin (Alb) and CS and Alb, while positive correlation was detected between UPC and total globulins (GlobT), CS and GlobT, UPC and total solids (TS), SBP and CS and SBP and UPC. Our findings indicate no impacts on kidney function of the treatment of CanL with meglumine antimoniate, as no effects were produced on GFR or USG. Treatment was effective and found to reduce UPC which could suggest improved glomerular injury.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Biomarkers; Creatinine; Dog Diseases; Dogs; Female; Glomerular Filtration Rate; Kidney Diseases; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine Antimoniate

Recent data suggested a causative role of uric acid (UA) in the development of renal disease, in which endothelial dysfunction is regarded as the key mechanism. Endothelial-to-mesenchymal transition (EndoMT) and shedding of the glycocalyx are early changes of endothelial dysfunction. We investigated whether UA induced EndoMT in HUVECs and an animal model of hyperuricemia fed with 2% oxonic acid for 4 wk. UA induced EndoMT in HUVECs with a generation of reactive oxygen species

Topics: Allopurinol; Animals; Cells, Cultured; Endothelium, Vascular; Glycocalyx; Gout Suppressants; Hyperuricemia; Kidney Diseases; Male; Oxidative Stress; Phenotype; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Uric Acid

Lesinurad (LESU) is a selective urate reabsorption inhibitor approved at 200 mg daily for use with a xanthine oxidase inhibitor (XOI) to treat hyperuricaemia in gout patients failing to achieve target serum urate on XOI. The aim of the study was to investigate the long-term safety of LESU + XOI therapy.. Safety data were pooled from three 12-month phase III (core) trials evaluating LESU 200 and 400 mg/day combined with an XOI (LESU200+XOI and LESU400+XOI), and two 12-month extension studies using descriptive statistics. To adjust for treatment duration, treatment-emergent adverse events (TEAEs) were expressed as exposure-adjusted incidence rates (patients with events per 100 person-years).. In the core studies, exposure-adjusted incidence rates for total and total renal-related TEAEs were comparable for XOI alone and LESU200+XOI but higher with LESU400+XOI. Exposure-adjusted incidence rates for serum creatinine (sCr) elevations ⩾1.5×baseline were 2.9, 7.3 and 18.7, respectively. Resolution (sCr ⩽1.2×baseline) occurred in 75-90% of all events, with 66-75% occurring without any study medication interruption. Major adverse cardiovascular events were 3, 4 and 9 with XOI, LESU200+XOI and LESU400+XOI, respectively. Longer exposure in core+extension studies did not increase rates for any safety signals.. At the approved dose of 200 mg once-daily combined with an XOI, LESU did not increase renal, cardiovascular or other adverse events compared with XOI alone, except for sCr elevations. With extended exposure in the core+extension studies, the safety profile was consistent with that observed in the core studies, and no new safety concerns were identified.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Clinical Trials, Phase III as Topic; Drug Therapy, Combination; Enzyme Inhibitors; Female; Gout; Gout Suppressants; Humans; Kidney Diseases; Male; Middle Aged; Randomized Controlled Trials as Topic; Thioglycolates; Treatment Outcome; Triazoles; Uric Acid; Xanthine Oxidase; Young Adult

Hyperuricemia has been identified as an independent risk factor for chronic kidney disease (CKD) and is associated with the progression of kidney diseases. It remains unknown whether enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, can regulate metabolism of serum uric acid and progression of renal injury induced by hyperuricemia. In this study, we demonstrated that blockade of EZH2 with 3-DZNeP, a selective EZH2 inhibitor, or silencing of EZH2 with siRNA inhibited uric acid-induced renal fibroblast activation and phosphorylation of Smad3, epidermal growth factor receptor (EGFR), and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in cultured renal fibroblasts. Inhibition of EZH2 also suppressed proliferation of renal fibroblasts and epithelial-mesenchymal transition of tubular cells. In a mouse model of renal injury induced by hyperuricemia, EZH2 and trimethylation of histone H3 at lysine27 expression levels were enhanced, which was coincident with renal damage and increased expression of lipocalin-2 and cleaved caspase-3. Inhibition of EZH2 with 3-DZNeP blocked all these responses. Furthermore, 3-DZNeP treatment decreased the level of serum uric acid and xanthine oxidase activity, alleviated renal interstitial fibrosis, inhibited activation of transforming growth factor-β/Smad3, EGFR/ERK1/2, and nuclear factor-κB signaling pathways, as well as reduced expression of multiple chemokines/cytokines. Collectively, EZH2 inhibition can reduce the level of serum uric acid and alleviate renal injury and fibrosis through a mechanism associated with inhibition of multiple signaling pathways. Targeting EZH2 may be a novel strategy for the treatment of hyperuricemia-induced CKD.

Topics: Animals; DNA Methylation; Enhancer of Zeste Homolog 2 Protein; Fibroblasts; Fibrosis; Histones; Hyperuricemia; Kidney Diseases; Mice; Mitogen-Activated Protein Kinase 3; Phosphorylation; RNA, Small Interfering; Signal Transduction; Smad3 Protein; Transforming Growth Factor beta; Uric Acid; Xanthine Oxidase

Uric acid nephropathy (UAN) is one of the most common metabolic diseases and leads to kidney damage. This study aimed to evaluate the effect of Weicao capsule on renal injury of UAN rats and to examine whether the mechanism was associated with induction of autophagy and degradation of nucleotide binding oligomerization domain (Nod)-like receptor (NLR) protein 3 (NLRP3) inflammasome. Sixty Sprague-Dawley rats were randomly allocated into 6 groups: Control, Model, Allopurinol, and Weicao (0.55/1.1/2.2 g/kg) group. The data showed activation of renal NLRP3 inflammasome in UAN rats, with elevation in serum levels of interleukin (IL)-1β and IL-18, and subsequent deterioration of renal injury. Fortunately, Weicao had a markedly therapeutic effect on UAN rats, including improving renal function-related indexes, ameliorating hyperuricemia-related inflammation, decreasing crystals in renal tissue and alleviating renal interstitial fibrosis. Additionally, Weicao exerted anti-proliferative and anti-apoptosis effects on rat renal tubular epithelial cell NRK-52E in macrophages from UAN rats. Our investigation into the mechanism revealed that Weicao suppressed the activated NLRP3 inflammasome. Furthermore, Weicao induced autophagy, as evidenced by a dose-dependent increase in levels of renal autophagy-related proteins in UAN rats. Moreover, autophagy inhibitor 3-MA and NLRP3 activator ATP blocked the effect of Weicao on autophagy induction and NLRP3 inflammasome degradation. In conclusion, Weicao had similar effects as allopurinol and exerted anti-inflammatory and renal-protective effect in a concentration-dependent manner in UAN rats, most likely through increasing autophagy and NLRP3 degradation. Our study provides new insight into the underlying mechanism of Weicao in the treatment of UAN.

Topics: Allopurinol; Animals; Autophagy; Cell Line; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Kidney; Kidney Diseases; NLR Family, Pyrin Domain-Containing 3 Protein; Proteolysis; Rats; Rats, Sprague-Dawley; Uric Acid

Renal disease is considered the main cause of natural mortality in dogs with canine leishmaniosis. The pathological mechanisms associated with kidney injury in canine leishmaniosis include immune complex glomerulonephritis, tubulointerstitial nephritis and occasionally renal amyloidosis. Proteinuria is a frequent finding in canine leishmaniosis and its quantification by the urine protein-creatinine ratio (UPC) is an important parameter in the staging of canine lesihmaniosis as presented by the LeishVet group.. A 4.5 year-old spayed female Belgian Malinois dog was presented to the Hebrew University Veterinary Teaching hospital with epistaxis and rhinitis and diagnosed also with proteinuria and acute kidney injury (AKI IRIS grade V) associated with canine leishmaniosis that developed to LeishVet stage III with chronic kidney disease (CKD) after stabilization. Clinicopathologic abnormalities included azotemia with a peak creatinine concentration of 7.76 mg/dl (reference interval, 0.3-1.2 ng/dl), hypoalbuminemia (1.76 g/dl, reference interval 3-4.4 g/dl), hyperglobulinemia (4.54 g/dl, reference interval 1.8-3.9 g/dl) and proteinuria (urine protein/creatinine ratio 15.6, normal < 0.2). Serology by the enzyme-linked immunosorbent assay (ELISA) for Leishmania infantum was positive with high antibody levels. The dog was hospitalized and treated with intermittent hemodialysis, feeding through an esophageal feeding tube, medical treatment for protein losing nephropathy and antileishmanial treatment with allopurinol. Kidney function gradually improved and the dog's creatinine levels and proteinuria decreased until complete normalization two years after the acute insult. However, rhinitis and sneezing persisted and although the anti-leishmanial antibodies decreased over time, the dog remains constantly seropositive.. To our knowledge, this is the first report of hemodialysis management of AKI associated with canine leishmaniosis. Hemodialysis was imperative in stabilizing the dog's renal disease and controlling its azotemia. It demostrates that hemodialysis can be beneficial in the management of acute deterioration of kidney disease in canine leishmaniosis.

Topics: Acute Kidney Injury; Allopurinol; Animals; Antiprotozoal Agents; Creatinine; Disease Management; Dog Diseases; Dogs; Epistaxis; Kidney Diseases; Leishmania infantum; Leishmaniasis; Proteinuria; Renal Dialysis

An epidemic of chronic kidney disease (CKD) has been observed in Central America among workers in the sugarcane fields. One hypothesis is that the CKD may be caused by recurrent heat stress and dehydration, and potentially by hyperuricemia. Accordingly, we developed a murine model of kidney injury associated with recurrent heat stress. In the current experiment, we tested whether treatment with allopurinol (a xanthine oxidase inhibitor that reduces serum urate) provides renal protection against recurrent heat stress and dehydration. Eight-week-old male C57BL/6 mice were subjected to recurrent heat stress (39.5°C for 30 min, 7 times daily, for 5 wk) with or without allopurinol treatment and were compared with control animals with or without allopurinol treatment. Mice were allowed ad libitum access to normal laboratory chow (Harlan Teklad). Kidney histology, liver histology, and renal function were examined. Heat stress conferred both kidney and liver injury. Kidneys showed loss of proximal tubules, infiltration of monocyte/macrophages, and interstitial collagen deposition, while livers of heat-stressed mice displayed an increase in macrophages, collagen deposition, and myofibroblasts. Allopurinol provided significant protection and improved renal function in the heat-stressed mice. The renal protection was associated with reduction in intrarenal uric acid concentration and heat shock protein 70 expression. Heat stress-induced renal and liver injury can be protected with allopurinol treatment. We recommend a clinical trial of allopurinol for individuals developing renal injury in rural areas of Central America where the epidemic of chronic kidney disease is occurring.

Topics: Allopurinol; Animals; Collagen; Disease Models, Animal; Enzyme Inhibitors; Heat Stress Disorders; Hot Temperature; HSP70 Heat-Shock Proteins; Hyperthermia, Induced; Kidney; Kidney Diseases; Liver; Liver Diseases; Male; Mice, Inbred C57BL; Uric Acid; Xanthine Oxidase

Hyperuricemia is associated with the development of chronic kidney disease. Epithelial-to-mesenchymal transition (EMT) induced by hyperuricemia is blamed for initiation of renal fibrosis, which is one of the main characters of hyperuricemic nephropathy. Qi-Zhu-Xie-Zhuo-Fang (QZXZF) has been employed clinically for many years to treat patients with hyperuricemic nephropathy, but the mechanism underlying the therapeutic potential remains unclear. In the present study, QZXZF was applied to rats treated with adenine (100mg/kg) and potassium oxonate (300mg/kg) and biochemical estimations, morphology and immunohistochemistry were performed to investigate whether QZXZF can improve hyperuricemia induced renal fibrosis and to explore the possible mechanisms. We found QZXZF significantly reduced serum uric acid, cystatinC and hepatic xanthine oxidase (XO) activities, meanwhile improved renal histopathologic changes of hyperuricemic nephropathy rats. Furthermore, QZXZF not only substantially decreased the protein levels of fibronectin and Collagen I but also downregulated E-cadherin and upregulated α-SMA in the kidneys of hyperuricemic nephropathy rats. In conclusion, QZXZF reduced serum uric acid levels and protected kidney against fibrosis in potassium oxonate and adenine induced hyperuricemic nephropathy rats. The mechanism might be associated with the inhibition of hepatic XO activity and the renal epithelial-to-mesenchymal transition.

Topics: Animals; Collagen; Disease Progression; Down-Regulation; Drugs, Chinese Herbal; Extracellular Matrix; Fibrosis; Hyperuricemia; Kidney; Kidney Diseases; Kidney Tubules; Male; Neuroprotective Agents; Phenotype; Rats, Wistar; Transcription Factors; Uric Acid; Xanthine Oxidase

To assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in elderly.. In a retrospective cohort study using 2006-2012 Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 183 days without either medication). We used 5:1 propensity-matched Cox regression analyses to compare the HR of incident renal disease with allopurinol use (and dose) versus febuxostat (reference). Sensitivity analyses included multivariable-adjusted regression models.. There were 31 465 new allopurinol or febuxostat treatment episodes in 26 443 patients; 8570 ended in incident renal disease. Crude rates of incident renal disease per 1000 person-years were 192 with allopurinol versus 338 with febuxostat. Crude rates of incident renal disease per 1000 person-years were lower with higher daily dose: allopurinol <200, 200-299 and ≥300 mg/day with 238, 176 and 155; and febuxostat 40 and 80 mg/day with 341 and 326, respectively. In propensity-matched analyses, compared with febuxostat, allopurinol use was associated with lower HR of incident renal disease, 0.61 (95% CI 0.49 to 0.77). Compared with febuxostat 40 mg/day, allopurinol doses <200, 200-299 and ≥300 mg/day were associated with lower HR of incident renal disease, 0.75 (95% CI 0.65 to 0.86), 0.61 (95% CI 0.52 to 0.73) and 0.48 (95% CI 0.41 to 0.55), respectively. Sensitivity analyses using multivariable-adjusted regression confirmed these findings.. Allopurinol was associated with a lower risk of incident renal disease in elderly patients than febuxostat. Future studies need to examine the mechanism of this potential renal benefit of allopurinol.

Topics: Administrative Claims, Healthcare; Aged; Aged, 80 and over; Allopurinol; Comparative Effectiveness Research; Febuxostat; Female; Gout; Gout Suppressants; Humans; Incidence; Kidney Diseases; Male; Medicare; Propensity Score; Proportional Hazards Models; Retrospective Studies; United States

We examined the roles of xanthine oxidoreductase (XOR) in renal ischemia reperfusion (IR) injury.. XOR+/+ and XOR+/- mice were subjected to 24-h reperfusion after a 45-min bilateral renal artery occlusion or sham operation. We evaluated the renal damage based on the concentrations of blood urea nitrogen (BUN) and serum creatinine (Cr), and histological changes were detected by PAS staining. Xanthine dehydrogenase, oxidase (XO) and XOR activities, amounts of blood and urine 8-OHdG, and expressions of TNF-α and MCP-1 mRNA were examined. F4/80 and nitrotyrosine-positive cells were assessed by immunohistochemical staining.. The BUN and Cr concentrations in the XOR+/+IR mice were increased significantly compared to those in XOR+/-IR and allopurinol-treated XOR+/+IR mice. XO and XOR activity, which were increased in IR mice, were reduced in the allopurinol-treated XOR+/+IR and XOR+/-IR mice compared to the XOR+/+IR mice. The concentrations of blood and urine 8-OHdG, and the expressions of MCP-1 and TNF-α mRNA were increased significantly in the XOR+/+IR mice compared to those in the XOR+/-IR mice. The histological analysis revealed that the XOR+/-IR and allopurinol-treated XOR+/+IR mice showed less tubular injury than the XOR+/+IR mice in the cortex regions, with the reduction of inflammation and oxidative stress assessed by the immunohistological staining for F4/80 and nitrotyrosine.. Both the disruption of XOR gene in XOR+/- mice and the reduction of XOR activity in allopurinol-treated XOR+/+IR mice attenuated renal tissue injury in this IR model. Reduced XOR activity during renal IR could be a beneficial treatment target.

Topics: Allopurinol; Animals; Blood Urea Nitrogen; Creatinine; Disease Models, Animal; Enzyme Inhibitors; Inflammation; Kidney Diseases; Male; Mice; Mice, Knockout; Oxidative Stress; Reperfusion Injury; Xanthine Dehydrogenase

Superoxide, nitric oxide (NO), and peroxynitrite are important mediators in the pathogenesis of ischemia-reperfusion (I/R) injury. We tested the renoprotective effects of allopurinol (ALP), a xanthine oxidase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), and 5,10,15,20-tetrakis (N-methyl-4-pyridyl) porphyrinato iron (III) (FeTMPyP) by selective inhibition of superoxide, NO, and peroxynitrite, respectively.. Male Sprague-Dawley rats were randomly assigned to 5 groups (n = 6 per group). Group 1 was a sham-operated group. Group 2 was the renal I/R group (30-minute ischemia followed by 24-hour reperfusion). Rats in groups 3, 4, and 5 received ALP, L-NAME, or FeTMPyP, respectively, at 5 minutes before the reperfusion. Serum creatinine (Cr), blood urea nitrogen (BUN), renal tissue malondialdehyde, superoxide dismutase, histological changes, apoptosis, and monocyte infiltration were evaluated. In addition, the combined treatment with ALP and L-NAME was compared with FeTMPyP in a second independent experiment.. The administration of ALP, L-NAME, and FeTMPyP diminished the increase in Cr (P = .0066 for all) and BUN (P = .0066 for ALP; and P = .013 for L-NAME) induced by I/R injury and decreased the histological damage (P = .0066 for all). In addition, ALP, L-NAME, and FeTMPyP attenuated the oxidative stress response as determined by a decrease in malondialdehyde level (P = .0066 for all), apoptotic renal tubular cells (P = .0066 for all), and monocyte infiltration (P = .0066 for all). The combined treatment of ALP and L-NAME decreased Cr and BUN levels to a greater degree than FeTMPyP (P = .016 for Cr; P = .0079 for BUN).. Superoxide, NO, and peroxynitrite are involved in renal I/R injury. The reduction of peroxynitrite formation, via inhibition of superoxide or NO, or the induction of peroxynitrite decomposition may be beneficial in renal I/R injury.

Topics: Allopurinol; Animals; Antioxidants; Apoptosis; Blood Urea Nitrogen; Creatinine; Cytoprotection; Disease Models, Animal; Enzyme Inhibitors; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Metalloporphyrins; Monocytes; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress; Peroxynitrous Acid; Rats, Sprague-Dawley; Reperfusion Injury; Superoxides; Xanthine Oxidase

The objective of this study was to evaluate and compare the evolution of the profile currently recommended by the International Renal Interest Society (IRIS) (sCr, UPC and sSDMA) with a panel of other different kidney biomarkers during treatment for canine leishmaniosis. This panel included three urinary glomerular biomarkers (uIgG, uCRP and uferritin) and three urinary tubular biomarkers (uGGT, uNAG and uRBP). These biomarkers were measured in two groups of dogs with canine leishmaniosis at IRIS stage I. Group 1: dogs showing proteinuria (UPC > 0.5) before treatment which did not decrease after treatment; Group 2: dogs showing proteinuria before treatment which decreased after treatment.. Group 1 showed no significant changes in any biomarker after treatment. In group 2, among the biomarkers recommended by the IRIS, only UPC showed a significant decrease after treatment. However all biomarkers of glomerular damage showed a significant decrease after treatment, with uIgG/Cr and uCRP/Cr showing the greater decreases. In addition uRBP/Cr and uNAG/Cr showed significant decreases after treatment.. In dogs with leishmaniosis at IRIS stage I that reduced UPC after treatment, there were no significant changes in serum creatinine and sSDMA. However, all the urine biomarkers evaluated with exception of uGGT showed a significant decrease. These decreases were more evident in those markers related with glomerular function, being uIgG/Cr the biomarker more associated with UPC. Further studies involving a larger number of animals and histological analysis of the kidney would be recommended to confirm these findings and evaluate the routine practical use of these urine biomarkers in canine leishmaniosis.

Topics: Allopurinol; Animals; Antimetabolites; Antiprotozoal Agents; Biomarkers; Dog Diseases; Dogs; Drug Therapy, Combination; Kidney Diseases; Leishmaniasis; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Proteinuria

To explore the effects of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi compatibility (PR) on uric acid metabolism and the expression of urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in rats with hyperuricemia.. Seventy male Sprague Dawley (SD) rats were randomly divided into 7 groups with 10 rats per group, including the normal group, model group, allopurinol group, benzbromarone group and PR groups at 3 doses (3.5, 7, 14 g/kg). Except the normal group, rats of the other groups were intragastrically administered 100 mg/kg hypoxanthine and 250 mg/kg ethambutol, and subcutaneously injected with 200 mg/kg potassium oxonate. All rats were continuously modeled for 17 days, and gavaged with corresponding drugs. The rats of the normal and model groups were gavaged with saline, once a day, for 2 weeks. The levels of serum uric acid (SUA), blood urea nitrogen (BUN) and creatinine (Cr) were determined. In addition, the contents of NGAL and KIM-1 in urine and the mRNA and protein expressions of xanthine oxidase (XOD) in liver of hyperuricemia rats were measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. Moreover, the pathological changes of kidney were analyzed by hematoxylin and eosin (HE) stain method.. Compared with the normal group, the levels of SUA, BUN, NGAL and KIM-1 and the expressions of hepatic XOD mRNA and protein in the hyperuricemia rats were increased signifificantly (P<0.01). PR signifificantly decreased the levels of SUA, BUN, NGAL and KIM-1 and down-regulated the mRNA and protein expressions of hepatic XOD (P<0.05 or P<0.01). In addition, the pathological changes of kidney were signifificantly suppressed by oral administration of PR.. PR ameliorated uric acid metabolism and protected renal function, the underlying mechanism was mediated by decreasing the levels of SUA, BUN, NGAL and KIM-1, inhibiting the expression of hepatic XOD and ameliorating the pathological change of kidney.

Topics: Animals; Blood Urea Nitrogen; Cell Adhesion Molecules; Creatinine; Drugs, Chinese Herbal; Hyperuricemia; Kidney; Kidney Diseases; Lipocalin-2; Male; Rats, Sprague-Dawley; RNA, Messenger; Uric Acid; Xanthine Oxidase

Cisplatin is an effective chemotherapeutic agent successfully used in the treatment of a wide range of solid tumors, while its usage is limited due to its nephrotoxicity. The present study was undertaken to examine the effectiveness of ginseng to ameliorate the renal nephrotoxicity, damage in kidney genomic DNA, tumor necrosis factor-α, interleukin 6, tumor suppressor P53, histological changes and oxidative stress induced by cisplatin in rats. Cisplatin caused renal damage, including DNA fragmentation, upregulates gene expression of tumor suppressor protein p53 and tumor necrosis factor-α and IL-6. Cisplatin increased the levels of kidney TBARS, xanthine oxidase, nitric oxide, serum urea and creatinine. Cisplatin decreased the activities of antioxidant enzymes (GST, GPX, CAT and SOD), ATPase and the levels of GSH. A microscopic examination showed that cisplatin caused kidney damage including vacuolization, severe necrosis and degenerative changes. Ginseng co-treatment with cisplatin reduced its renal damage, oxidative stress, DNA fragmentation and induced DNA repair processes. Also, ginseng diminished p53 activation and improved renal cell apoptosis and nephrotoxicity. It can be concluded that, the protective effects of ginseng against cisplatin induced-renal damage was associated with the attenuation of oxidative stress and the preservation of antioxidant enzymes.

Topics: Adenosine Triphosphatases; Animals; Apoptosis; Catalase; Cisplatin; Creatinine; DNA Fragmentation; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Interleukin-6; Kidney; Kidney Diseases; Male; Nitric Oxide; Oxidative Stress; Panax; Plant Preparations; Rats; Rats, Sprague-Dawley; Serum Albumin; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha; Tumor Suppressor Protein p53; Up-Regulation; Urea; Xanthine Oxidase

To investigate whether uric acid could regulate urate transporter 1 (URAT1) protein and activity level, we established uric acid nephropathy (UAN) rat model and detected their serum uric acid and URAT1 level with or without the treatment of allopurinol. Results here showed that allopurinol could reduce serum uric acid level in UAN rat model. We further found that in UAN rats, the total and surface URAT1 expression level were both increased while this increase could be blocked by allopurinol treatment. By treating URAT1 stable expressed HEK cell with monosodium urate (MSU) crystals, we found that URAT1 level showed an increase in both total and cell surface level, and it would colocalize more with Rab11 instead of Rab7. Consistently, we also found that the total URAT1 protein level will show an increase in the presence of lysosome inhibitors but not ubiquitin-proteasome inhibitors. Furthermore, we also found that MSU crystal could drive Numb, a clathrin-coated adaptor protein which performs a key function in cell division, out of cell surface and disassociated it from URAT1. Finally, we found that Numb short hairpin RNA (shRNA)-transfected showed a phenocopy as MSU treatment, while Numb-2A mutation over-expression could resist crystal-induced phenotypes. These findings indicated that uric acid crystal could increase URAT1 membrane distribution through inhibiting Numb-induced URAT1 lysosome degradation.

Topics: Allopurinol; Animals; Anion Transport Proteins; Cell Line; Disease Models, Animal; Endocytosis; Intracellular Signaling Peptides and Proteins; Kidney Diseases; Lysosomes; Male; Rats, Sprague-Dawley; Uric Acid

Allopurinol, a first-line drug used for treating gout, is increasingly prescribed worldwide to patients with asymptomatic hyperuricemia and comorbid renal or cardiovascular diseases. Nevertheless, allopurinol use has been associated with fatal hypersensitivity reactions, including drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The overall risks of allopurinol use remain unclear.. To investigate the incidence of, risk factors for, and mortality associated with allopurinol hypersensitivity in new users of allopurinol.. A retrospective nationwide population study was conducted using data from the Taiwan National Health Insurance Research Database, which includes detailed medical records of more than 23 million insured enrollees. Data were collected from January 1, 2005, through December 31, 2011, using the Anatomical Therapeutic Chemical classification system and International Classification of Diseases, Ninth Revision, Clinical Modification codes. Among 1,613,719 patients receiving allopurinol prescriptions, 495,863 were identified as new users.. Allopurinol hypersensitivity was identified within 3 months since the first prescription. The period for measuring related hospitalizations was 1 month since the episode, and the period for measuring renal complications or mortality was 2 months since the episode. Poisson regression test and multivariable logistic regression analysis were performed, and P < .01 was considered statistically significant.. Among the more than 23 million insured enrollees, the annual incidence rates were 4.68 per 1000 new users for allopurinol hypersensitivity, 2.02 per 1000 new users for related hospitalization, and 0.39 per 1000 new users for related mortality. The annual incidence of allopurinol hypersensitivity rose statistically significantly during the study period (P < .001). Risk factors for allopurinol hypersensitivity included female sex, age 60 years or older, initial allopurinol dosage exceeding 100 mg/d, renal or cardiovascular comorbidities, and use for treating asymptomatic hyperuricemia. Patients with asymptomatic hyperuricemia and renal or cardiovascular diseases had statistically significantly increased risk of allopurinol hypersensitivity (odds ratio [OR], 1.61; 95% CI, 1.33-1.94; P < .001 for renal diseases and OR, 1.52; 95% CI, 1.19-1.93; P < .001 for cardiovascular diseases). They also had statistically significantly increased risk of mortality (OR, 5.59; 95% CI, 2.61-11.94; P < .001 for renal diseases and OR, 3.57; 95% CI, 2.31-5.51; P < .001 for cardiovascular diseases).. The use of allopurinol in patients with asymptomatic hyperuricemia accompanied by renal or cardiovascular diseases statistically significantly increased the risk of hypersensitivity reactions. Physicians should be cautious when prescribing allopurinol to high-risk populations and should consider the potential risks of fatal adverse reactions.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Cardiovascular Diseases; Child; Child, Preschool; Drug Hypersensitivity; Female; Gout Suppressants; Hospitalization; Humans; Hyperuricemia; Incidence; Infant; Kidney Diseases; Male; Middle Aged; Retrospective Studies; Risk Factors; Taiwan; Young Adult

We report 2 cases of familial juvenile hyperuricemic nephropathy, a rare autosomal dominant disorder characterized by uromodulin gene mutations leading to hyperuricemia secondary to profound renal uric acid underexcretion, gout, and chronic renal disease. Case 1 involves a 56-year-old woman who underwent a kidney transplant after steady decline in kidney function since the age of 19 years. Her gout had been successfully controlled with varying doses of daily allopurinol. Case 2, the son of case 1, presented with already progressive and debilitating arthritis at the age of 34 years with relatively stable chronic renal failure that was also subsequently managed with daily allopurinol and judicious anti-inflammatory prophylaxis.

Topics: Adult; Allopurinol; Arthritis, Gouty; Diagnosis, Differential; Disease Progression; Female; Follow-Up Studies; Gout; Graft Survival; Humans; Hyperuricemia; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Pedigree; Sampling Studies; Severity of Illness Index; Treatment Outcome

Increased serum uric acid has been considered a cardiovascular risk factor but no study has assessed its relation with hospital mortality or length of stay. On the basis of data obtained from a prospective registry, the prevalence of gout/hyperuricemia and its association with these and other clinical parameters was evaluated in an Italian cohort of elderly patients acutely admitted to internal medicine or geriatric wards.. While the prevalence of gout was calculated by counting patients with this diagnosis hyperuricemia was inferred in patients taking allopurinol at hospital admission or discharge, on the assumption that this drug was only prescribed owing to the finding of high serum levels of uric acid. A series of clinical and demographic variables were evaluated for their association with gout/hyperuricemia.. Of 1380 patients, 139 (10%) had a diagnosis of gout or were prescribed allopurinol. They had more co-morbidities (7.0 vs 5.6; P<0.0001) and consumed more drugs (6.8 vs 5.0; P<0.0001). The CIRS (co-morbidity index) was worse in these patients (OR 1.28 95% CI 1.15-1.41). Multivariable regression analysis showed that only renal and heart failures were independently associated with gout/allopurinol intake. Moreover, this combined event was associated with an increased risk of adverse events during hospitalization (OR 1.66, 95% CI 1.16-2.36), but not with the risk of re-hospitalization, length of hospital stay or death.. Gout/allopurinol intake has a high prevalence in elderly patients acutely admitted to hospital and are associated with renal and cardiovascular diseases, an increased rate of adverse events and a high degree of drug consumption. In contrast, this finding did not affect the length of hospitalization nor hospital mortality.

Topics: Age Factors; Aged; Aged, 80 and over; Allopurinol; Cardiovascular Diseases; Chronic Disease; Comorbidity; Female; Gout; Hospital Mortality; Hospitalization; Humans; Hyperuricemia; Kidney Diseases; Length of Stay; Male; Treatment Outcome; Uric Acid

To assess application of cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) as biomarkers for renal ischemic injury. We also evaluated the use of allopurinol as a renoprotective agent. A second goal was to assess cystatin C as a biomarker in patients undergoing partial nephrectomy.. Using 58 Sprague-Dawley rats, we evaluated urinary cystatin C (n=26) and NGAL (n=32) as a biomarker for renal ischemia injury. Half of the rats were pretreated with allopurinol; the other cohort served as a control. The right renal hilum was ligated in all rats, thereby creating a solitary kidney model. After a 30-minute stabilization period, the left hilum was clamped for time periods of 15, 30, and 60 minutes. Urinary levels of cystatin C and NGAL were then measured at the following time points: Preclamp (after the 30-minute stabilization period) and postclamp (30, 45, and 60 minute periods after unclamping). For our clinical subjects, serum cystatin C levels (n=17) were obtained preoperatively, at the induction of anesthesia before robot-assisted partial nephrectomy, immediately postoperatively, and on postoperative days 1 and 2. Three of these patients had their tumors excised off clamp and served as controls. We then estimated glomerular filtration rate by using the Creatinine-Cystatin C Equation.. Urinary levels of cystatin C and NGAL increased after renal clamping. The 30-minute period of ischemia demonstrated the greatest increase of these biomarkers. Allopurinol did appear to serve a renoprotective function in those animals undergoing 30-minute clamp times. In our clinical patients, the serum cystatin C levels did increase at each postoperative time point, but remained nonelevated in the control group.. Cystatin C and NGAL both appear to be useful biomarkers of renal injury. Studies with larger numbers are needed, however. Also, allopurinol does exhibit renoprotective effects against ischemic injury.

Topics: Acute-Phase Proteins; Allopurinol; Animals; Biomarkers; Case-Control Studies; Creatinine; Cystatin C; Disease Models, Animal; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Lipocalin-2; Lipocalins; Male; Proto-Oncogene Proteins; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Time Factors

A series of studies have recently demonstrated that the oxidative stress, nuclear factor-kappa B (NF-κB) activation and the subsequent coordinated inflammatory responses played an important role in the pathogenesis of urate nephropathy (UN). Polydatin has been suggested to have the properties of anti-oxidative, anti-inflammatory and nephroprotective effects. However, the possible protective and beneficial effects of polydatin on UN are not fully elucidated. Therefore, we investigated the potential beneficial effects and possible mechanisms of polydatin on UN. In this study, polydatin showed inhibitory activities on xanthine oxidase to repress the level of serum uric acid in vivo and in vitro. Further investigations revealed that polydatin displayed little toxic effects and significantly ameliorated the renal function in fructose-induced UN mice. The nephroprotective activities of polydatin was not only due to the effects on remarkably attenuating the oxidative stress induced by uric acid, but also on markedly suppressing the oxidative stress-related inflammatory cascade, including decreasing the expressions of NF-κB p65, COX-2 and iNOS proteins and inhibiting the productions of TNF-α, PGE(2) and IL-1β. These findings elucidated that polydatin exhibited prominent nephroprotective activities and low toxic effects.

Topics: Animals; Blood Chemical Analysis; Body Weight; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Drugs, Chinese Herbal; Fructose; Glucosides; Inflammation; Interleukin-1beta; Kidney; Kidney Diseases; Male; Mice; Mice, Inbred Strains; NF-kappa B; Nitric Oxide Synthase Type II; Oxidative Stress; Protective Agents; Stilbenes; Tumor Necrosis Factor-alpha; Uric Acid; Xanthine Oxidase

Hyperuricemia frequently complicates cyclosporine (CsA) therapy. Previous studies have shown that hyperuricemia exacerbates interstitial and vascular lesions in the cyclosporine model. We tested the hypothesis that normalization of uric acid could prevent the development of cyclosporine toxicity.. CsA nephropathy was induced by administering CsA (15 mg/kg/day) for 7 weeks to rats on a low salt diet (CsA group). The effect of preventing hyperuricemia was determined by concomitant treatment with a xanthine oxidase inhibitor, allopurinol (CsAALP), or with a uricosuric, benzbromarone (CsABENZ), in drinking water. Control groups included vehicle-treated rats.. CsA-treated rats developed mild hyperuricemia with arteriolar hyalinosis, tubular atrophy, striped interstitial fibrosis, increased cell proliferation and decreased VEGF expression. Treatment with allopurinol or benzbromarone limited renal disease, with reduced interstitial fibrosis, cell proliferation, macrophage infiltration, osteopontin expression and arteriolar hyalinosis, in association with restoration of VEGF expression. Both drugs provided comparable protection.. An increase in uric acid exacerbates CsA nephropathy in the rat. Concomitant treatment with allopurinol or benzbromarone reduced the severity of renal disease. The similar protection observed with both drugs suggests that the effect is associated more with lowering uric acid levels than the antioxidant effect of allopurinol.

Topics: Allopurinol; Animals; Benzbromarone; Cell Proliferation; Cyclosporine; Enzyme Inhibitors; Fibrosis; Hyperuricemia; Immunohistochemistry; Kidney; Kidney Diseases; Male; Osteopontin; Random Allocation; Rats; Rats, Sprague-Dawley; Uric Acid; Uricosuric Agents; Vascular Endothelial Growth Factor A; Xanthine Oxidase

Renal interstitial fibrosis is the common pathway in progressive renal diseases, where oxidative stress promotes inflammation and macrophage infiltration. Febuxostat is a novel nonpurine xanthine oxidase (XO)-specific inhibitor for treating hyperuricemia. While some reports suggest a relationship between hyperuricemia and chronic kidney disease (CKD), the renoprotective mechanism of an XO inhibitor in CKD remains unknown. Recent reports have focused on XO as a source of oxidative stress.. Here, we investigate the potential of febuxostat to reduce fibrogenic and inflammatory responses in an established interstitial fibrosis model-unilateral ureteric obstruction (UUO). Male Sprague-Dawley rats were divided into three groups: sham-operated group, vehicle-treated UUO group, and febuxostat-treated UUO group.. Treatment with febuxostat diminished XO activity in obstructed kidneys, and suppressed nitrotyrosine, a marker of oxidative stress. Consequently, febuxostat inhibited early proinflammatory cytokine expression, followed by a reduction of interstitial macrophage infiltration. In addition, febuxostat suppressed transforming growth factor-β messenger RNA expression, thereby ameliorating smooth muscle alpha actin and type I collagen expression.. Our results provide evidence for the renoprotective action of febuxostat against the formation of interstitial fibrosis. A decrease in macrophage infiltration and interstitial fibrosis, along with a decrease of the oxidative stress marker, strongly suggests the existence of a causal relationship between them. Febuxostat may have therapeutic value in slowing or preventing interstitial fibrosis in patients with CKD.

Topics: Animals; Cell Movement; Cytokines; Disease Models, Animal; Febuxostat; Fibrosis; Kidney; Kidney Diseases; Macrophages; Male; Nephritis, Interstitial; Oxidative Stress; Rats; Rats, Sprague-Dawley; Thiazoles; Transforming Growth Factor beta; Ureteral Obstruction; Xanthine Oxidase

Cisplatin-induced nephrotoxicity is the main cause for its dose-limited use in the treatment of various cancers and results in acute renal cell injury through generation of reactive oxygen species. Chrysin possess antioxidant, anti-inflammatory and anti-cancer properties. The aim of this study was to investigate the protective efficacy of chrysin against cisplatin-induced nephrotoxicity.. Thirty male Wistar rats were divided into five groups with six rats in each group. Group I served as control and received corn oil (vehicle of chrysin) for 14 days and 0.9% saline (vehicle of cisplatin) on day 14 only. Group II received a single intraperitoneal injection of cisplatin on day 14. Group III and IV were pretreated with two different doses of chrysin in addition to cisplatin and group V received chrysin only. Rats were examined for the effect of chrysin on cisplatin induced depletion of antioxidant enzymes, induction of lipid peroxidation and DNA damage in the kidney, utilizing a well-established model of cisplatin-induced nephropathy.. Pretreatment with chrysin significantly attenuated cisplatin-induced renal oxidative damage by diminishing the DNA damage and toxicity markers, such as creatinine and blood urea nitrogen, lipid peroxidation and xanthine oxidase activity, accompanied by increase in enzymatic (catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase) and non-enzymatic (reduced glutathione) antioxidant status. Histological findings further substantiated the protective efficacy of chrysin, which reduced cisplatin-induced renal damage.. The data of the present study suggest that chrysin effectively suppress cisplatin-induced renal injury by ameliorating oxidative stress.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Biomarkers; Blood Urea Nitrogen; Cisplatin; Creatinine; DNA Damage; Flavonoids; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Neoplasms; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Renal Agents; Xanthine Oxidase

Topics: Adrenal Cortex Hormones; Adult; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Diseases; Male

Uric acid nephropathy (UAN) is due to excessive uric acid, which leads to hyperuricemia and kidney damage via the deposition of urate microcrystals in the kidneys. Iridoid glycosides of Paederia scandens (IGPS) is a major active component isolated from the traditional Chinese herb P. scandens (LOUR.) MERRILL (Rubiaceae). This study aimed to evaluate the anti-inflammatory and immunomodulatory effects of IGPS and its mechanism on UAN rats.. The experimental model of UAN rats was induced by using uricopoiesis promoter adenine and uricase inhibitor potassium oxonate (PO). Treatment groups received three different doses of IGPS, allopurinol (AP) and benzbromarone (BEN) daily for 24days respectively. The histopathology of renal tissues in UAN rats were assessed for conventional morphological evaluation. The nuclear factor-κBp65 (NF-κBp65), monocyte chemoattractant protein-1 (MCP-1) and α-smooth muscle actin (α-SMA) protein expression of renal tissues in UAN rats were investigated by immunohistochemistry. MCP-1 and α-SMA mRNA levels were monitored by method of reverse transcription polymerase chain reaction (RT-PCR).. Treatment with IGPS significantly ameliorated UAN induced renal tissue injury, inhibited the biological activity of NF-κBp65, MCP-1 and α-SMA, and suppressed the mRNA expressions of MCP-1 and α-SMA.. IGPS exerts a protective effect against renal injury in UAN rats, possesses anti-inflammatory and immunomodulatory effects by inactivating NF-κBp65 pathway transmembrane signal transduction, down regulating the expression of MCP-1 and α-SMA to modulate pro-inflammatory mediator production in nephropathy tissue to improve renal fibrosis in UAN rats.

Topics: Actins; Allopurinol; Animals; Anti-Inflammatory Agents; Benzbromarone; Chemokine CCL2; Cyclopentane Monoterpenes; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Glucosides; Immunologic Factors; Iridoid Glycosides; Kidney; Kidney Diseases; Male; Medicine, Chinese Traditional; Pyrans; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Rubiaceae; Transcription Factor RelA; Uric Acid

This study was designed to investigate the possible effect of sitagliptin on renal damage induced by renal ischemia reperfusion (I/R) in diabetic rats. T2DM in rats was induced by the administration of nicotinamide (230 mg/kg, i.p.), 15 min prior to a single dose of streptozotocin (65 mg/kg, i.v.). In vivo renal I/R was performed in both T2DM and normal rats. Each protocol comprised ischemia for 30 min followed by reperfusion for 24h and a treatment period of 14 days before induction of ischemia. Sitagliptin treated diabetic rats that underwent renal I/R demonstrated significant decrease in the serum concentrations of aspartate aminotransferase (p < 0.01), urea nitrogen (p < 0.01) and creatinine (p < 0.001) compared to renal I/R in diabetic rats. Lipid peroxidation, xanthine oxidase activity, myeloperoxidase activity and nitric oxide level in renal tissue were significantly (p < 0.05, p < 0.001, p < 0.01, p < 0.05 respectively) decreased after renal I/R in sitagliptin treated rats compared to diabetic rats. Antioxidant enzymes like glutathione (p < 0.05), glutathione peroxidase (p < 0.001), superoxide dismutase (p < 0.05) and catalase (p < 0.001) were significantly increased after renal I/R in sitagliptin treated diabetic rats compared to non treated diabetic rats. The typical DNA laddering was observed when renal I/R performed in diabetic rats, which indicates cell apoptosis. Sitagliptin treated rats demonstrated a decrease in DNA fragmentation and apoptosis. Furthermore, renal histopathology preserved in sitagliptin treated rats verified protection against renal I/R in diabetes. The results of present investigation established sitagliptin treatment attenuated renal damage induced by renal I/R in diabetic rats.

Topics: Animals; Apoptosis; Catalase; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; DNA Fragmentation; Female; Glutathione; Glutathione Peroxidase; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Oxidative Stress; Peroxidase; Pyrazines; Rats; Rats, Wistar; Reperfusion Injury; Sitagliptin Phosphate; Superoxide Dismutase; Triazoles; Xanthine Oxidase

To determine if the association between hyperuricaemia and poor outcomes in heart failure (HF) varies by chronic kidney disease (CKD).. Of the 2645 systolic HF patients in the Beta-Blocker Evaluation of Survival Trial with data on baseline serum uric acid, 1422 had hyperuricaemia (uric acid ≥6 mg/dL for women and ≥8 mg/dL for men). Propensity scores for hyperuricaemia, estimated for each patient, were used to assemble a matched cohort of 630 pairs of patients with and without hyperuricaemia who were balanced on 75 baseline characteristics. Associations of hyperuricaemia with outcomes during 25 months of median follow-up were examined in all patients and in those with and without CKD (estimated glomerular filtration rate of <60 mL/min/1.73 m(2)). Hyperuricaemia-associated hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality and HF hospitalization were 1.44 (1.12-1.85, P = 0.005) and 1.27 (1.02-1.58, P = 0.031), respectively. Hazard ratios (95% CIs) for all-cause mortality among those with and without CKD were 0.96 (0.70-1.31, P = 0.792) and 1.40 (1.08-1.82, P = 0.011), respectively (P for interaction, 0.071), and those for HF hospitalization among those with and without CKD were 0.99 (0.74-1.33, P = 0.942) and 1.49 (1.19-1.86, P = 0.001), respectively (P for interaction, 0.033).. Hyperuricaemia has a significant association with poor outcomes in HF patients without CKD but not in those with CKD, suggesting that hyperuricaemia may predict poor outcomes when it is primarily a marker of increased xanthine oxidase activity, but not when it is primarily due to impaired renal excretion of uric acid.

Topics: Aged; Canada; Chronic Disease; Female; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Hyperuricemia; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Multicenter Studies as Topic; Prognosis; Propensity Score; Randomized Controlled Trials as Topic; United States; Xanthine Oxidase

Although there have been many studies on this topic, the molecular mechanism of the toxic effects of hyperammonemia on cells has not yet been fully explained. Recent studies have held oxidative stress mechanisms responsible for hyperammonemia-induced cell damage. Kidney functions are affected in diseases associated with an increase in ammonia in the blood. Our study tries to determine whether oxidative stress mechanisms are responsible for kidney damage in chronic hyperammonemia. We also investigated whether kidney damage is dependent on possible reactive oxygen products associated with the xanthine oxidase (XO) enzyme and whether the possible association can be inhibited with allopurinol, an XO enzyme inhibitor. The study took into consideration the enzyme activities of XO, xanthine dehydrogenase (XDH), superoxide dismutase (SOD), glutathione-S-transferase (GST), as well as protein thiol (P-SH) and malondialdehyde (MDA) levels. The data found demonstrated that chronic hyperammonemia had oxidative stress effects on the kidney, and that kidney XO and XDH activity changed. However, it was not possible to inhibit this oxidative stress in the kidney using allopurinol. Thus, we could not conclude that oxidative stress is an XO-dependent mechanism. The outcomes of the study suggested that this oxidative situation arising in hyperammonemia occurred through a mechanism other than the XO enzyme.

Topics: Allopurinol; Animals; Chronic Disease; Female; Free Radical Scavengers; Hyperammonemia; Kidney Diseases; Oxidative Stress; Rats; Rats, Wistar; Xanthine Oxidase

Topics: Aged; Allopurinol; Australia; Colchicine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Febuxostat; Glomerular Filtration Rate; Gout; Gout Suppressants; Humans; Kidney Diseases; Male; Patient Compliance; Practice Guidelines as Topic; Prednisolone; Renal Dialysis; Thiazoles; Uric Acid

To study the preventive and therapeutic effects of Quercetin (Que) on hyperuricemia and renal failure in rats.. Seventy rats were divided into ten groups, normal control group, model control group, allopurinol group and seven Que groups (50, 40, 30, 20, 10, 5 and 2.5 mg/kg). Hyperuricemia and renal failure in rats were induced by adenine and ethambutol hydrochloride intragastrically, and then Que was given for 3 weeks. The items related to high serum uric acid and renal injury were observed.. Levels of serum uric acid (SUA), serum urea nitrogen ( SUN), serum creatinine (SCr), malonaldehyde (MDA) and the activity of xanthine oxidase (XOD) in liver were lowered effectively by Que, and the activity of superoxide dismutase (SOD) in serum was increased. The better results of lowering serum uric acid and protecting against renal failure were at the dosage of Que between 10 and 20 mg/kg.. Hyperuricemia and renal failure in rats could be intervened by Que. The possible mechanism might be inhibiting the activity of liver XOD and improving the ability of clearing oxygen free radicals and reducing lipid peroxidation, which might play an important role in reducing serum uric acid level and protecting kidney.

Topics: Adenine; Animals; Antioxidants; Blood Urea Nitrogen; Creatinine; Ethambutol; Hyperuricemia; Kidney Diseases; Male; Protective Agents; Quercetin; Rats; Rats, Sprague-Dawley; Xanthine Oxidase

Astilbin is a flavonoid compound isolated from the rhizome of Smilax china L. The effects and possible mechanisms of astilbin on hyperuricemia and nephropathy rats were elucidated in this study. Different dosages of astilbin (1.25, 2.5, and 5.0 mg/kg) were administered to 10 % fructose-induced hyperuricemic rats. The results demonstrated that astilbin significantly decreased the serum uric acid (Sur) level by increasing the urinary uric acid (Uur) level and fractional excretion of urate (FEUA) but not inhibiting the xanthine oxidase (XOD) activity. In addition, kidney function parameters such as serum creatinine (Scr) and blood urea nitrogen (BUN) were recovered in astilbin-treated hyperuricemic rats. Further investigation indicated that astilbin prevented the renal damage against the expression of transforming growth factor- β1 (TGF-β1) and connective tissue growth factor (CTGF) and also exerted a renal protective role by inhibiting formation of monosodium urate (MSU) and production of prostaglandin E₂ (PGE₂) and interleukin-1 (IL-1). These findings provide potent evidence for astilbin as a safe and promising lead compound in the development of a disease-modifying drug to prevent hyperuricemia and nephropathy.

Topics: Animals; Blood Urea Nitrogen; Connective Tissue Growth Factor; Creatinine; Dinoprostone; Disease Models, Animal; Drugs, Chinese Herbal; Flavonols; Fructose; Hyperuricemia; Interleukin-1; Kidney; Kidney Diseases; Male; Phytotherapy; Rats; Rats, Sprague-Dawley; Rhizome; Smilax; Transforming Growth Factor beta1; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Drug Costs; Humans; Hypoxanthine; Kidney Diseases; Tumor Lysis Syndrome; Urate Oxidase; Xanthine

Ischemia and subsequent reperfusion (IR) may induce local and remote organ reperfusion injury. It may be propagated by xanthine oxidase (XO)-generated oxidant stress. We investigated whether pancreas IR directly and acutely induces renal dysfunction and if this outcome could be prevented by mannitol.. Rat pancreases were isolated and perfused with Krebs-Henseleit solution enriched with 5% bovine albumin. Other rats donated kidneys that were perfused at constant pressure mode. Each pancreas underwent 45 min of either perfusion (control) or ischemia (no flow). Both organ perfusion systems were then combined and the kidneys were perfused with the pancreatic 15-min reperfusate for 2 h. A third group consisted of paired ischemic pancreases and nonischemic kidneys treated with mannitol 250 mg/kg body weight during reperfusion.. The controls demonstrated no abnormal perfusion or metabolite changes. Pancreas and renal perfusion pressures increased by >50% in the ischemia group immediately upon reperfusion; it remained above the values of controls during the 2-h kidney reperfusion. Conversely, perfusion pressure in the treatment group was not significantly different from the control. The reduced glutathione level increased significantly, as did XO, immediately upon starting reperfusion in both organs appertaining to the ischemic group; this misbalance was not documented in the controls and the mannitol-treated groups. Urine output was severely reduced in the IR kidneys.. Ischemia/reperfusion of the rat pancreas evokes immediate renal dysfunction. Kidney oxidant-antioxidant balance is disturbed, but can be prevented with mannitol. These two figures underline the role of oxidative stress in promoting acute renal damage in the presence of pancreas IR.

Topics: Animals; Diuretics, Osmotic; In Vitro Techniques; Kidney; Kidney Diseases; Male; Mannitol; Oxidative Stress; Pancreas; Pancreas Transplantation; Pancreatitis; Perfusion; Rats; Rats, Wistar; Reperfusion Injury; Xanthine Oxidase

2,8-dihydroxyadeninuria (DHA) disease (also called 2,8 dihydroxyadeninuria) is a rare autosomal recessive disorder caused by complete adenine phosphoribosyltransferase deficiency and typically manifests as recurrent nephrolithiasis. Only rare cases of DHA nephrolithiasis have been reported from the USA. Herein, we report three American patients who developed DHA crystalline nephropathy leading to end-stage renal disease (ESRD) with recurrence in the allograft.. Three cases of DHA crystalline nephropathy were identified from the Renal Pathology Laboratory of Mayo Clinic. Detailed clinical and pathologic descriptions are provided.. All three patients were Caucasian adults with no history of obstructive nephropathy. Two patients had no history of nephrolithiasis and one had a single episode of stones 36 years prior to presentation. All patients presented with severe renal failure with a mean serum creatinine of 7.5 mg/dl. Renal biopsies revealed numerous tubular and interstitial brown DHA crystals, tubular degenerative changes and moderate to marked tubulointerstitial scarring. Two patients were initially misdiagnosed, one as primary hyperoxaluria and the other as chronic interstitial nephritis. All three patients progressed to ESRD, within 1 month following renal biopsy in two and after 9 months in one. All three patients underwent renal transplantation with early disease recurrence in three allografts in two patients.. DHA disease is an under-recognized condition that can lead to irreversible renal failure and frequently recurs in the transplant. It should be included in the differential diagnosis of crystalline nephropathy, even in the absence of history of nephrolithiasis.

Topics: Adenine; Adenine Phosphoribosyltransferase; Adult; Allopurinol; Crystallization; Diagnosis, Differential; Female; Genes, Recessive; Humans; Hyperoxaluria, Primary; Kidney; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Recurrence; United States; Urinary Calculi

Carbon tetrachloride exerts its toxicity in rat kidneys through oxidative stress. Launaea procumbens is used ethnopharmacologically in renal disorders. Its methanolic, chloroform, ethyl acetate, and n-hexane fractions were evaluated against CCl(4)-induced nephrotoxicity in rat.. Among 16 groups, one was given CCl(4) of 3ml/kg body weight (30% in olive oil i.p.) twice a week for 4 weeks. Others were orally fed with extracts (100, 200mg/kg b.w.) or rutin (50mg/kg b.w.) after 48h of CCl(4) or 200mg/kg b.w. of extracts without CCl(4)-treatment twice a week for 4 weeks.. CCl(4) exposure led to a significant oxidative stress in kidneys which was remarkably attenuated with co-administration of various fractions and rutin thereby increased the level of CAT, POD, SOD, GSH, GSR, GST, GSH-Px, quinone reductase, while reduced the xanthine oxidase, gamma-GT, TBARS, H(2)O(2), nitrite, tissue proteins and DNA fragmentation%. Ameliorated effects of fractions and rutin were also recorded for the function of kidneys and the level of urobilinogen, urea, albumin, creatinine, RBC and WBC in urine were decreased. Serum level of creatinine, urobilinogen, BUN, direct bilirubin, total bilirubin and globulin were decreased while total proteins, albumin and creatinine clearance were increased with fractions and rutin. Protective effects of rutin and fractions were also evident on histopathology by reducing glomerular atrophy, tubular degeneration, congestion of blood capillaries, necrosis of epithelium and edema. Similarly body weight was increased while kidney and relative kidney weight was decreased with co-administration of fractions and rutin.. It is suggested that Launaea procumbens effectively protect kidneys against the CCl(4)-induced oxidative damage in rats, through antioxidant and free radical scavenging effects of flavonoids and saponins present in the fractions.

Topics: Animals; Antioxidants; Asteraceae; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Creatinine; Glutathione; Hexanes; Hydrogen Peroxide; Kidney; Kidney Diseases; Male; Nitrites; Oxidative Stress; Rats; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Xanthine Oxidase

Topics: Allopurinol; Angina Pectoris; Glomerular Filtration Rate; Humans; Kidney Diseases

Physiologic renal changes associated with pneumoperitoneum (PNP) have been described and various underlying mechanisms have been suggested. We investigated the possibility that PNP-associated renal damage is pressure dependent, and that oxidative stress is thereby involved.. Seventy Wistar rat kidneys (n=10 per group) were isolated. They were perfused with oxygenated, warm, Krebs-Henseleit solution containing 5% albumin within an isolated environment and subjected to various CO(2) pressures (0 [control], 3, 5, 8, 12, 15, and 18 mmHg) for 60 min. Half of each group was additionally perfused for 30 min at 0 mmHg pressure.. Renal flow decreased proportionately to the applied pressure as did urine output: both decreased (P < 0.05) after 60 and 90 min when pressure >or=8 mmHg was applied. Oxygen extraction decreased (P<0.05) during PNP in all pressurized groups. Xanthine oxidase (XO) activity and reduced glutathione in the tissues increased (P<0.05) proportionately to pressures >or=8 mmHg. All parameters slightly reversed toward baseline values, upon the release of the intra-chamber pressure, except for the 18 mmHg group's values.. CO(2)-PNP pressure induces kidney injury, possibly reversible immediately after pressure is annulled. Pressure is associated with oxidative stress, which interferes with cellular metabolism and function, possibly via an ischemic-reperfusion-like mechanism.

Topics: Animals; Carbon Dioxide; Disease Models, Animal; Glutathione; Kidney; Kidney Diseases; Male; Oxidative Stress; Oxygen; Pneumoperitoneum, Artificial; Rats; Rats, Wistar; Renal Circulation; Urodynamics; Xanthine Oxidase

Topics: Allopurinol; Antimetabolites; Biomarkers; Cardiovascular Diseases; Humans; Hyperuricemia; Kidney Diseases; Risk Factors; Uric Acid

This study aimed to elucidate the role of L-type fatty acid-binding protein (L-FABP) in renal tubulointerstitial injury using a mouse adenine-induced renal injury model. C57BL/6 mice fed excess dietary adenine for 6 weeks showed a gradual increase in levels of blood urea nitrogen (BUN). They also showed severe tubulointerstitial pathological findings, such as fibrosis and macrophage infiltration without glomerular damage, which were attenuated by treatment with either allopurinol or Y-700, a new xanthine dehydroxygenase inhibitor. Because renal expression of L-FABP is defective in C57BL/6 mice, human L-FABP transgenic mice were fed an adenine-containing diet. Transgenic mice showed lower BUN levels and lower levels of pathological injury compared with wild-type mice. On the other hand, urinary levels and renal expression of L-FABP in the adenine group was significantly increased and attenuated by treatment with either allopurinol or Y-700. Urinary L-FABP was positively correlated with BUN levels and pathological damages in the tubulointerstitium. No increases in urinary protein, albumin, or N-acetyl-beta-D-glucosaminidase levels were found for 6 weeks in any group. In conclusion, we demonstrated that urinary L-FABP levels can be used to monitor both dynamics and drug responses in a mouse adenine-induced tubulointerstitial injury model.

Topics: Allopurinol; Animals; Biomarkers; Blood Urea Nitrogen; Blotting, Western; Chemokine CCL2; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Fatty Acid-Binding Proteins; Humans; Kidney Diseases; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pyrazoles; Reverse Transcriptase Polymerase Chain Reaction; Transforming Growth Factor beta1

The aim of this study was to examine the prophylactic protective effects of 3,4-methylenedioxyphenol (sesamol) on ferric-nitrilotriacetate (Fe-NTA)-induced acute renal damage in mice. We induced acute renal injury in mice by treating them with 4 mg/kg of Fe-NTA for 3h. We used blood biochemistry, creatinine clearance, and histological examinations to assess renal function. With a high-performance chemiluminescence analyzer, we also determined the hydroxyl radical and superoxide anion levels (free radicals) generated. Renal xanthine oxidase activities were also assessed. Sesamol inhibited Fe-NTA-induced acute renal injury, renal lipid peroxidation, the levels of renal hydroxyl radical and superoxide anion generated, and the activity of xanthine oxidase in mice. Therefore, we concluded that sesamol protected mice against Fe-NTA-induced oxidative-stress-associated acute renal injury by at least partially inhibiting the production of reactive oxygen species.

Topics: Animals; Antioxidants; Benzodioxoles; Blood Urea Nitrogen; Chelating Agents; Creatinine; Dose-Response Relationship, Drug; Ferric Compounds; Hydroxyl Radical; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Mice; Mice, Inbred BALB C; Nitrilotriacetic Acid; Oxidants; Phenols; Protective Agents; Proteins; Superoxides; Xanthine Oxidase

A study was conducted to determine whether combination treatment using allopurinol and benzbromarone was more useful than single allopurinol treatment for the gout and hyperuricemia accompanying renal dysfunction. The subjects were 45 male patients who received urate-lowering treatment and showed a stable serum urate level. The patients were divided into four groups according to the urate-lowering treatment and creatinine clearance (Ccr) (A group: single treatment, normofunction, B group: single treatment, hypofunction, C group: combined treatment, normofunction, D group: combined treatment, hypofunction). There were no differences in serum urate levels among the four groups. Urate clearance (CUA)and daily urinary urate excretion (UUAV) showed significantly high values in the C group, but no difference was seen in the fractional excretion of urate (FEUA) among the four groups. The dosage of allopurinol in the D group was significantly lower than in the A and B groups. Serum oxypurinol concentration in the C group was lower than that in the B group. Oxypurinol clearance (C oxypurinol) in the C group was significantly high compared with the B and D groups. There was a close correlation between C oxypurinol, Ccr, and CUA, with an especially strong correlation between C oxypurinol and CUA. There were no differences in the serum concentration and clearance of xanthine and hypoxanthine among the four groups. Results of the study suggested that combination treatment using allopurinol and benzbromarone for the gout and hyperuricemia accompanying renal dysfunction is more useful, because a lower dose of allopurinol can be used and the serum oxypurinol concentration is reduced compared with single allopurinol treatment.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Benzbromarone; Drug Therapy, Combination; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Diseases; Male; Middle Aged; Oxypurinol; Retrospective Studies

The goal of this study was to test the hypothesis that NADPH oxidase contributes importantly to renal cortical oxidative stress and inflammation, as well as renal damage and dysfunction, and increases in arterial pressure. Fifty-four 7- to 8-wk-old Dahl salt-sensitive (S) or R/Rapp strain rats were maintained for 5 wk on a high sodium (8%) or high sodium + apocynin (1.5 mmol/l in drinking water). Arterial and venous catheters were implanted on day 21. By day 35 in the high-Na S rats, mRNA expression of renal cortical gp91phox, p22phox, p47phox, and p67phox NADPH subunits in S rats increased markedly, and treatment of high-Na S rats with the NADPH oxidase inhibitor apocynin resulted in significant decreases in mRNA expression of these NADPH oxidase subunits. At the same time, in apocynin-treated S rats 1) renal cortical GSH/GSSG ratio increased, 2) renal cortical O2(.-) release and NADPH oxidase activity decreased, and 3) renal glomerular and interstitial damage markedly fell. Apocynin also decreased renal cortical monocyte/macrophage infiltration, and apocynin, but not the xanthine oxidase inhibitor allopurinol, attenuated decreases in renal hemodynamics and lowered arterial pressure. These data suggest that NADPH oxidase plays an important role in causing renal cortical oxidative stress and inflammation, which lead to decreases in renal hemodynamics, renal cortical damage, and increases in arterial pressure.

Topics: Acetophenones; Allopurinol; Animals; Blood Pressure; Disease Models, Animal; Enzyme Inhibitors; Gene Expression Regulation, Enzymologic; Glomerular Filtration Rate; Glutathione; Glutathione Disulfide; Heart Rate; Hemodynamics; Hypertension; Inflammation; Kidney Cortex; Kidney Diseases; Macrophages; Monocytes; NADPH Oxidases; Oxidative Stress; Protein Subunits; Proteinuria; Rats; Rats, Inbred Dahl; Renal Circulation; RNA, Messenger; Sodium Chloride, Dietary; Superoxides; Time Factors; Xanthine Oxidase

It has been demonstrated that hyperuricemia induces reno-cardiovascular damage resulting in hypertension and renal injury because of vascular endothelial dysfunction. The pathogenesis of hyperuricemia, endothelial dysfunction, hypertension, and renal injury is progressive, and develops into a vicious cycle. It is reasonable to suggest that an antihypertensive drug with endothelial protection may block this vicious cycle. Iptakalim, a novel antihypertensive drug undergoing phase-three clinical trials, is a new ATP-sensitive potassium channel opener and can ameliorate endothelial dysfunction. We hypothesized that iptakalim could prevent hypertension and retard the pathogenesis of endothelial dysfunction and renal injury in hyperuricemic rats.. In rats with hyperuricemia induced by 2% oxonic acid and 0.1 mmol/l uric acid, iptakalim prevented increases in systolic blood pressure, reduced the impairment of endothelial vasodilator function, and attenuated renal dysfunction and pathological changes in glomerular and renal interstitial tissue at 0.5, 1.5, and 4.5 mg/kg orally daily for 4 weeks. Serum levels of nitric oxide and prostacyclin, and gene expression of endothelial nitric oxide synthase in the aortic and intrarenal tissue, were increased, whereas the serum levels of endothelin-1 and gene expression of endothelin-1 in aortic and intrarenal tissue were decreased. However, serum levels of angiotensin II and renin remained unchanged in the hyperuricemic rats treated with iptakalim. In cultured rat aortic endothelial cells, amelioration of endothelial dysfunction by iptakalim was suggested by inhibition of the overexpression of intercellular adhesive molecule-1, vascular cell adhesive molecule-1, and monocyte chemoattractant protein-1 mRNA induced by uric acid, and reversal of the inhibitory effects of uric acid on nitric oxide release in a concentration-dependent manner, which could be abolished by pretreatment with glibenclamide, an ATP-sensitive potassium channel blocker. Iptakalim ameliorated hyperuricemia in this rat model by decreasing renal damage through its antihypertensive and endothelial protective properties, and it had no direct effects on anabolism, catabolism and excretion of uric acid.. These findings suggest that the activation of ATP-sensitive potassium channels by iptakalim can protect endothelial function against hypertension and renal injury induced by hyperuricemia. Iptakalim is suitable for use in hypertensive individuals with hyperuricemia.

Topics: 6-Ketoprostaglandin F1 alpha; Angiotensin II; Angiotensins; Animals; Cells, Cultured; Disease Models, Animal; Endothelin-1; Endothelium, Vascular; Hypertension; Hyperuricemia; KATP Channels; Kidney; Kidney Diseases; Male; Nitric Oxide; Oxonic Acid; Propylamines; Rats; Rats, Sprague-Dawley; Urate Oxidase; Uric Acid; Xanthine Oxidase

Potassium bromate (KBrO3) is an oxidizing agent used as a food additive which causes kidney damage as a potent nephrotoxic agent, and the mechanism may be explained by the generation of oxygen free radicals. Our experiments showed that single intraperitoneal administration of 200 mg/kg KBrO3 could induce serious kidney damage, with an increase in serum blood urea nitrogen (BUN) and creatinine levels. Five-day oral administration of bilberry ( Vaccinium myrtillus L.) extract at 50, 100, and 200 mg/kg resulted in a reversal in serum BUN and creatinine to normal levels and decreased kidney malondialdehyde (MDA), nitric oxide (NO), and xanthine oxidase (XOD) levels. Also, bilberry extract improved oxygen radical absorbance capacity (ORAC) levels in kidney tissue, which showed that bilberry extract reduced the degree of oxidative stress and kidney damage induced by KBrO3. These findings demonstrate that the protective effect of bilberry extract is attributed to its free radical scavenging activity and lipid peroxidation inhibitory effect.

Topics: Animals; Anthocyanins; Antioxidants; Blood Urea Nitrogen; Bromates; Kidney; Kidney Diseases; Male; Malondialdehyde; Mice; Nitric Oxide; Plant Extracts; Vaccinium myrtillus; Xanthine Oxidase

Topics: Allopurinol; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Kidney Diseases; Oxidative Stress; Oxypurinol; Uric Acid

To assess concordance of the management of chronic gout in UK primary care with the European League Against Rheumatism (EULAR) gout recommendations.. A postal questionnaire was sent to all adults aged >30 years registered with two general practices. Patients with possible gout attended for clinical assessment, at which the diagnosis was verified clinically. Aspects of chronic gout management, including provision of lifestyle modification advice, use of urate-lowering therapies (ULT) including dose titration to serum urate (SUA) level, prophylaxis against acute attacks, and diuretic cessation were assessed in accordance with the EULAR recommendations.. Of 4249 (32%) completed questionnaires returned, 488 reported gout or acute attacks and were invited for clinical assessment. Of 359 attendees, 164 clinically confirmed cases of gout were identified. Advice regarding alcohol consumption was recalled by 59 (41%), weight loss by 36 (25%) and diet by 42 (29%). Allopurinol was the only ULT used and was taken by 44 (30%); 31 (70%) were taking 300 mg daily. Mean SUA was lower in allopurinol users than non-users (318 vs 434 micromol/l) and was less often >360 micromol/l in allopurinol users (23% vs 75%). Eight patients had recently commenced allopurinol; two of these also were taking prophylactic colchicine or non-steroidal anti-inflammatory drugs. Of 25 patients with diuretic-induced gout, 16 (64%) were still taking a diuretic.. Treatment of chronic gout is often suboptimal and poorly concordant with EULAR recommendations. Lifestyle advice is infrequently offered, and allopurinol is restricted to a minority. Persistent hyperuricaemia was often seen in allopurinol non-users, but was also in allopurinol users, suggesting that doses >300 mg are often necessary.

Topics: Adult; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Colchicine; Diuretics; England; Family Practice; Female; Gout; Gout Suppressants; Humans; Kidney Diseases; Male; Middle Aged; Practice Guidelines as Topic; Uric Acid; Uricosuric Agents

In an effort to identify a new chemopreventive agent, the present study was conducted to investigate the role of T. chebula in the prevention of ferric nitrilotriacetic acid (Fe- NTA) induced oxidative stress and renal tumorigenesis in Wistar rats. A single application of Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) significantly induced oxidative stress and elevated the marker parameters of tumor promotion. However, the pretreatment of animals with different doses of T. chebula extract (25 and 50 mg/kg body weight) restored the levels of reduced glutathione (GSH) and cellular protective enzymes (p < 0.05). Concomitantly, malondialdehyde (MDA) formation and hydrogen peroxide content were also reduced significantly (p < 0.05) at both the doses. The promotion parameters tested (ornithine decarboxylase activity and DNA synthesis) were also significantly suppressed (p < 0.05). T. chebula also inhibited N-diethyl nitrosamine initiated renal carcinogenesis by showing reduction in the number of animals with renal cell tumors and percentage incidence of tumor as compared to the DEN initiated and Fe-NTA promoted rats. The study was further histologically confirmed. These results suggest a potential role of T. chebula in protection from Fe-NTA-induced renal carcinogenesis and oxidative damage.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Carcinogens; Cell Proliferation; Chelating Agents; DNA; Ferric Compounds; Glutathione; Kidney; Kidney Diseases; Kidney Function Tests; Kidney Neoplasms; Lipid Peroxidation; Male; Microsomes; Nitrilotriacetic Acid; Oxidative Stress; Plant Extracts; Quinone Reductases; Rats; Rats, Wistar; Terminalia; Xanthine Oxidase

Inappropriate use of drugs in patients with renal impairment (RI) may be harmful and may have deleterious effects. We aimed to investigate the use of renal risk drugs in such patients in general hospitals and to analyse the relationship to demographic factors, risk factors and occurrence of drug-related problems (DRPs).. Patients admitted to departments of internal medicine and rheumatology in five general hospitals were included. We recorded demographic data, drugs used, drugs described to be a risk in RI (renal risk drugs), relevant medical history, laboratory data and clinical/pharmacological risk factors. We used levels of glomerular filtration rates, calculated by the Modification of Diet in Renal Disease formula to classify patients into five stages of renal function. DRPs were recorded and assessed in multidisciplinary hospital team discussions.. Of the 808 included patients, 293 (36%) had normal renal function (stage 1), 314 (39%) had mild RI (stage 2), 160 (20%) had moderate RI (stage 3), 35 (4%) had severe RI (stage 4) and six (0.7%) had kidney failure (stage 5). Mean number of drugs used per patient in patients with RI (stages 3, 4 and 5) and patients evaluated to have adequate renal function relative to drug therapy (stages 1 and 2): on admission 6.2 vs 4.1; started in hospital 4.3 vs 3.9 and total number of renal risk drugs 6.1 vs 4.5. All but six patients with RI stages 3, 4 and 5 used two or more renal risk drugs. 124 (62%) of the patients with RI stages 3, 4 and 5 had DRPs linked to the renal risk drugs, and 26% of the renal risk drugs were associated with DRPs. The most common drug classes associated with DRPs were antibacterials, antithrombotic agents, angiotensin-converting enzyme (ACE) inhibitors, opioids and non-steroidal anti-inflammatory drugs (NSAIDs).. Among patients admitted to general hospitals, a considerable proportion had renal impairment. In patients with reduced renal function, renal risk drugs were widely used and often in combination. DRPs were frequently associated with the use of renal risk drugs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Female; Fibrinolytic Agents; Glomerular Filtration Rate; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Patient Admission; Pharmaceutical Preparations; Prospective Studies; Risk Factors

Renal disease is rare today in classic adult gout, and gout is rare in renal disease--especially in the young. Here we summarise studies in 158 patients from 31 kindreds diagnosed with familial juvenile hyperuricaemic nephropathy FJHN from a total of 230 kindred members studied in Great Britain. Some patients have been followed for up to 30 years, and allopurinol has ameliorated the progression of the renal disease in all 113 surviving members provided: They have been diagnosed and treated sufficiently early. Compliance with allopurinol treatment and diet has been as important as early recognition. Hypertension has been rigorously controlled. The use of oral contraceptives has been avoided, as has pregnancy in any female with a Glomelar Filtration Rate GFR <70 ml/min. The question arising is: Why is FJHN the most prevalent genetic purine disorder diagnosed in Britain? Is it a lack of awareness which needs to be improved Europe-wide?

Topics: Adolescent; Adult; Allopurinol; Child; Disease Progression; Family Health; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Nephritis, Hereditary; Pedigree; Purine-Pyrimidine Metabolism, Inborn Errors; Time Factors; United Kingdom

To determine a rat strain appropriate for carcinogenicity testing of FYX-051, a xanthine oxidoreductase inhibitor, we performed a 4-week oral toxicity study by administering 0.3, 1 and 3 mg/kg, and 1, 3 and 10 mg/kg of FYX-051 to male Sprague-Dawley (SD) and Fischer (F344) rats, respectively. Histopathology revealed that the degree of FYX-051-induced nephropathy was 3-fold stronger in SD rats than in F344 rats. Our previous study demonstrated that the key factor of species differences in FYX-051-induced nephropathy is purine metabolism. This observation led us to examine the involvement of purine metabolism in differences among two strains of rats. However, purine metabolism was proven not to be implicated as an important factor. Subsequently, other factors responsible for the strain differences were examined. FYX-051-induced increases in plasma xanthine concentrations were higher in SD rats than in F344 rats, suggesting more remarkable effects on pharmacodynamics in the former than the latter. Urinary volume was greater in F344 rats administered 10 mg/kg of FYX-051 (6.8 ml/h/kg) than in SD rats administered 3 mg/kg of FYX-051 (5.0 ml/h/kg), implying easier xanthine excretion in the former. Urinary xanthine solubility was 55 mg/dl in F344 rats aged 6 weeks, in contrast to 38 mg/dl in SD rats of the same age. Also, there were no significant differences in exposure levels at the same dose between SD and F344 rats. The outcomes of exposure levels and renal histopathology in both rats suggest the possibility that F344 rats could be exposed to a 3-fold higher amount of drug than SD rats in a carcinogenicity bioassay. The present study, therefore, suggested that strain differences of nephrotoxicity were caused by the combined effects of pharmacodynamics, xanthine excretion capacity, and urinary xanthine solubility. Furthermore, these results indicate that F344 rats would be a suitable strain for the carcinogenicity study of FYX-051.

Topics: Animals; Area Under Curve; Dose-Response Relationship, Drug; Enzyme Inhibitors; Kidney; Kidney Diseases; Nitriles; Organ Size; Pyridines; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Species Specificity; Toxicity Tests; Xanthine Oxidase

The possible mechanism of the underlying nephropathy found in the rat toxicity study of FYX-051, a xanthine oxidoreductase inhibitor, was investigated. Rats received oral treatment of either 1 or 3 mg/kg of FYX-051, with and without citrate for four weeks to elucidate whether nephropathy could be caused by materials deposited in the kidney. Furthermore, analysis of the renal deposits in rats was also performed. Consequently, interstitial nephritis comprising interstitial inflammatory cell infiltration, dilatation, basophilia and epithelial necrosis of renal tubules and collecting ducts, deposits in renal tubules and collecting ducts, and so forth was seen in six of the eight rats and in all eight rats in the 1 and 3 mg/kg FYX-051 alone groups, respectively, with the intensity in the 3 mg/kg group being moderate to severe. In the simultaneous treatment with citrate group, however, no alterations were observed in the kidney, except for minimal interstitial nephritis in one instance in the 3 mg/kg FYX-051 + citrate group along with an increased urinary pH, leading to an increase in xanthine solubility. Analysis of intrarenal deposits showed that the entity would be composed of xanthine crystals. The present study, therefore, showed that nephropathy in rats occurring after the administration of FYX-051 was a secondary change caused by xanthine crystals being deposited in the kidney, and no other causes could be implicated in this kidney lesion.

Topics: Animals; Citric Acid; Crystallization; Dogs; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Kidney Diseases; Macaca fascicularis; Male; Nitriles; Pyridines; Rats; Rats, Sprague-Dawley; Xanthine; Xanthine Dehydrogenase; Xanthine Oxidase

To investigate if increased lipid peroxidation is involved in hypercholesterolemia-induced hypertension and renal injury, we examined the effects of allopurinol, a xanthine oxidase inhibitor, on these conditions. Groups of male Sprague--Dawley rats were fed for 8 weeks with a high-cholesterol diet (4% cholesterol), a high-cholesterol plus allopurinol (10 mg/kgBW/day) diet or a normal diet. Systolic blood pressure (SBP), serum lipids, uric acid (UA) and malondialdehyde (MDA) as a measure of lipid peroxides, and urinary excretion of protein (UP) were measured after 0, 4 and 8 weeks. Urinary excretion of nitrite plus nitrate (UNOx) and iron (UFe), and MDA in the kidney were measured after 8 weeks. The renal injury was evaluated by the glomerular sclerosis score (SS). The high-cholesterol diet increased SBP, serum total cholesterol and UA, MDA in the serum and kidney, UP, UNOx, UFe and SS. Allopurinol ameliorated cholesterol-induced elevation in serum UA, MDA in the serum and kidney, UP, UNOx, UFe and SS, but did not affect SBP. Hence, our results suggest that lipid peroxidation may be involved in hypercholesterolemia-induced renal injury, and that suppression of lipid peroxidation can reduce such injury.

Topics: Allopurinol; Animals; Blood Pressure; Body Weight; Cholesterol; Creatinine; Enzyme Inhibitors; Heart Rate; Hemodynamics; Hypercholesterolemia; Hypertension; Iron; Kidney; Kidney Diseases; Kidney Function Tests; Male; Malondialdehyde; Nitric Oxide; Proteinuria; Rats; Rats, Sprague-Dawley; Triglycerides; Uric Acid; Xanthine Oxidase

Dosing of allopurinol should be corrected depending on renal function, but corrections based on either plasma creatinine (Pcr) or creatinine clearance (CrCl) have been suggested to be minimal standards of care.. Data from a cohort database of 484 gouty patients were used to calculate estimated allopurinol doses using CrCl and estimation of the clearance of creatinine using the equation of Cockroft and Gault (CrCl-CG) if, as a hypothesis, a dosage of 300 mg/d would be prescribed in any patient with Pcr <2.0 mg/dL. Also, allopurinol-related toxicity previous to rheumatologic consultation, during previous allopurinol therapy, and the relationship between both and estimated allopurinol doses were reviewed.. The cutoff point of plasma creatinine <2 showed 13% sensitivity and 100% specificity to detect CrCl <50 mL/min. Correlation and agreement between CrCl and CrCl-CG were good, as was the correlation between corrected doses using CrCl and CrCl-CG. One third of patients with Pcr 1.0-1.5 mg/dL and 90% of those with Pcr 1.5-2.0 mg/dL would receive estimated doses over 400 mg/dL/d CrCl. Also, 10% and 34% would receive estimated doses over 600 mg/dL/d CrCl, respectively. Allopurinol-related toxicity previous to consultation (11%) was associated with estimated doses over 400 mg/dL/d CrCl and severe toxicity with estimated doses over 600 mg/dL/d CrCl. When patients were given doses corrected on CrCl, few side effects were observed during follow up (6.7%), and the only severe one was associated with corrected dose over 600 mg/d.. Dosage adjustment of allopurinol should be based on clearance of creatinine or estimation of glomerular filtration using the Cockcroft-Gault equation. Pcr is insensitive enough to detect renal function impairment so that patients may be placed at risk for overdosing side effects. Corrected doses over 600 mg/dL/d CrCl may be associated with increased risk of severe toxicity.

Topics: Allopurinol; Creatinine; Databases as Topic; Dose-Response Relationship, Drug; Glomerular Filtration Rate; Gout; Gout Suppressants; Humans; Kidney; Kidney Diseases; Prospective Studies; Sensitivity and Specificity

Topics: Allopurinol; Female; Gout Suppressants; Humans; Hyperuricemia; Kidney Diseases; Male; Mutation; Patient Compliance; Syndrome

Xanthine oxidoreductase (XOR) is the enzyme responsible for the final step in purine degradation resulting in the generation of uric acid. Here we have generated mice deficient in XOR. As expected, these animals lack tissue XOR activity and have low to undetectable serum levels of uric acid. Although normal at birth, XOR-/- mice fail to thrive after 10 to 14 days, and most die within the first month. The cause of death appears to be a form of severe renal dysplasia, a phenotype that closely resembles what has been observed previously in cyclooxygenase-2 (COX-2)-deficient mice. We further demonstrate that in the first month of life, a period in which the mouse kidney is undergoing rapid maturation and remodeling, wild-type mice exhibit an approximately 30-fold increase in renal XOR activity, with a corresponding induction of COX-2 expression. In contrast, during this same period, XOR-/- animals fail to augment renal COX-2 expression. Finally, we show that in vitro and in vivo, uric acid can stimulate basal COX-2 expression. These results demonstrate that XOR activity is an endogenous physiological regulator of COX-2 expression and thereby provide insight into previous epidemiological evidence linking elevated serum uric levels with systemic hypertension and increased mortality from cardiovascular diseases. In addition, these results suggest a novel molecular link between cellular injury and the inflammatory response.

Topics: Animals; Blood Urea Nitrogen; Cyclooxygenase 2; Disease Progression; Enzyme Induction; Female; Genes, Lethal; Genetic Heterogeneity; Hypertension; Inflammation; Kidney; Kidney Diseases; Male; Mice; Mice, Knockout; NIH 3T3 Cells; Phenotype; Prostaglandin-Endoperoxide Synthases; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Gout Suppressants; Humans; Hyperuricemia; Kidney Diseases

Brain death is associated with hemodynamic disturbances in systemic circulation and metabolic storm, and, thus, free radical-mediated injury to donor tissues was hypothesized. An assessment of oxidative stress in the donor and its effect on posttransplant kidney graft function comprised the scope of the study.. A prospective study was performed in 27 donors and 50 kidney transplant recipients. Sera from 27 brain-dead organ donors and preservation media were tested for malondialdehyde (MDA) and for total antioxidant status (TAS). Kidneys were preserved in University of Wisconsin-gluconate solution with machine perfusion. Mean ischemia time was 36.7+/-8 hours. Organs were transplanted to recipients on the Polish National Waiting List and posttransplant kidney function was monitored periodically. Posttransplant delayed graft function (DF) was diagnosed when a patient required at least one dialysis within first week after transplantation. Acute rejection was diagnosed clinically and confirmed with fine-needle biopsy if necessary.. Thirty-two recipients had immediate graft function (IF), and 18 suffered from DF. MDA level in preservation solution at the end of machine perfusion was significantly higher in the DF group (52.6+/-31 vs. 25.3+/-19 micromol/L) whereas donor TAS activity was lower (1.14+/-0.2 vs. 0.97+/-0.3 mmol/mL). Patients who suffered from acute rejection received kidneys from donors with significantly higher serum MDA (66+/-73 micromol/ml vs. 23+/-49 for patients without rejection). Serum creatinine 12 to 48 months after transplantation correlated to donor- and preservation-solution MDA (P<0.006).. Free-radical mediated injury occurring in the donor and during preservation is strictly correlated with immediate and long-term kidney function. It may also cause grafts to be prone to acute rejection.

Topics: Acute Disease; Adenosine; Adolescent; Adult; Aged; Allopurinol; Antioxidants; Brain Death; Creatinine; Female; Free Radicals; Glutathione; Graft Rejection; Humans; Insulin; Kidney; Kidney Diseases; Kidney Transplantation; Male; Malondialdehyde; Middle Aged; Organ Preservation Solutions; Prognosis; Prospective Studies; Raffinose; Time Factors; Tissue Donors

Acute renal failure commonly follows reduced renal perfusion or ischemia. Reperfusion is essential for recovery but can itself cause functional and structural injury to the kidney. The separate contributions of ischemia and of reperfusion were examined in the isolated perfused rat kidney. Three groups were studied: brief (5 min) ischemia, 20 min ischemia, and repetitive brief ischemia (4 periods of 5 min) with repetitive intervening reperfusion of 5 min. A control group had no intervention, the three ischemia groups were given a baseline perfusion of 30 min before intervention and all groups were perfused for a total of 80 min. In addition, the effects of exogenous *NO from sodium nitroprusside and xanthine oxidase inhibition by allopurinol were assessed in the repetitive brief ischemia-reperfusion model. Brief ischemia produced minimal morphological injury with near normal functional recovery. Repetitive brief ischemia-reperfusion caused less functional and morphological injury than an equivalent single period of ischemia (20 min) suggesting that intermittent reperfusion is less injurious than ischemia alone over the time course of study. Pretreatment with allopurinol improved renal function after repetitive brief ischemia-reperfusion compared with the allopurinol-untreated repetitive brief ischemia-reperfusion group. Similarly, sodium nitroprusside reduced renal vascular resistance but did not improve the glomerular filtration rate or sodium reabsorption in the repetitive brief ischemia-reperfusion model. Thus, these studies show that the duration of uninterrupted ischemia is more critical than reperfusion in determining the extent of renal ischemia-reperfusion injury and that allopurinol, in particular, counteracts the oxidative stress of reperfusion.

Topics: Allopurinol; Animals; Disease Models, Animal; Free Radical Scavengers; Glomerular Filtration Rate; Kidney Diseases; Kidney Medulla; Kidney Tubules, Proximal; Male; Natriuresis; Necrosis; Nitroprusside; Rats; Rats, Sprague-Dawley; Reperfusion; Reperfusion Injury; Severity of Illness Index; Vascular Resistance; Vasodilator Agents

Studies on kidney transplantation have thus far mainly dealt with surgical techniques, immunology, and transplant tolerance. Disturbed mineral metabolism after renal denervation has not received much attention. Basic physiological research in short-term experiments has shown that experimental renal denervation in rats leads to parathormone (PTH)-independent hyperphosphaturia (HPU). HPU and other metabolic complications also have been described after clinical kidney transplantation. Furthermore, there is an unexpected increase in the risk of bone fracture. However, these studies have examined an organism pre-damaged with regard to the parathyroid and immunosuppression. Experimental investigations in syngeneic rats were performed to see whether HPU also occurs after transplantation and thus after denervation and which target organs are involved.. Thirty-six male Lewis rats subjected to laparotomy (n = 12), unilateral nephrectomy (n = 12), or unilateral transplantation and bilateral nephrectomy (n = 12) were observed for 18 weeks.. Animals that underwent transplantation had a significant loss of phosphate in the urine not associated with decreased calcium, phosphate, or magnesium in bone. Stability test showed no deterioration, despite a slight increase in the bone parameters of alkaline phosphatase, cyclic AMP, and hydroxyproline with unchanged calciotropic hormones. Nephrocalcinosis was not observed. Parallel to HPU, there was a compensatory reduction in fecal phosphate excretion.. The loss of phosphate after clinical kidney transplantation in the predamaged parathyroid hormone control system as well as immunosuppression and a surprising increase in the incidence of bone fractures may be explained by the denervation-related loss of phosphate. The lack of intestinal counter-regulation could be an important pathomechanism.

Topics: Adenosine; Allopurinol; Animals; Bone and Bones; Calcinosis; Disease Models, Animal; Glutathione; Insulin; Kidney Diseases; Kidney Transplantation; Male; Nephrectomy; Organ Preservation; Organ Preservation Solutions; Phosphates; Raffinose; Rats; Rats, Inbred Lew; Tissue and Organ Harvesting; Transplantation, Isogeneic; Urinalysis

Topics: Allopurinol; Enzyme Inhibitors; Humans; Hyperuricemia; Kidney Diseases; Mucoproteins; Mutation; Uromodulin

The efficacy of allopurinol in autosomal dominant familial juvenile hyperuricaemic nephropathy (FJHN) has been disputed.. To address this question, in the absence of controlled trials.. Retrospective long-term follow-up study.. All kindreds were biochemically screened. Measurements included uric acid clearance, creatinine clearance, serum creatinine, and glomerular filtration rate (GFR). We used five siblings who had died or progressed to transplantation, ten other deceased relatives, and two index cases (one untreated, one non-compliant) as controls to assess the effects of allopurinol.. Of eight families with FJHN, six had a strong history of renal disease and early parental death (mean age 41 years, n=10). Of 27 patients started immediately on allopurinol and treated uninterruptedly, 21 responded well, including three children born subsequently. Eight siblings (mean age 19 years) with a normal plasma creatinine at start (<120 micromol/l, mean GFR 80 ml/min/1.73 m(2)) retained stable renal function (mean 14.5 years, mean age 34 years, GFR 85 ml/min/1.73 m(2)). Of the 13 other responders, treated for up to 34 years, 10 with a creatinine <200 micromol/l at diagnosis (mean age 28 years, mean creatinine 137 micromol/l at start) now have a mean creatinine of 210 micromol/l. In contrast, five patients (mean age 26 years) with a creatinine >200 micromol/l (GFR <35 ml/min/1.73 m(2)) when allopurinol commenced, plus one untreated index case, all progressed rapidly (mean 6 years) to end-stage renal failure. In two others (one non-compliant, one initially untreated), GFR fell by >50% in 7 years. Introduction of allopurinol in the latter has stabilized GFR.. Allopurinol reduced the morbidity and mortality from renal failure seen in untreated siblings and previous generations of these families. Early diagnosis of FJHN is important, so that treatment can begin before irreversible renal damage has developed.

Topics: Adolescent; Adult; Allopurinol; Child; Female; Follow-Up Studies; Gout Suppressants; Humans; Kidney Diseases; Male; Pedigree; Renal Insufficiency; Retrospective Studies; Syndrome; Treatment Outcome; Uremia; Uric Acid; Uricosuric Agents

Topics: Acute Disease; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Benzbromarone; Colchicine; Drug Therapy, Combination; Glucocorticoids; Gout; Gout Suppressants; Humans; Kidney Calculi; Kidney Diseases; Probenecid; Time Factors; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Azathioprine; Biopsy; Diagnosis, Differential; Drug Interactions; Humans; Kidney; Kidney Diseases; Mycophenolic Acid; Uric Acid

We report a 29 years old woman with a chronic tophaceous gout, whose disease started at the age of 18. On clinical examination, the blood pressure was elevated. The laboratory assessment showed a serum uric acid of 15 mg/dl, a urinary uric acid of 155 mg/24 h, a creatinine clearance of 59 ml/min/1.73 m2 and a uric acid excretion fraction off 1.3% (normal 7 to 12%). The clinical and laboratory features of this patient suggest the diagnosis of a familial juvenile gouty nephropathy.

Topics: Adult; Allopurinol; Female; Genetic Counseling; Gout; Gout Suppressants; Humans; Kidney Diseases; Uric Acid

Inhibition of protein synthesis and polyribosome disaggregation are the early events in cell injury provoked by various pathogenic mechanisms, including energy depletion. Polyribosome disaggregation might be expected to occur during ischaemia-reperfusion injury due to ischaemic energy depletion, but also due to detrimental effects of reactive oxygen species on various macromolecules and cellular structures.. Mouse kidney ischaemia-reperfusion injury was provoked by temporary clamping of the renal artery. The polyribosome sedimentation pattern was analyzed by sucrose density centrifugation of kidney postmitochondrial supernatant.. Ischaemia for 5 min in the mouse kidney provoked polyribosome disaggregation and an increase of monomer ribosome fraction which was augmented during 10-360 min of reperfusion. Recovery of polyribosome aggregates appeared between 6 and 24 h of reperfusion. Cycloheximide pretreatment prevented only polyribosome disaggregation caused by ischaemia and not that caused by reperfusion. This indicates different mechanisms of polyribosome disaggregation during ischaemia and reperfusion. It probably occurs in the former due to inhibition of initiation of translation, resulting in accumulation of unprogrammed monomer ribosomes, and in the latter due to the splitting of mRNA and breakdown of polyribosomes. Reperfusion did not increase ribonuclease activity in kidney cytosol, but increased the tissue concentration of malonaldehyde, indicating an augmentation in oxygen free radical generation. Possibly these may have caused a non-enzymatic breakdown of polyribosomes. However, pretreatment with allopurinol did not prevent polyribosome breakdown during ischaemia-reperfusion injury.

Topics: Allopurinol; Animals; Free Radical Scavengers; Free Radicals; Kidney Diseases; Male; Mice; Polyribosomes; Reperfusion Injury

To tabulate data obtained over a 21-year period to determine the efficacy and safety of an intravenous (IV) allopurinol preparation.. IV allopurinol was provided on a compassionate plea basis to patients of any age in whom xanthine oxidase inhibitor therapy was indicated as an adjunct to chemotherapy and for whom oral intake was restricted. Three hundred twenty-seven investigators at multiple hospitals in the United States treated 1,172 patients with IV allopurinol. The vast majority of these patients had a malignancy and were in danger of developing tumor lysis syndrome (TLS) and subsequent acute uric acid nephropathy (AUAN) and were unable to take oral allopurinol. Data referable to the time period of IV allopurinol administration were collected, collated, and analyzed retrospectively. There was no randomization.. In patients initiating treatment for an elevated serum uric acid (SUA), the SUA normalized or improved in 87% of adult patients and normalized or improved in 95% of pediatric patients. IV allopurinol, administered prophylactically to patients at high risk of developing hyperuricemia and TLS, prevented an increase in SUA levels in 93% of adults and 92% of children. Toxicities caused by IV allopurinol were minimal and consisted of 10 instances of mild to moderate skin or allergic reactions.. IV allopurinol is as efficacious and safe as oral allopurinol and will be of significant benefit to patients at risk of TLS and AUAN and unable to take oral medication.

Topics: Adult; Allopurinol; Child; Enzyme Inhibitors; Humans; Infusions, Intravenous; Kidney Diseases; Neoplasms; Tumor Lysis Syndrome; Uric Acid; Xanthine Oxidase

We investigated the relationship between the toxic effect of allopurinol and pyrimidine metabolism in mice. Allopurinol-induced increases in plasma transaminase levels in dinitrofluorobenzene (DNFB)-sensitized mice were not affected by uridine. In contrast, plasma creatinine and BUN tended to decrease 18 hr after the last injection of uridine. Both plasma and urinary orotidine (OD) were detected in DNFB-sensitized mice after administration of a single dose of allopurinol. In contrast, TEI-6720, a newly synthesized xanthine oxidase/xanthine dehydrogenase inhibitor, caused neither pyrimidine metabolism abnormality nor renal impairment in DNFB-sensitized mice. Also, normal mice administered high doses of allopurinol showed abnormal pyrimidine metabolism together with renal toxicity which could be ameliorated by uridine, indicating that allopurinol essentially causes pyrimidine metabolism abnormality leading to renal impairment. In DNFB-sensitized mice, allopurinol increased urinary OD excretion to an extent similar to that in normal mice administered the same dose of allopurinol. However, renal impairment by allopurinol was more striking in DNFB-sensitized mice than in normal mice. Histopathological observations showed that allopurinol induced calculus formation in the collecting tubules and papillary duct. Calculus formation was increased by DNFB and decreased by uridine. These observations indicate that the enhancement of the renal toxicity of allopurinol by DNFB-sensitization may be due to some biological interactions between DNFB and allopurinol. In humans, it is possible that there are some biological interactions which serve to enhance the toxicity of allopurinol, resulting in the development of allopurinol hypersensitivity syndrome (AHS). In contrast, TEI-6720, had no effect on pyrimidine metabolism and showed no toxic effect.

Topics: Allopurinol; Animals; Antimetabolites; Dinitrofluorobenzene; Drug Hypersensitivity; Drug Interactions; Kidney; Kidney Diseases; Male; Mice; Mice, Inbred BALB C; Pyrimidines; Uridine

The therapeutic benefits of allopurinol pretreatment in renal ischaemia-reperfusion injury were investigated by monitoring renal malondialdehyde (MDA) and ATP levels together with calculated MDA/ATP ratio in ischaemic (45 min) and reperfused (15 min) rat kidneys. MDA levels remained unchanged during ischaemia, but increased after the subsequent reperfusion. ATP content of the ischaemic kidney was decreased significantly and the recovery of ATP was incomplete after the reperfusion, whereas the MDA/ATP ratio increased at both periods. Allopurinol pretreatment (40 mg kg(-1) iv) maintained higher ATP levels during the ischaemia and inhibited the MDA formation during the reperfusion and decreased the MDA/ATP ratio at both periods. Our findings demonstrate that allopurinol exerts a biphasic protective action by preserving tissue ATP and by inhibiting lipid peroxidation during ischaemia and the reperfusion period, respectively. These findings suggest the selective involvement of two protective mechanisms in the different periods of renal ischaemia-reperfusion injury. The MDA/ATP ratio could be a useful parameter for monitoring these protective actions of allopurinol simultaneously.

Topics: Allopurinol; Animals; Kidney Diseases; Male; Malondialdehyde; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Topics: Adolescent; Adult; Allopurinol; Child; Child, Preschool; Female; Follow-Up Studies; Gout Suppressants; Humans; Kidney Diseases; Male; Pedigree; Purine-Pyrimidine Metabolism, Inborn Errors; Time Factors; Uric Acid

The role of nitric oxide (NO) and oxygen free radicals in cyclosporine (CsA) nephrotoxicity was investigated using L-arginine, an NO substrate, and allopurinol, a xanthine oxidase inhibitor (involved in the formation of oxygen radicals) in an experimental model with Wistar rats. CsA, administered at 15 mg/kg/body weight (BW) subcutaneously for 10 days, caused a decrease in glomerular filtration rate, with inulin clearance of 0.33+/-0.04 vs. 1.11+/-0.06 ml/min/100 g BW (P<0.01 vs. control). L-Arginine, 1.5% in drinking water 5 days before and during CsA administration, partially protected the animals against this fall in glomerular filtration rate, with inulin clearance of 0.68+/-0.03 ml/min/100 g BW (P<0.01 vs. CsA). Allopurinol, at 10 mg/kg/BW by gavage, also had a protective action, with inulin clearance of 0.54+/-0.04 ml/min/100 g (P<0.01 vs. CsA). CsA caused an elevation in NO production, as assessed by urinary excretion of its metabolites, nitrite and nitrate (NO2 and NO3; 0.836+/-0.358 vs. 0.107+/-0.019 nmol/microg creatinine). NO production was as much as threefold higher in the L-arginine group (1.853+/-0.206 nmol/g creatinine). This CsA effect is probably related to its vasoconstrictive stimulus. Supplementation with L-arginine, which provides more substrate for NO formation, may enhance vasodilatation and consequently reduce the impairment of renal function. The protection provided by allopurinol may be related to the reduced formation of oxygen radicals, preventing the deleterious effects of lipid peroxidation.

Topics: Allopurinol; Animals; Arginine; Cyclosporine; Enzyme Inhibitors; Glomerular Filtration Rate; Inulin; Kidney Diseases; Male; Nitrates; Nitric Oxide; Nitrites; Potassium; Rats; Xanthine Oxidase

Azathioprine is an immunosuppressor used with ciclosporin and corticosteroids after organ transplantation. Azathioprine is rapidly transformed into 6-mercaptopurine which in turn is metabolized by three competitive pathways: a) intracellular hypoxanthine guanine phosphoribosyl transferase leads to 6-thioguanine nucleotides which can damage chromosome DNA; b) thiopurine methyltransferase produces inactive methylated derivatives; c) xanthine oxidase produces thiouric acid. Due to inter-individual variations in the later two pathways, azathioprine dose must be adapted to each patient. A 48-year-old female patient underwent renal transplantation in 1994 and was given immunosuppressive therapy combining thymoglobulins, azathioprine and ciclosporin. Severe leukopenia (< 3000/mm3) occurred on day 5 requiring withdrawal of azathioprine. Known hypouricaemia (< 50 mumol/l) suggested xanthine oxidase deficiency. Laboratory results confirmed xanthine oxidase deficiency and also revealed reduced thiopurine methyltransferase activity (14.9 pmol/h/mg Hb). Azathioprine toxicity was confirmed by regression of the leukopenia after withdrawal and recurrence at rechallenge. Xanthine oxidase deficiency occurs in 2% of the general population. Reduced thiopurine methyltransferase activity affects 11% of the population. The combined presence of these two genetic anomalies led to early and sudden intolerance to azathioprine and emphasize the need to develop new immunosuppressor agents degraded by other metabolic pathways.

Topics: Azathioprine; Female; Humans; Immune Tolerance; Kidney Diseases; Kidney Transplantation; Leukopenia; Middle Aged; Postoperative Complications; Xanthine Oxidase

Recent research suggests the involvement of hydroxyl and superoxide free radicals in the development of gentamicin-induced acute renal tubular necrosis. Xanthine oxidase has been implicated as an important source of superoxide free radicals. Spontaneously hypertensive (Wistar-Kyoto) rats (SHR) have excessive oxidant stress which may render them more sensitive to the proported oxygen free radical producing effects of gentamicin. This study was undertaken to determine if the xanthine oxidase inhibitor allopurinol will ameliorate the effects of gentamicin. Normotensive Wistar-Kyoto (WKY) rats and SHR were administered allopurinol (40 mg/kg twice daily) orally 4 days before and throughout a 12-day gentamicin treatment period. The allopurinol only treatment group demonstrated no noticeable histological or functional changes considered to be indicative of nephrotoxicity. Gentamicin-injected WKY rats and SHR equally demonstrated extensive proximal tubular and glomerular damage characteristic of aminoglycoside-induced kidney damage. Allopurinol failed to protect either rat strain against the histological damage caused by gentamicin. Equivalent alterations in serum creatinine, serum gentamicin, urinary N-acetyl-beta-D-glucosaminidase excretion, body weight, urinary output, and blood pressure occurred in the gentamicin with allopurinol and gentamicin only treatment groups. Our results demonstrate allopurinol does not ameliorate the pathogenesis of gentamicin. SHR do not appear to be more sensitive to the effects of gentamicin induced kidney damage with or without allopurinol as compared with WKY rats.

Topics: Allopurinol; Animals; Gentamicins; Hypertension, Renal; Kidney Diseases; Male; Oxygen; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Urate oxidase, or uricase (EC 1.7.3.3), is a purine metabolic enzyme that catalyzes the conversion of uric acid to allantoin in most mammals except humans and certain other primates. The loss of urate oxidase in the human during primate evolution predisposes man to hyperuricemia, a metabolic disturbance that can lead to gouty arthritis and renal stones. To create a mouse model for hyperuricemia and gout, and to address the question of whether urate oxidase is essential in lower mammalian species, we have disrupted the urate oxidase gene in the mouse by homologous recombination in embryonic stem cells. Unlike the human situation, urate oxidase deficiency in mice causes pronounced hyperuricemia and urate nephropathy. More than half of the mutant mice died before 4 weeks of age, indicating that urate oxidase is essential in mice. These mutant mice may also serve as animal models for hyperuricemia and its related nephropathy in humans.

Topics: Allopurinol; Animals; Arthritis, Gouty; Disease Models, Animal; Genes, Lethal; Humans; Kidney Calculi; Kidney Diseases; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Species Specificity; Urate Oxidase; Uric Acid

We studied urate metabolism in 36 patients undergoing both allogeneic and autologous bone marrow transplantation (BMT) without allopurinol. Most patients had low tumour burdens. Three different preparative regimens were used; busulphan/cyclophosphamide (BUCY); BCNU, etoposide, ara-C and melphalan (BEAM) and cyclophosphamide/total body irradiation (CY/TBI). Urate excretion rose during each of the regimens but the pattern of excretion varied with each regimen. Urate excretion remained elevated 72 h after completion of BEAM and BUCY, possibly reflecting the prolonged action of some of the agents used, e.g. melphalan, busulphan and etoposide. Urinary urate concentrations were unchanged compared with pre-chemotherapy levels reflecting the adequacy of the hydration protocol. No significant rise in creatinine was seen and no cases of tumour lysis syndrome occurred. Serum uric acid levels were a poor reflection of urate production, falling in most patients, and are an unreliable end-point for decisions regarding prophylaxis. BMT can be safely undertaken in patients with low tumour loads without allopurinol if an adequate urine volume is maintained. In this series, high levels of urate excretion often persisted for 72 h after the completion of conditioning and adequate hydration should be ensured during this period.

Topics: Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Humans; Kidney Diseases; Neoplasms; Uric Acid

1. The activity of xanthine oxidase in liver samples of baby pigs up to 4 weeks of age was investigated. On the 3rd day of life the turnover of hypoxanthine and of uric acid were measured after intravenous injection of 3H- and 14C-labelled tracers into animals kept at normal (32 degrees C) and reduced (20 degrees C) ambient temperature. 2. Hepatic xanthine oxidase activity increased progressively from 2 to 28 days of age (r = 0.689; P < 0.001). The increase of Vmax and of KM within 3-4 weeks was about 4.5-fold. 3. In 3-day-old baby pigs kept at normal temperature, pool size and turnover was about 10-fold higher for hypoxanthine than for uric acid. 4. At reduced ambient temperature, the pool size of uric acid increased 3.9-fold (P < 0.01) and turnover 1.6-fold (P < 0.05). For hypoxanthine the increases were insignificant.

Topics: Animals; Animals, Newborn; Cold Temperature; Hypoxanthine; Hypoxanthines; Kidney Diseases; Kinetics; Liver; Purines; Swine; Swine Diseases; Uric Acid; Xanthine Oxidase

The present study was conducted to provide morphological evidence for allopurinol-induced nephrotoxicity in rats and its prevention by the antioxidant butylated hydroxytoluene (BHT). The kidneys of male Sprague Dawley rats fed a diet containing 0.3% allopurinol for 25 days exhibited a marked increase in the weight (2.5 times) as compared to the controls (without allopurinol). Upon microscopic examination, extensive tubulo-interstitial injury leading to structural damage was observed. Feeding BHT (0.4%) along with 0.3% allopurinol brought about a remarkable amelioration of the nephrotoxicity. The results indicate that usage of BHT along with the antiurecemic drug, allopurinol, may be helpful in improving the allopurinol-induced nephrotoxicity observed in some gout patients.

Topics: Allopurinol; Animals; Basement Membrane; Butylated Hydroxytoluene; Kidney; Kidney Diseases; Male; Organ Size; Rats; Rats, Inbred Strains

The efficacy was studied of using allopurinol in 68 patients with primary podagra. The obtained results were compared with the treatment of 118 other patients who received similar treatment but without allopurinol (zanthinoxidase inhibitor). Allopurinol increased essentially the efficacy of therapeutic measures though positive dynamics concerning the renal process was achieved in 1/3 of patients.

Topics: Adult; Aged; Allopurinol; Animals; Disease Models, Animal; Drug Evaluation; Drug Evaluation, Preclinical; Gout; Humans; Kidney Diseases; Male; Middle Aged; Rats; Time Factors

Topics: Adolescent; Adult; Allopurinol; Female; Follow-Up Studies; Gout; Humans; Kidney Diseases; Kidney Transplantation; Male

A kindred is described in which hyperuricemia and renal insufficiency were observed in three generations. The hyperuricemia appeared to precede the renal diseases. Lowering the serum uric acid level to normal did not decrease the progression of renal insufficiency. This suggested that the hyperuricemia was a marker of a familial nephropathy and possibly not the cause.

Topics: Adolescent; Adult; Allopurinol; Gout; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Pedigree; Uric Acid

The present studies show clearly that both dexamethasone and insulin can be omitted without altering the efficacy of UW. Adenosine and glutathione are both helpful additives, as is allopurinol. These findings suggest an important role of reperfusion injury after preservation, and confirm the benefits of adding pharmacological agents likely to reduce this injury. Cold ischemic damage was significantly ameliorated by UW solution in this stringent model of rat kidney preservation for 48 hr. A substantially simplified modification of UW solution has been shown to give equally effective kidney preservation, after removal of hydroxyethyl starch, dexamethasone, and insulin. Adenosine, glutathione, and allopurinol have been confirmed as helpful pharmacological additives. These findings have defined some of the mechanisms of effectiveness of UW solution and suggest avenues of further exploration to improve simple hypothermic storage and to prevent reperfusion injury.

Topics: Adenosine; Allopurinol; Animals; Female; Glutathione; Insulin; Kidney Diseases; Kidney Transplantation; Male; Organ Preservation Solutions; Raffinose; Rats; Rats, Inbred Strains; Reperfusion Injury; Solutions; Tissue Preservation

Patients with acute lymphoblastic leukaemia and a high tumour burden are at risk of developing acute renal failure when given chemotherapy. Rapid cell lysis releases a high urate load which may result in an obstructive urate nephropathy. This complication should be prevented by establishing an alkaline diuresis before initiating steroid or other chemotherapy.

Topics: Adolescent; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Daunorubicin; Diuresis; Humans; Hydrogen-Ion Concentration; Kidney Diseases; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Tumor Lysis Syndrome; Uric Acid; Vincristine

Topics: Allopurinol; Diet Therapy; Female; Food, Formulated; Humans; Kidney Diseases; Male; Temperance; Uric Acid

Topics: Allopurinol; Female; Humans; Kidney Diseases; Kidney Tubules; Male; Metabolic Clearance Rate; Middle Aged; Oxypurinol; Uric Acid

Topics: Allopurinol; Animals; Creatinine; Cyclosporins; Dose-Response Relationship, Drug; Epoprostenol; Ischemia; Kidney; Kidney Diseases; Mannitol; Microscopy, Electron; Rabbits

In order to elucidate toxic and protective mechanisms responsible for allopurinol-induced nephrotoxicity in rats, we investigated changes in plasma creatinine concentration, renal lipid peroxidation, and renal activities of xanthine oxidase, superoxide dismutase and catalase, as enzymatic factors in producing and scavenging oxygen radicals. The rats received subcutaneous injections of allopurinol in a dose of 100 mg/kg body weight, once a day for 3 days. In comparison to the control rats, the following changes were observed in the allopurinol-administered rats: an increase in plasma creatinine concentration, increases in renal contents of malonaldehyde, hypoxanthine and xanthine, and an increase of renal activity of xanthine oxidase, and decreases in renal activities of superoxide dismutase and catalase. Peaks in these changes were observed coincidentally on the third day after the administration of the drug was started. Afterwards, these parameters all returned to the control levels. These results strongly suggested that the allopurinol nephrotoxicity was attributed to the increase of lipid peroxidation which had been caused both by an increase in the ability of producing the oxygen radicals and by a decrease in the ability of scavenging the radicals.

Topics: Allopurinol; Animals; Catalase; Creatinine; Free Radicals; Hypoxanthine; Hypoxanthines; Kidney Diseases; Lipid Peroxides; Male; Organ Size; Oxygen; Rats; Rats, Inbred Strains; Superoxide Dismutase; Xanthine; Xanthine Oxidase; Xanthines

Topics: Aged; Allopurinol; Female; Gout; Humans; Kidney Diseases; Kidney Failure, Chronic; Nephritis, Interstitial; Uric Acid

Topics: Adult; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Colchicine; Female; Gout; Humans; Kidney Diseases; Male; Middle Aged; Sex Factors; Uric Acid

Allopurinol toxicity has been associated with the use of this drug in patients with renal insufficiency, a situation where the half-life of oxipurinol, the major metabolite of allopurinol, is prolonged. Allopurinol toxicity has also been associated with the concomitant use of allopurinol and thiazide diuretics. In the present study, the effect of hydrochlorothiazide administration on the renal clearance and serum half-life of oxipurinol has been studied in eight normal volunteers to determine if thiazides delay the clearance of oxipurinol. Oxipurinol's renal clearance and serum half-life were measured in each volunteer during a control period and again while the volunteer was receiving 50 mg/day hydrochlorothiazide for 1 week. No change in renal oxipurinol clearance (21.1 +/- 5.9 vs. 20.4 +/- 8.7 ml/min) or serum oxipurinol half-life (23.7 +/- 4.2 vs. 23.4 +/- 4.4 hours) was noted with the addition of thiazides. The association previously noted between the use of thiazide diuretics and the development of allopurinol toxicity cannot be explained by alterations in oxipurinol pharmacokinetics.

Topics: Adolescent; Adult; Allopurinol; Diuretics; Drug Evaluation; Drug Interactions; Half-Life; Humans; Hydrochlorothiazide; Kidney; Kidney Diseases; Kidney Function Tests; Oxypurinol; Sodium Chloride Symporter Inhibitors

Topics: Aged; Allopurinol; Autoanalysis; Chlorides; False Negative Reactions; Female; Humans; Kidney Diseases; Male; Middle Aged

A life-threatening toxicity syndrome consisting of an erythematous, desquamative skin rash, fever, hepatitis, eosinophilia, and worsening renal function in 78 patients receiving allopurinol is described. In a majority of cases, the development of this syndrome was associated with the use of standard (200 to 400 mg per day) doses of allopurinol in patients with renal insufficiency. In pharmacologic studies, it was demonstrated that the renal clearance of the major metabolite of allopurinol, oxipurinol, is directly proportional to the renal clearance of creatinine (oxipurinol clearance = 0.22 X creatinine clearance -2.87). An inverse linear relation was noted between the serum oxipurinol half-life and the renal creatinine clearance [( serum oxipurinol half-life in hours]-1 = 0.00034 X creatinine clearance in milliliters per minute + 0.0045). Long-term use of 300 mg per day of allopurinol was found to result in elevated steady-state serum oxipurinol concentrations in patients with renal insufficiency (serum oxipurinol concentration in micromoles per liter = -2.5 X creatinine clearance in milliliters per minute + 326). Avoidance of allopurinol or use of reduced doses in patients with renal insufficiency according to proposed guidelines should be adequate to inhibit uric acid production in most patients and may reduce the incidence of life-threatening allopurinol toxicity.

Topics: Adult; Aged; Allopurinol; Creatinine; Female; Humans; Kidney Diseases; Male; Middle Aged; Syndrome; Uric Acid

It has been recognized that primary disorders of uric acid metabolism result from impaired renal excretion or increased endogenous production of uric acid. It has also been found that these two mechanisms do not comprise two distinct syndromes, but may each constitute a group of syndromes. Contrary to earlier as well as currently published reports we conclude from our clinical and experimental experience that the fraction of so-called over-producers is less than 1% of all patients with primary hyperuricaemia and gout. A procedure for the diagnosis of uric acid overproduction is suggested. The manifestation of hyperuricaemia and gout mainly depends on renal uric acid clearance and is greatly influenced by dietary habits in most of the patients. An impaired renal uric acid excretion results in an increased intestinal excretion; this partly compensates for the defect. Normalization of serum uric acid should be achieved by dietary regimens with or without additional drug treatment, but not by drug treatment alone. With drug treatment xanthine oxidase inhibitors are preferable to uricosurics; no other xanthine oxidase inhibitor besides Allopurinol has been in clinical trial, however. Due to the enhancement of uric acid clearance with uricosurics, there are groups of patients who should not be treated with these drugs. Fixed combinations of Allopurinol and uricosurics should not be used. Drugs which have uricosuric as well as other pharmacologic properties are under investigation. So far they have not reached general clinical application.

Topics: Adult; Diet; Female; Gout; Humans; Hypolipidemic Agents; Kidney Diseases; Male; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Allopurinol; Humans; Kidney Diseases; Male; Middle Aged; Renal Dialysis; Ureteral Obstruction; Uric Acid

Topics: Allopurinol; Antineoplastic Agents; Child; Child, Preschool; Diuresis; Female; Humans; Infant; Kidney Diseases; Leukemia, Lymphoid; Male; Urate Oxidase; Uric Acid

Topics: Allopurinol; Azathioprine; Benzothiadiazines; Cyclophosphamide; Diuretics; Glucocorticoids; Humans; Kidney Calculi; Kidney Diseases; Penicillamine; Phosphates; Sodium Chloride Symporter Inhibitors; Uremia

Topics: Adult; Allopurinol; Bence Jones Protein; Female; Humans; Immunoglobulin D; Immunoglobulin Light Chains; Kidney Diseases; Middle Aged; Multiple Myeloma

Gout may be a primary or a secondary disorder. In both types of gout, overproduction or underexcretion of uric acid, or a combination of these abnormalities, may be the underlying mechanism. Controversy exists over the need for treatment of asymptomatic hyperuricemia. Treatment of tophi requires use of both uricosurics and allopurinol. A xanthine oxidase inhibitor is the drug of choice for patients with uric acid stones and for those with renal insufficiency.

Topics: Allopurinol; Female; Gout; Humans; Kidney; Kidney Diseases; Male; Metabolic Clearance Rate; Middle Aged; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Adolescent; Adult; Allopurinol; Arthritis; Child; Child, Preschool; Gout; Heart Defects, Congenital; Humans; Kidney Diseases; Middle Aged; Uric Acid

Topics: Allopurinol; Colchicine; Diabetes Complications; Gout; Humans; Hypertension; Indomethacin; Kidney Diseases; Obesity; Proteinuria; Socioeconomic Factors; Synovial Fluid; Uric Acid; Urinary Calculi

Topics: Acute Disease; Adolescent; Adult; Aged; Allopurinol; Antineoplastic Agents; Bicarbonates; Drug Therapy, Combination; Female; Fluid Therapy; Humans; Kidney Diseases; Leukemia; Male; Middle Aged; Uremia; Uric Acid

The frequency of severe reactions to allopurinol has probably been underestimated. A retrospective study encompassing a five-year period has yielded 20 patients with severe hypersensitivity reactions to allopurinol. Patients with preexisting renal impairment or who were receiving concomitant thiazide diuretics appeared to be especially predisposed. Cutaneous reaction patterns included maculopapular eruptions, exfoliative dermatitis, and toxic epidermal necrolysis. eosinophilia was uncommon. Forty percent of the patients developed hepatic involvement and 45% had renal involvement. Hepatic and renal changes usually were reversible and were not unique to any one cutaneous reaction pattern. Three patients with renal involvement required prolonged administration of systemic steroids. Complications included sepsis, decubitus ulcers, and thromboembolism. Two patients required hyperalimentation. Sequelae included dry eyes, pigmentary disturbances, and keloids. Three patients died as a result of their reaction. It is concluded that allopurinol should be used only in select patients, and the dosage should be modified if renal disease exists.

Topics: Adult; Aged; Allopurinol; Chemical and Drug Induced Liver Injury; Dermatitis, Exfoliative; Drug Eruptions; Drug Hypersensitivity; Female; Humans; Kidney Diseases; Male; Middle Aged; Prednisone; Retrospective Studies; Stevens-Johnson Syndrome

Topics: Aged; Allopurinol; Chemical and Drug Induced Liver Injury; Drug Eruptions; Drug Hypersensitivity; Humans; Kidney Diseases; Male; Middle Aged; Prednisone; Stevens-Johnson Syndrome

Topics: Acute Disease; Allopurinol; Anti-Inflammatory Agents; Arthritis; Chronic Disease; Colchicine; Gout; Humans; Kidney Diseases; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Gout; Hematologic Diseases; Humans; Kidney Diseases; Uric Acid

Topics: Adult; Allopurinol; Efficiency; Female; Gout; Humans; Kidney Diseases; Male; Middle Aged; Nephrocalcinosis; Prognosis; Synovial Membrane; Uric Acid

Topics: Adult; Allopurinol; Gout; Humans; Kidney Diseases; Middle Aged

The present paper adopts a definite attitude to the differentiated therapy of the disturbances of the uric acid metabolism. This demands an exacter subdivision of the kind of the metabolic disturbance (types Ia, Ib, IIa, IIb, and III). On the basis of this classification in types an individually adapted therapy is possible. It might form the prerequisite of a still more effective meeting of the nephrogenic complications of the gout and of the reduction of the side effects of the necessary permanent therapy.

Topics: Allopurinol; Arteriosclerosis; Citrates; Gout; Humans; Hypertension; Kidney Diseases; Obesity; Phenylbutazone; Uric Acid; Urinary Calculi

Topics: Adult; Allopurinol; Female; Gout; Humans; Infant, Newborn; Kidney Diseases; Pregnancy; Pregnancy Complications

Acute renal failure may be a contributory cause of death in patients with acute leukemia. The purpose of this study was to define the causes and course of acute renal failure in group of patients with acute leukemia in order to identify preventive measures and reversible aspects of the renal insufficiency. Among 88 patients with acute leukemia whose courses were followed to the time of death, ten developed acute renal failure. Etiologic factors of the renal failure were uric acid nephropathy, sepsis with complicating hypotension and hypovolemia, and the administration of nephrotoxic antibiotics. In one patient ureteral obstruction from clots was responsible for renal failure, while in another patient disseminated aspergillosis led to renal failure. Other causes of acute renal failure in persons with acute leukemia, but not observed in this patient group, are hypercalcemia and leukemic infiltration of the kidneys.

Topics: Acute Disease; Acute Kidney Injury; Adult; Allopurinol; Female; Hemorrhage; Humans; Kidney Diseases; Kidney Tubular Necrosis, Acute; Leukemia; Male; Middle Aged; Uric Acid

1. A method of measurement in vitro of purine biosynthesis de novo in human circulating blood lymphocytes is proposed. The rate of early reactions of purine biosynthesis de novo was determined by the incorporation of [14C]formate into N-formyl glycinamide ribonucleotide when the subsequent reactions of the metabolic pathway were completely inhibited by the antibiotic azaserine. 2. Synthesis of 14C-labelled N-formyl glycinamide ribonucleotide by lymphocytes was measured in healthy control subjects and patients with primary gout or hyperuricaemia secondary to renal failure, with or without allopurinol therapy. 3. The average synthesis was higher in gouty patients without therapy than in control subjects, but the values obtained overlap the normal range. In secondary hyperuricaemia the synthesis was at same value as in control subjects. 4. These results are in agreement with the inconstant acceleration of purine biosynthesis de novo in gouty patients as seen by others with measurement of [14C]glycine incorporation into urinary uric acid.

Topics: Adult; Allopurinol; Female; Gout; Humans; In Vitro Techniques; Kidney Diseases; Lymphocytes; Male; Middle Aged; Purines; Ribonucleotides; Uric Acid

Topics: Adult; Aged; Allopurinol; Chemical and Drug Induced Liver Injury; Drug Eruptions; Drug Hypersensitivity; Humans; Inflammation; Kidney Diseases; Male; Middle Aged; Vascular Diseases

Topics: Adenine; Allopurinol; Animals; Body Weight; Caseins; Dietary Proteins; Kidney; Kidney Diseases; Kidney Tubules; Liver; Male; Organ Size; Rats; Urine; Xanthine Oxidase

Topics: Allopurinol; Animals; Chemical and Drug Induced Liver Injury; Drug Eruptions; Gastrointestinal Diseases; Haplorhini; Hematologic Diseases; Humans; Kidney Diseases; Muscular Diseases; Neuritis

Topics: Allopurinol; Emergencies; Humans; Kidney Diseases; Leukemia; Mannitol; Peritoneal Dialysis; Renal Dialysis; Uric Acid

Asymptomatic hyperuricemia should be treated only if the plasma uric acid levels are around 10 mg/100 ml or more on several determinations. In addition, patients on a purine-free diet who excrete more than 600 mg uric acid per 24 h should be treated. In both cases, treatment is intended to be prophylactic against gouty nephropathy. At present there is no evidence that primary hyperuricemia alone is a risk factor for early atherosclerosis and especially coronary artery disease. However, more attention should be paid to the accompanying risk factors such as obesity, hyperlipoproteinemia, diabetes mellitus and hypertension.

Topics: Allopurinol; Benzbromarone; Citrates; Coronary Disease; Gout; Humans; Hyperlipidemias; Hypertension; Hypoxanthine Phosphoribosyltransferase; Kidney Diseases; Lesch-Nyhan Syndrome; Obesity; Uric Acid

Hyperuricemia and gout has been recognized among the Filipinos in Hawaii, Alaska, and mainland United States for almost two decades. Several studies bearing out this impression have been reviewed. The awareness of these observation prompted an extension to the Filipino in his natural environment. These studies showed a lower mean of serum uric acid values in healthy subjects when using comparative enzymatic spectrophotometric determinations. Aside from genetic factors, Filipino hyperuricemia may become manifest because of environmental stress, including dietary stress, and investigators postulate that some Filipinos possess a renal defect that may lead to hyperuricemia due to renal inability to compensate for an increased purine intake which may occur in the shift from a low-purine Filipino diet to a high-purine Western diet in his new environment, as in the case of the Filipino immigrant. The clinical profile of gout as it exists in the Philippines has been compared and found to be similar generally to that of other series. The control of the hyperuricemia and gout has been satisfactorily accomplished in the Filipino patients with the long-term use of allopurinol, sometimes complemented with colchicine taken daily.

Topics: Adolescent; Adult; Age Factors; Aged; Allopurinol; Cross-Cultural Comparison; Diet; Ethnicity; Female; Gout; Humans; Kidney Diseases; Male; Middle Aged; Philippines; Purines; Recurrence; Sex Factors; United States; Uric Acid

Topics: Allopurinol; Antineoplastic Agents; Anuria; Bicarbonates; Child; Child, Preschool; Disseminated Intravascular Coagulation; Electrolytes; Humans; Kidney Diseases; Leukemia; Nucleic Acids; Prednisone; Purines; Uric Acid; Vincristine; Xanthines

Topics: Adult; Aged; Allopurinol; Female; Gout; Humans; Kidney Diseases; Male; Middle Aged; Uric Acid

Topics: Allopurinol; Aspirin; Binding Sites; Blood Proteins; Colchicine; Dialysis; Evaluation Studies as Topic; Gout; Humans; Hydrogen-Ion Concentration; Indomethacin; Kidney Diseases; Kinetics; Methods; Osmolar Concentration; Phenylbutazone; Probenecid; Protein Binding; Serum Albumin; Solubility; Sulfinpyrazone; Temperature; Time Factors; Uric Acid

Topics: Allopurinol; Amino Acids; Aspirin; Autoanalysis; Creatinine; Glycosuria; Humans; Kidney Diseases; Neoplasms; Phosphates; Porphobilinogen; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Salicylates; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Bence Jones Protein; Drug Therapy, Combination; Female; Humans; Kidney Diseases; Male; Melphalan; Multiple Myeloma; Myeloma Proteins; Prednisone; Proteinuria

Topics: Allopurinol; Arthritis; Calcium Phosphates; Cartilage, Articular; Chondrocalcinosis; Crystallization; Diphosphates; Gout; Humans; Kidney Diseases; Kidney Tubules; Leukocytes; Macrophages; Myeloproliferative Disorders; Synovial Fluid; Uric Acid

Topics: Adult; Aged; Allopurinol; Creatinine; Female; Glomerular Filtration Rate; Gout; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Uric Acid

Topics: Allopurinol; Analgesics; Arteriosclerosis; Blood Platelets; Colchicine; Diabetes Complications; Gout; Halofenate; Humans; Hyperlipidemias; Hypertension; Hypoxanthines; In Vitro Techniques; Kidney Diseases; Uric Acid; Uricosuric Agents; Vascular Diseases; Xanthines

Topics: Allopurinol; Arteriosclerosis; Blood Protein Disorders; Citrates; Colchicine; Diabetes Mellitus; Diet Therapy; Gout; Humans; Hyperlipidemias; Hypertension; Kidney Calculi; Kidney Diseases; Phenylbutazone; Physical Therapy Modalities; Time Factors; Uremia; Uric Acid

Topics: Allopurinol; Animals; Crystallization; Disease Models, Animal; Gout; Guanine; Kidney Diseases; Swine

Topics: Allopurinol; Citrates; Diet Therapy; Gout; Humans; Kidney Calculi; Kidney Diseases; Uricosuric Agents

Topics: Allopurinol; Humans; Kidney Diseases; Leukemia; Uric Acid

Topics: Aged; Allopurinol; Animals; Diabetes Mellitus; Gout; Humans; Hydrogen-Ion Concentration; Hypercholesterolemia; Hypertension; Hypoxanthines; Kidney Calculi; Kidney Diseases; Kidney Failure, Chronic; Swine; Uremia; Uric Acid; Xanthenes; Xanthine Oxidase

Topics: Allopurinol; Animals; Desoxycorticosterone; Estradiol; Ethylestrenol; Female; Kidney; Kidney Diseases; Oxandrolone; Prednisolone; Pregnanediones; Progesterone; Rats; Spironolactone; Triamcinolone

Topics: Allopurinol; Diabetes Mellitus; Diet Therapy; Gout; Humans; Kidney Diseases; Metabolic Diseases; Uric Acid; Uricosuric Agents; Vascular Diseases

Topics: Animals; Biochemistry; Creativity; History, 20th Century; Hyperplasia; Hypertrophy; Hypoxanthines; Kidney; Kidney Diseases; Mitosis; Pteridines; Purines; Pyrazines; Pyrimidines; Quinoxalines; Rats; Stimulation, Chemical; Structure-Activity Relationship; United Kingdom; Xanthine Oxidase; Xanthopterin

Topics: Acenocoumarol; Allopurinol; Chloramphenicol; Chlorpropamide; Clofibrate; Glomerular Filtration Rate; Glomerulonephritis; Half-Life; Humans; Kidney; Kidney Diseases; Probenecid; Pyelonephritis

Topics: Adolescent; Adult; Aged; Allopurinol; Anti-Bacterial Agents; Antihypertensive Agents; Female; Gout; Humans; Kidney Calculi; Kidney Diseases; Male; Middle Aged; Nephritis, Interstitial; Nephrosclerosis; Pyelonephritis; Uric Acid; Uricosuric Agents

Topics: Adult; Allopurinol; Colchicine; Diet Therapy; Female; Gout; Humans; Kidney Diseases; Male; Middle Aged; Oxyphenbutazone; Phenylbutazone; Probenecid; Sulfinpyrazone; Uric Acid

Topics: Allopurinol; Chloramphenicol; Chlorpropamide; Chromium Isotopes; Humans; Kidney Diseases; Probenecid

Topics: Allopurinol; Citrates; Colchicine; Gout; Humans; Indomethacin; Kidney Calculi; Kidney Diseases; Nephrosclerosis

Topics: Allopurinol; Autopsy; Burkitt Lymphoma; Child; Cyclophosphamide; Humans; Kidney; Kidney Diseases; Male; Orotic Acid; Purines; Renal Dialysis; Uric Acid; Xanthines

Topics: Adolescent; Athetosis; Brain; Child; Child, Preschool; Compulsive Behavior; Gout; Humans; Huntington Disease; Infant; Infant, Newborn; Intellectual Disability; Kidney Diseases; Liver; Prognosis; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Self Mutilation; Transferases; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Animals; Chemical and Drug Induced Liver Injury; Chickens; Dietary Proteins; Hypertrophy; Kidney; Kidney Diseases; Kidney Function Tests; Liver; Male; Potassium; Protein Biosynthesis; Time Factors; Uric Acid; Xanthine Oxidase

Topics: Acidosis, Renal Tubular; Acute Kidney Injury; Aged; Allopurinol; Amyloidosis; Bence Jones Protein; Blood Viscosity; Bone Neoplasms; Diuretics; Humans; Hypercalcemia; Kidney; Kidney Diseases; Middle Aged; Multiple Myeloma; Myeloma Proteins; Pyelonephritis; Uremia; Uric Acid

Topics: Allopurinol; Azathioprine; Blood Cell Count; Bone Marrow; Bone Marrow Diseases; Drug Interactions; Humans; Hypertension; Kidney Diseases; Male; Middle Aged

Topics: Adolescent; Aged; Allopurinol; Colic; Female; Gout; Humans; Kidney Diseases; Male; Middle Aged; Sulfinpyrazone; Uric Acid

Topics: Adenine; Adult; Age Factors; Allopurinol; Enzyme Repression; Female; Gout; Guanine; Humans; Hypoxanthines; Kidney Calculi; Kidney Diseases; Male; Pedigree; Transferases; Uric Acid; Xanthines

Topics: Allopurinol; Humans; Kidney; Kidney Calculi; Kidney Diseases; Uric Acid

Topics: Aminohydrolases; Drug Stability; Erythrocytes; Fingers; Guanine; Hepatitis A; Humans; Kidney Diseases; Spectrophotometry; Uric Acid; Xanthine Oxidase

Topics: Adolescent; Adult; Allopurinol; Diet Therapy; Diet, Sodium-Restricted; Diuretics; Gout; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Tubules; Male; Piperazines; Proteinuria; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid

Topics: Allopurinol; Diabetes Mellitus; Gout; Humans; Hypertension; Kidney Diseases; Male; Sulfinpyrazone; Uric Acid

Topics: Adult; Allopurinol; Gout; Humans; Kidney Diseases; Kidney Diseases, Cystic; Male; Uremia

Topics: Adult; Aged; Allopurinol; Disease Susceptibility; Gout; Humans; Kidney Calculi; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Uric Acid

Topics: Acetazolamide; Acute Disease; Adolescent; Allopurinol; Bicarbonates; Blood Urea Nitrogen; Child; Creatinine; Humans; Kidney Diseases; Leukemia, Lymphoid; Leukocyte Count; Male; Mannitol; Prednisone; Renal Dialysis; Uric Acid

Topics: Allopurinol; Colchicine; Crystallization; Diagnosis, Differential; Diet Therapy; Gout; Humans; Indomethacin; Joint Diseases; Kidney Diseases; Kidneys, Artificial; Phenylbutazone; Probenecid; Proteinuria; Purines; Radiography; Salicylates; Steroids; Sulfinpyrazone; Uric Acid

Topics: Adult; Aged; Allopurinol; Female; Gout; Humans; Kidney Diseases; Kidney Function Tests; Male; Methods; Middle Aged; Time Factors; Uric Acid

Topics: Allopurinol; Guanine; Humans; Hypoxanthines; Intellectual Disability; Kidney Diseases; Metabolism, Inborn Errors; Nervous System Diseases; Sex Chromosomes; Transferases; Uremia; Uric Acid; Xanthine Oxidase

Topics: Adult; Aged; Allopurinol; Child; Diuretics; Female; Gout; Humans; Kidney Diseases; Kidney Failure, Chronic; Leukemia; Male; Metabolic Clearance Rate; Middle Aged; Myeloproliferative Disorders; Uremia; Uric Acid

Topics: Adenosine Triphosphate; Allopurinol; Anemia; Brain Diseases; Carbon Isotopes; Child, Preschool; Erythrocytes; Fibroblasts; Humans; Infant; Intellectual Disability; Kidney Diseases; Male; Metabolism, Inborn Errors; Purines; Self Mutilation; Transferases; Uric Acid

Topics: Age Factors; Aged; Allopurinol; Bone and Bones; Cardiovascular Diseases; Colchicine; Female; Gout; Humans; Hyperlipidemias; Hypertension; Kidney Diseases; Male; Probenecid; Sodium; Sulfinpyrazone; Uric Acid

Topics: Allopurinol; Anti-Infective Agents; Diagnosis, Differential; Gout; Kidney Diseases; Uricosuric Agents

Topics: Allopurinol; Gout; Humans; Kidney Diseases; Uric Acid; Xanthine Oxidase

Topics: Adolescent; Aged; Enzyme Therapy; Humans; Kidney Diseases; Leukemia; Male; Purines; Pyrazoles; Pyrimidines; Uric Acid; Xanthine Oxidase

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Enzyme Therapy; Female; Gout; Humans; Kidney Diseases; Leukemia; Lymphoma; Male; Middle Aged; Uric Acid; Urinary Calculi; Xanthine Oxidase

Topics: Allopurinol; Blood Urea Nitrogen; Enzyme Therapy; Female; Gout; Humans; Kidney Calculi; Kidney Diseases; Male; Salicylates; Sulfinpyrazone; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Enzyme Therapy; Gout; Humans; Kidney Diseases; Renal Dialysis; Xanthine Oxidase