allopurinol and Kidney-Failure--Chronic

Chronic kidney disease (CKD) is a common condition that has become a significant public health concern. The mainstay therapeutic approach to CKD is based on renin-angiotensin system blockade as well as blood pressure and glycemic control. Despite these interventions, the management of CKD remains suboptimal, with a large proportion of the CKD population progressing to end-stage renal disease. Newer strategies for the treatment of CKD have emerged over the past years focusing on decreasing inflammation and delaying the development of fibrosis. Despite promising results in experimental models and small randomized studies, adequately powered randomized trials are required to evaluate the benefits and risks of these therapies in the CKD population. In this review, we discuss the evidence behind, and gaps in our knowledge of, established therapies as well as newer potential strategies for managing CKD, concentrating on interventions that currently are being evaluated in randomized studies.

Topics: Allopurinol; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Bicarbonates; Diabetes Mellitus; Diabetic Nephropathies; Disease Progression; Endothelin Receptor Antagonists; Ergocalciferols; Free Radical Scavengers; Glycated Hemoglobin; Gout Suppressants; Humans; Hypertension; Hyperuricemia; Hypoglycemic Agents; Kidney Failure, Chronic; Mineralocorticoid Receptor Antagonists; Pentoxifylline; Pyridoxamine; Renal Insufficiency, Chronic; Vitamin B Complex

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common form of primary glomerulopathy worldwide. Various investigations have addressed the clinical and morphological risk factors related to the risk of progression. Recently, much attention has been made toward the prognostic implication of serum uric acid in patients with IgAN. It has been observed that treatment of hyperuricemia with allopurinol in chronic kidney failure has resulted in a fall in blood pressure and inhibition of the progression of kidney injury. Recent studies have documented that hyperuricemia is an independent risk factor for IgAN, and appropriate treatment by allopurinol is a reasonable modality in these patient. We believe that allopurinol should routinely be included to the treatment of IgAN patients; however, this hypothesis requires further investigation. Clinical studies are suggested to better understand kidney protective properties of allopurinol in IgAN.

Topics: Allopurinol; Disease Progression; Glomerulonephritis, IGA; Gout Suppressants; Humans; Hyperuricemia; Kidney; Kidney Failure, Chronic; Risk Factors; Treatment Outcome; Uric Acid

Observational studies have shown that asymptomatic hyperuricemia is associated with increased risks of hypertension, chronic kidney disease (CKD), end-stage renal disease, cardiovascular events, and mortality. Whether these factors represent cause, consequence or incidental associations, however, remains uncertain. Hyperuricemia could be a consequence of impaired kidney function, diuretic therapy or oxidative stress, such that elevated serum urate level represents a marker, rather than a cause, of CKD. On the other hand, small, short-term, single-center studies have shown improvements in blood-pressure control and slowing of CKD progression following serum urate lowering with allopurinol. An adequately powered randomized controlled trial is required to determine whether uric-acid-lowering therapy slows the progression of CKD. This article discusses the rationale for and the feasibility of such a trial. International collaboration is required to plan and conduct a large-scale multicenter trial in order to better inform clinical practice and public health policy about the optimal management of asymptomatic hyperuricemia in patients with CKD.

Topics: Allopurinol; Gout Suppressants; Humans; Hyperuricemia; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Research Design; Risk Factors; Uric Acid

Topics: Allopurinol; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Chondrocalcinosis; Comorbidity; Diabetes Mellitus, Type 2; Febuxostat; Gout; Gout Suppressants; Guideline Adherence; Humans; Hypertrophy, Left Ventricular; Hyperuricemia; Interleukin 1 Receptor Antagonist Protein; Kidney Failure, Chronic; Thiazoles; Xanthine Oxidase

Many patients with gout have comorbidities, including hypertension and chronic kidney disease (CKD). The goals when treating gout are no different in these patients, but the choice and dosage of drugs may need to be modified.

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Comorbidity; Disease Progression; Febuxostat; Gout; Gout Suppressants; Humans; Kidney Failure, Chronic; Risk Factors; Thiazoles

Topics: Allopurinol; Antimetabolites; Glomerulonephritis; Humans; Hyperuricemia; Hypoxanthine; Kidney; Kidney Failure, Chronic; Purines; Renal Dialysis; Uric Acid; Xanthine

To review the current understanding of the causes and the management of gout.. Publications on all peer-review literature from MEDLINE from 1965 to January 2004.. Selected and evaluated by the author.. Extracted and evaluated by the author.. The underlying metabolic disorder in gout is hyperuricaemia. Most patients with hyperuricaemia remain asymptomatic throughout their lifetime. The phase of asymptomatic hyperuricaemia ends with the first attack of gouty arthritis or urolithiasis. The risk of gout and stone formation is increased with the degree and duration of hyperuricaemia. Drugs available for the treatment of acute gouty arthritis, such as non-steroidal anti-inflammatory drugs, selective cyclo-oxygenase 2 inhibitors, systemic corticosteroids, or colchicine, are effective. For periods between attacks, prophylactic therapy, such as low-dose colchicine, is effective. In those with recurrent attacks of more than two to three times yearly, a uric acid-lowering agent as a long-term therapy should be considered to avoid recurrence and the development of tophaceous gout.. Effective management of gout can be achieved through better understanding of the causes of the condition, preventive measures as well as drug treatment.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Colchicine; Cyclooxygenase Inhibitors; Diet Therapy; Female; Gout; Gout Suppressants; Heart Failure; Humans; Hyperuricemia; Kidney Failure, Chronic; Male; Purines; Xanthine Oxidase

Adenine phosphoribosyltransferase(APRT) deficiency is an autosomal recessive disorder and the homozygotes develop 2,8-dihydroxyadenine(DHA) urolithiasis and, in severe cases, renal failure. The prevalence is higher among the Japanese than other ethnic groups. So far 120 cases have been reported among the Japanese. The disease is classified into 2 types; type I and II are associated with complete and partial deficiencies, respectively. While all non-Japanese cases were of type I, about 78% of the Japanese patients were of type II. Each of the type II patients has at least one APRT*J allele with a ATG(Met) to ACG(Thr) base substitution at codon 136. All APRT*J alleles were derived from a single ancestor. All type I patients and some type II patients possess APRT*QO alleles with various point mutations or large gene abnormality. Type II patients tend to develop first symptoms later than the type I patients. The diagnoses of homozygotes and heterozygotes can be done by the cell culture methods. Both enzyme assay and molecular diagnostic methods are useful but not as reliable as the cell culture methods Excessive water intake, restriction of foods with high adenine contents and administration of allopurinol are useful treatments.

Topics: Adenine; Adenine Phosphoribosyltransferase; Alleles; Allopurinol; Heterozygote; Homozygote; Humans; Kidney Failure, Chronic; Nucleic Acid Hybridization; Point Mutation; Polymerase Chain Reaction; Urinary Calculi

Topics: Allopurinol; Gout; Humans; Kidney; Kidney Failure, Chronic; 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

Topics: Allopurinol; Aluminum; Anemia; Antihypertensive Agents; Blood Transfusion; Bone Diseases; Diet Therapy; Diet, Sodium-Restricted; Diuretics; Humans; Hydroxides; Hypertension; Kidney Failure, Chronic; Palliative Care; Parathyroid Glands; Uric Acid; Vitamin D

Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD.. Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2. 20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 (. Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view.. NCT03470454.

Topics: Acetylcysteine; Acute Kidney Injury; Allopurinol; Chemoprevention; Contrast Media; Diabetic Nephropathies; Drug Therapy, Combination; Humans; Kidney Failure, Chronic; Linagliptin; Prospective Studies; Protective Agents; Renal Insufficiency, Chronic; Saline Solution

Chronic kidney disease (CKD)-mineral and bone disorder (MBD) is a systemic disorder that leads to vascular calcification and accelerated atherosclerosis. Uric acid has been shown to associate with vascular calcification and with carotid intima-media thickness (CIMT) and to suppress the 1 α-hydroxylase enzyme leading to lower 1,25-dihydroxyvitamin D (1,25(OH)2D) and higher intact parathyroid hormone (iPTH) levels. We hypothesized that lowering serum uric acid would reduce CIMT, calcification propensity, and circulating markers of CKD-MBD in CKD.. This is a post-hoc analysis of a randomized, double-blind study of 80 patients with stage 3 CKD and hyperuricemia who received allopurinol or placebo for 12 weeks. CIMT and T50 were measured as markers of vascular disease and serum calcification propensity, respectively. The following markers of CKD-MBD were measured: serum calcium, phosphorus, vitamin D metabolites, iPTH, and fibroblast growth factor-23 (FGF-23). Expression of extra-renal 1α-hydroxylase was evaluated in endothelial cells of study participants.. Allopurinol successfully lowered serum uric acid levels compared to placebo with an estimate of -3.3 mg/dL (95% C.I. -4.1,-2.5; p < 0.0001). After 12 weeks, however, we found no significant change in CIMT or serum T50. There was not a significant change in vitamin D metabolites, iPTH, FGF-23, or the expression of endothelial 1α-hydroxylase.. These data suggest that factors other than uric acid may play a more important role in the regulation of CKD- MBD including vascular calcification and vitamin D metabolism in patients with CKD.

Topics: Adolescent; Adult; Aged; Allopurinol; Carotid Intima-Media Thickness; Chronic Kidney Disease-Mineral and Bone Disorder; Double-Blind Method; Female; Fibroblast Growth Factor-23; Humans; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Renal Insufficiency, Chronic; Uric Acid; Vascular Calcification; Vitamin D; Young Adult

Endothelial dysfunction is an important risk factor for cardiovascular diseases to occur in end-stage renal disease patients. Febuxostat, being a novel xanthine oxidase inhibitor, is apparently having a beneficial role in improving the endothelial dysfunction; however, data among hemodialysis patients are still limited.. A prospective, placebo-controlled, block-randomized, double-blinded study was carried out to evaluate the effect of oral febuxostat on the endothelial dysfunction in hemodialysis patients. Fifty-seven eligible hemodialysis patients were randomly assigned to either the drug group (40 mg thrice weekly) or the placebo group. Serum Asymmetric dimethylarginine (ADMA), Serum uric acid (UA), and serum high sensitivity C-reactive protein (hsCRP) were measured at baseline and at the end of a 2-month study. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and the occurrence of pancytopenia were tested as safety parameters at baseline and at the end of study.. Serum UA significantly decreased from 7.5 ± 0.8 to 5.1 ± 1.2 mg/dL in the febuxostat group, while it did not change significantly in the placebo group. Treatment with febuxostat resulted in a significant decrease in the serum ADMA level from 1.027 ± 0.116 to 0.944 ± 0.104 µmol/L and the serum hsCRP level from 12.5 ± 1.65 to 12.1 ± 1.70 mg/L. Testing of serum ALT, serum AST, and pancytopenia revealed no significant difference in both groups.. Febuxostat appears to improve hyperuricemia and endothelial dysfunction and ameliorate inflammation in hemodialysis patients with no safety concerns.

Topics: Administration, Oral; Adult; Alanine Transaminase; Arginine; Aspartate Aminotransferases; C-Reactive Protein; Cardiovascular Diseases; Double-Blind Method; Endothelium, Vascular; Enzyme Inhibitors; Febuxostat; Female; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Pancytopenia; Placebos; Prospective Studies; Renal Dialysis; Risk Factors; Treatment Outcome; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme Inhibitors; Female; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; 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

Although the University of Wisconsin (UW) has become the standard solution for the preservation of kidneys for transplantation, the importance of the colloid hydroxyethylstarch (HES), one of the key compounds of the UW solution, has been judged controversial. It has been shown in various experimental models that dextran-40 may successfully substitute for HES. Dextran-40 is not only cheaper but also has a variety of biological effects which may be beneficial during the graft reperfusion phase. The aim of this clinical study was to examine the efficiacy of dextran-40 based preservation solution (Dex-PS) for its use for human kidney graft preservation and to compare the transplantation results with kidneys preserved with UW solution. A total of 87 kidneys were preserved with Dex-PS and matched with 87 kidneys preserved with UW solution. Both groups were comparable in terms of donor and recipients characteristics. Patient survival and graft survival after 1 year was 95% and 86% for the Dex-PS group and 94% and 90% for the UW group, respectively (p = n.s.). Primary non-function, delayed graft function, postoperative need for dialysis, and follow-up of serum creatinine were statistically comparable between these two groups. We conclude that dextran-40 can safely replace HES in the UW solution for the purpose of human kidney preservation for transplantation. There were no statistically detectable differences in graft performance between the kidneys preserved with UW and those preserved with Dex-PS.

Topics: Adenosine; Adult; Allopurinol; Dextrans; Female; Follow-Up Studies; Glutathione; Graft Survival; Humans; Insulin; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Organ Preservation; Organ Preservation Solutions; Raffinose; Treatment Outcome

Topics: Adenosine; Allopurinol; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Glutathione; Humans; Hypertonic Solutions; Insulin; Kidney Failure, Chronic; Kidney Transplantation; Organ Preservation; Organ Preservation Solutions; Pancreas; Pancreas Transplantation; Postoperative Complications; Raffinose; Retrospective Studies; Thrombosis

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

Recent studies have demonstrated negative associations of serum uric acid (SUA) with serum 25 hydroxy vitamin D (25 [OH] vit D) among CKD patients.. The aim of the study was to look for the impact of hypouricemic therapy using allopurinol on serum level of 25 (OH) vit D in CKD patients.. Seventy-two CKD stage 3-5 patients were selected to this study. Patients with SUA above 7 mg/dL were allocated to hypouricemic therapy using allopurinol (group I). A control group of cases not suffering marked increase in SUA were included as control group (group II). All cases were followed up for 3 months. Serum Cr, SUA, ionized calcium (SiCa), phosphorus, 25 (OH) vitD, parathyroid hormone (PTH), and 24-h urine protein were estimated at entry and by the end of the study.. At least 20 cases completed the study in each group. Serum 25 (OH) vit D significantly increased in group I (26.4 [14.1] vs. 39.6 [14.8] at entry vs. at end of the study, p < 0.001). In addition, SUA, PTH, and urine protein significantly decreased (11 [1.6] vs. 3.95 [0.58] mg/dL, 267.5 [97.5] vs. 225.5 [153] ng/mL, and 2.7 [1.18] vs. 1.5 [1.08] gm/day, p < 0.001, = 0.043, and <0.001 respectively). SiCa and phosphorus significantly increased (4.4 [0.3] vs. 5.2 [0.5] mg/dL and 4.25 [0.72] vs. 4.9 [0.75] mg/dL, p < 0.001 and = 0.007, respectively).. This study supports a negative causal relationship between SUA and serum 25 (OH) vit D. Further studies are still needed to confirm this conclusion.

Topics: Adult; Allopurinol; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pilot Projects; Uric Acid; Vitamin D

Hyperuricemia is highly prevalent in chronic kidney disease (CKD) patients, but the evidence for a relationship between uric acid (UA) and clinical outcomes in CKD patients is limited and inconsistent. We hypothesized that UA has a different impact on clinical outcomes according to the underlying disease causing CKD.. This study prospectively investigated the associations between UA and renal and non-renal outcomes according to the underlying disease causing CKD in 2,797 Japanese patients under the care of nephrologists. The patients were categorized into four groups: primary renal disease (n = 1306), hypertensive nephropathy (n = 467), diabetic nephropathy (n = 275), and other nephropathy (n = 749). The renal outcome was defined as end-stage renal disease (ESRD), and the non-renal outcome was defined as a composite endpoint of cardiovascular events (CVEs) and all-cause mortality.. During a median 4.8-year follow-up, 359 (12.8%) patients reached the renal outcome, and 260 (9.3%) reached the non-renal outcome. In the all-patient analysis, hyperuricemia was not associated with the risks for renal and non-renal outcomes, but in primary renal disease (PRD) and hypertensive renal disease (HTN) patients, hyperuricemia was significantly associated with non-renal outcomes. Per 1 mg/dl higher UA level, multivariable adjusted hazard ratio was 1.248 (95% CI: 1.003 to 1.553) for PRD, and 1.250 (1.035 to 1.510) for HTN. Allopurinol did not reduce the risks for renal and non-renal outcomes, both in all patients and in the subgroup analysis.. The effect of hyperuricemia on clinical outcomes in CKD patients varies according to the underlying disease causing CKD. Hyperuricemia is an independent risk factor for non-renal outcomes in primary renal disease and hypertensive renal disease patients. Allopurinol did not decrease the risks for renal and non-renal outcomes.

Topics: Adult; Aged; Allopurinol; Antimetabolites; Female; Glomerular Filtration Rate; Humans; Hyperuricemia; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Renal Insufficiency, Chronic; Risk; Severity of Illness Index; Uric Acid

Adenine phosphoribosyltransferase (APRT) deficiency is a rare, hereditary cause of kidney stones and chronic kidney disease (CKD) which is characterized by 2,8-dihydroxyadenine renal parenchymal crystal deposition. The aim of this study was to examine outcomes of kidney transplantation in APRT deficiency patients.. Included were 13 patients in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, 2 from Westmead Hospital in Sydney, Australia, and 2 from Necker Hospital in Paris, France. The CKD-EPI and CKiD equations were used to calculate glomerular filtration rate estimates. Allograft survival was analyzed employing the Kaplan-Meier method. The Wilcoxon-Mann-Whitney test was used to compare alllograft outcomes according to xanthine oxidoreductase (XOR) inhibitor treatment status at transplantation.. Seventeen patients (9 females) received 22 kidney transplants. Age at first transplantation was 47.2 (14.9-67.0) years. Ten patients received XOR inhibitor therapy pretransplant (11 allografts), while 8 patients did not receive such treatment before transplantation (11 allografts). Two-year allograft survival was 91% and 55% in the 2 groups, respectively (P = 0.16). The median (range) estimated glomerular filtration rate at 2 years posttransplant was 61.3 (24.0-90.0) mL/min/1.73 m when XOR inhibitor therapy was initiated before transplantation, and 16.2 (10.0-39.0) mL/min/1.73 m (P = 0.009) when such treatment was not administered pretransplant.. Kidney allograft outcomes are good in APRT deficiency patients beginning XOR inhibitor therapy pretransplant. Delay in such treatment is a major cause of premature graft loss in these patients. Increased awareness among clinicians is imperative, promoting early diagnosis of APRT deficiency and pharmacotherapy initiation before kidney transplantation.

Topics: Adenine Phosphoribosyltransferase; Adolescent; Adult; Aged; Allopurinol; Enzyme Inhibitors; Europe; Febuxostat; Female; Graft Survival; Humans; India; Kidney Failure, Chronic; Kidney Transplantation; Male; Metabolism, Inborn Errors; Middle Aged; New South Wales; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; United States; Urolithiasis; Xanthine Oxidase; Young Adult

Topics: Adolescent; Allopurinol; Cerebral Palsy; Delayed Diagnosis; Exons; Gout Suppressants; Humans; Hypoxanthine Phosphoribosyltransferase; Kidney Failure, Chronic; Lesch-Nyhan Syndrome; Male; Radiography, Thoracic; Renal Dialysis; Scoliosis; Uric Acid

Topics: Allopurinol; Disease Progression; Gout Suppressants; Humans; Kidney Failure, Chronic

Hyperuricemia has been epidemiologically associated with multiple comorbidities including chronic renal failure and cardiovascular disease. Cause and effect are difficult to address, given comorbidities associated with and prevalence of metabolic syndrome. One impediment to achieving serum uric acid (sUa) levels less than or equal to 6.0 mg/DL is the concept that allopurinol might be nephrotoxic. We examined the relation of sUa less than or equal to 6.0 mg/dL to renal function over time.. This is a medical records review study of 348 hyperuricemia patients identified in 2015, as having been followed with serial uric acid measurements. After 1 year of serial urate levels, to allow for treatment, patient cohorts were defined: sUa less than or equal to 6.0 mg/dL and sUa greater than 6.0 mg/dL. A repeated measure model was used to test for an association between uric acid level and serum creatinine, while adjusting for covariates.. There was a significant difference in the least square means of serum creatinine comparing those who achieved an sUa less than or equal to 6.0 mg/dL versus sUa greater than 6.0 mg/dL (1.39 mg/dL [95% confidence interval, 1.30-1.48] vs 1.57 mg/dL [95% confidence interval, 1.46-1.69]; p = 0.0015). This is a between-group difference in creatinine of 0.18 mg/dL. If a change in serum creatinine of 0.2 is considered significant, this short-term between-group progression of renal failure approaches clinical significance.. Given that most serial measures were within the first few years of follow-up, and change in renal function occurs slowly over time, the between group difference of sUa of 0.18 mg/dL is close to a clinically significant creatinine difference of 0.2 mg/dL.

Topics: Aged; Allopurinol; Antimetabolites; Comorbidity; Correlation of Data; Creatinine; Disease Progression; Female; Humans; Hyperuricemia; Kidney Failure, Chronic; Kidney Function Tests; Male; Metabolic Syndrome; Outcome Assessment, Health Care; Prevalence; United States; Uric Acid

We report a case of calcium pyrophosphate dihydrate deposition disease (CPDD) involving a patient on maintenance hemodialysis (MHD). The 32-year-old man presented in August 2016 with a complaint of left shoulder swelling of 8 months' duration with no trauma or fever. He was diagnosed with nephrotic syndrome in 1998, which progressed to ESRD. He commenced MHD in 2012. Examination at our hospital revealed a soft nontender swelling of the left shoulder. Blood biochemistry showed elevated serum urate, phosphate, β2 microglobulin, and parathyroid hormone. Imaging revealed joint effusion and dense heterogenous deposition. Aspirate analysis showed urate crystals 3+, and culture yielded no growth. Following rheumatology review, the working diagnosis was periarticular tissue tuberculosis, after excluding pseudogout and amyloidosis. Following 1 month of colchicine and allopurinol, synovial fluid microscopy showed CPDD crystals. Symptoms gradually resolved over the course of 6 months. In this rare case, a diagnosis of CPDD was made with a multidisciplinary approach that included imaging and biochemical investigations.

Topics: Adult; Allopurinol; Bone Diseases, Metabolic; Chondrocalcinosis; Colchicine; Humans; Kidney Failure, Chronic; Male; Nephrotic Syndrome; Renal Dialysis; Vietnam

A lower serum uric acid (UA) level has been associated with a higher mortality rate in haemodialysis patients. We investigated the long-term confounding factors of UA and mortality, and fitted a marginal structural model (MSM) based on the causal effect of xanthine oxidoreductase inhibitors (XORi). In total, 2429 patients on regular dialysis from April 2013 to March 2016 were included, and divided into quintiles by serum UA with Kaplan Meier (KM) curves and log rank analysis. Baseline characteristics were evaluated for relationships with all-cause mortality and cardiovascular disease (CVD) using the Cox hazard model. The MSM was used to control for time-dependent confounders of the XORi treatment effect. KM curves indicated that patients in the highest UA quintile had better outcomes than those in the lowest UA quintile. UA was not correlated with all-cause mortality or CVD events in the Cox model; however, the hazard ratio (HR) for mortality was 0.96 for the baseline administration of XORi. The MSM analysis for the effect of XORi treatment on all-cause mortality revealed a HR of 0.24 (95% confidence interval: 0.15-0.38) in all cohorts. These results suggest that XORi improved all-cause mortality in end-stage renal disease, irrespective of the serum UA level.

Topics: Aged; Allopurinol; Cardiovascular Diseases; Enzyme Inhibitors; Febuxostat; Female; Gout Suppressants; Humans; Incidence; Kidney Failure, Chronic; Male; Models, Structural; Prognosis; Renal Dialysis; Risk Factors; Survival Rate; Uric Acid; Xanthine Dehydrogenase

To assess the effect of allopurinol dose/duration on the risk of renal failure in the elderly with allopurinol use.. We used the 5% random Medicare claims data from 2006 to 2012. Multivariable-adjusted Cox regression analyses assessed the association of allopurinol dose/duration with subsequent risk of developing incident renal failure or end-stage renal disease (ESRD) (no prior diagnosis in last 183 days) in allopurinol users, controlling for age, sex, race and Charlson-Romano comorbidity index. HRs with 95% CIs were calculated. Sensitivity analyses considered a longer baseline period (365 days), controlled for gout or used more specific codes.. Among the 30 022 allopurinol treatment episodes, 8314 incident renal failure episodes occurred. Compared with 1-199 mg/day, allopurinol dose of 200-299 mg/day (HR 0.81; 95% CI 0.75 to 0.87) and ≥300 mg/day, 0.71 (0.67 to 0.76), had significantly lower hazard of renal failure in multivariable-adjustment model, confirmed in multiple sensitivity analyses. Longer allopurinol use duration was significantly associated with lower hazards in sensitivity analyses (365-day look-back; reference, <0.5 year): 0.5-1 year, 1.00 (0.88, 1.15); >1-2 years, 0.85 (0.73 to 0.99); and >2 years, 0.81 (0.67 to 0.98). Allopurinol ≥300 mg/day was also associated with significantly lower risk of acute renal failure and ESRD with HR of 0.89 (0.83 to 0.94) and 0.57 (0.46 to 0.71), respectively.. Higher allopurinol dose is independently protective against incident renal failure in the elderly allopurinol users. A longer duration of allopurinol use may be associated with lower risk of incident renal failure. Potential mechanisms of these effects need to be examined.

Topics: Acute Kidney Injury; Administrative Claims, Healthcare; Aged; Aged, 80 and over; Allopurinol; Female; Gout; Gout Suppressants; Humans; Incidence; Kidney Failure, Chronic; Male; Medicare; Protective Factors; Retrospective Studies; Time Factors; United States

Adenine phosphoribosyltransferase deficiency is a rare autosomal recessive disorder of uric acid metabolism that leads to formation and excretion of 2,8-dihydroxyadenine into urine. The low solubility of 2,8-dihydroxyadenine results in precipitation and formation of urinary crystals and renal stones. Patients with this disorder usually have recurrent nephrolithiasis and can develop nephropathy secondary to crystal precipitation in the renal parenchyma. The disease is most often underdiagnosed and can recur in renal transplant, causing graft failure. Lack of specific clinical manifestations, chemical and radiologic features identical to those shown with uric acid stones, and lack of awareness among clinicians are among the causes for the underdiagnoses of this treatable disease. Allopurinol, a xanthine dehydrogenase inhibitor, is the mainstay of treatment, supported by high fluid intake and dietary modifications. The possibility of adenine phosphoribosyl transferase deficiency should be considered in all cases of urolithiasis in children, patients with recurrent urolithiasis, and patients with urolithiasis associated with renal failure of unknown cause, including patients with end-stage renal disease and renal transplant recipients. Here, we report a case of a 41-year-old female patient who had a late diagnosis of 2,8-dihydroxyadenine nephropathy-induced end-stage renal disease, made on the native nephrectomy that accompanied the renal transplant, and who had a timely intervention that prevented recurrence in the graft.

Topics: Adenine; Adenine Phosphoribosyltransferase; Adult; Allopurinol; Biomarkers; Biopsy; Enzyme Inhibitors; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Metabolism, Inborn Errors; Treatment Outcome; Urolithiasis; Xanthine Dehydrogenase

Hyperuricemia is common in chronic kidney disease (CKD), but data regarding the relationship between serum uric acid levels and the long-term outcomes of CKD patients have been limited. The present study evaluated the associations between baseline serum uric acid levels with mortality and end-stage renal disease (ESRD). The subjects of this study were 551 stage 2-4 CKD patients. Cox proportional hazards models were used to evaluate the relationship between serum uric acid tertiles and all-cause mortality, cardiovascular disease (CVD) mortality, 50 % reduction in estimated glomerular filtration rate (eGFR), and development of ESRD, initially without adjustment, and then after adjusting for several groups of covariates. The mean age of the study subjects was 58.5 years, 59.3 % were men, and 10.0 % had diabetes. The mean eGFR was 42.02 ± 18.52 ml/min/1.73 m(2). In all subjects, the mean serum uric acid level was 6.57 ± 1.35 mg/dl, and 52.2 % of study subjects were on hypouricemic therapy (allopurinol; 48.3 %) at baseline. Thirty-one patients (6.1 %) died during a follow-up period of approximately 6 years. There was no significant association between serum uric acid level and all-cause mortality, CVD mortality, development of ESRD and 50 % reduction in eGFR in the unadjusted Cox models. In the adjusted models, hyperuricemia was found to be associated with all-cause mortality and CVD mortality after adjustment with CVD risk factors, kidney disease factors, and allopurinol, but not associated with development of ESRD and 50 % reduction in eGFR. The results of this study showed that hyperuricemia but not serum uric acid levels were associated with all-cause mortality, CVD mortality after adjustments with CVD risk factors, kidney disease factors, and allopurinol in stage 2-4 CKD patients.

Topics: Aged; Allopurinol; Biomarkers; Cause of Death; Female; Glomerular Filtration Rate; Gout Suppressants; Humans; Hyperuricemia; Japan; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Odds Ratio; Proportional Hazards Models; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Uric Acid

Purine nucleotide liberation and their metabolic rate of interconversion may be important in the development of hypertension and its renal consequences. In the present study, blood triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) breakdown pathway was evaluated in relation to uric acid concentration and xanthine dehydrogenase/xanthine oxidase (XDH/XO) in patients with essential hypertension, patients with chronic renal diseases on dialysis, and control individuals. The pattern of nucleotide catabolism was significantly shifted toward catabolic compounds, including ADP, AMP, and uric acid in patients on dialysis program. A significant fall of ATP was more expressed in a group of patients on dialysis program, compared with the control value (p<0.001), while ADP and AMP were significantly increased in both groups of patients compared with control healthy individuals (p<0.001), together with their final degradation product, uric acid (p<0.001). The index of ATP/ADP and ATP/uric acid showed gradual significant fall in both the groups, compared with the control value (p<0.001), near five times in a group on dialysis. Total XOD was up-regulated significantly in a group with essential hypertension, more than in a group on dialysis. The activity of XO, which dominantly contributes reactive oxygen species (ROS) production, significantly increased in dialysis group, more than in a group with essential hypertension. In conclusion, the examination of the role of circulating purine nucleotides and uric acid in pathogenesis of hypertension and possible development of renal disease, together with XO role in ROS production, may help in modulating their liberation and ROS production in slowing progression from hypertension to renal failure.

Topics: Adenine Nucleotides; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Blood Pressure; Creatinine; Disease Progression; Essential Hypertension; Female; Humans; Hypertension; Kidney Failure, Chronic; Male; Renal Dialysis; Urea; Uric Acid; Xanthine Dehydrogenase; Xanthine Oxidase

Gouty arthritis is a metabolic disorder associated with hyperuricemia. Despite the development of novel pharmacotherapies, some hyperuricemia patients are drug refractory and develop gout. A 74-year-old man with frequent gouty attacks and chronic renal failure presented with asymmetrical polyarthritis affecting multiple joints. The diagnosis of gout was confirmed based on the presence of monosodium urate crystals in the patient's right wrist. The administration of systemic corticosteroids relieved the joint inflammation and pain; however, the urate level increased to 28 mg/dL and the gout attacks recurred. Combined allopurinol, febuxostat, and benzbromarone therapy reduced the urate level to <6 mg/dL, and the attacks gradually declined. This is the first report of two xanthine oxidase inhibitors being used to treat refractory gout.

Topics: Adrenal Cortex Hormones; Aged; Allopurinol; Arthritis, Gouty; Benzbromarone; Drug Therapy, Combination; Febuxostat; Gout Suppressants; Humans; Hyperuricemia; Kidney Failure, Chronic; Male; Thiazoles; Treatment Outcome; Xanthine Oxidase

A 41 year old patient started treatment with 300 mg/d allopurinol for asymptomatic hyperuricaemia (9,2 mg/dl).. 4 weeks later he developed exfoliative skin lesions with haemorrhage, fever, eosinophilia and acute liver and renal failure, typical for an allopurinol hypersensitivity syndrome (AHS).An orthotopic liver-transplantation was performed.. The AHS is a serious iatrogenic disease. 2 % of the treated patients develop a skin rash. 0,4 % of these patients experience suddenly and unforeseen a severe hypersensitivity with a mortality of 14-30 %. An early diagnosis is often very difficult. In the pathogenesis different causes are discussed. A hereditary component is involved. Of essential importance is the amount of the starting dose, the kidney function and concomitant drugs. In an asymptomatic hyperuricaemia the application of allopurinol is not indicated. If strong indications are present, the allopurinol therapy has to start with the lowest dose (100 mg/d). If required this dose should be increased under consequent supervision only.

Topics: Adult; Allopurinol; Amoxicillin; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Drug Hypersensitivity; Drug Interactions; Drug Therapy, Combination; Follow-Up Studies; Humans; Hyperuricemia; Kidney Failure, Chronic; Liver Transplantation; Male; Risk Factors; Scarlet Fever; Stevens-Johnson Syndrome

The role of xanthine oxidase (XOD) in patients undergoing chronic hemodialysis treatment (HD) is poorly understood. Geriatric nutritional risk index (GNRI) ≤ 90 could be linked with malnutrition-inflammation complex syndrome. This study measured XOD, myeloperoxidase (MPO), superoxide dismutase (SOD), lipid hydroperoxides, total free thiol groups, and advanced oxidation protein products (AOPP) in 50 HD patients before commencing (pre-HD) and immediately after completion of HD session (post-HD) and in 22 healthy controls. Pre-HD serum hydroperoxides, AOPP, XOD, and SOD were higher and total thiol groups were lower in patients than in controls (P < 0.05, resp.). Compared to baseline values, serum MPO activity was increased irrespective of GNRI status. Serum XOD activity was increasing during HD treatment in the group with GNRI ≤ 90 (P = 0.030) whilst decreasing in the group with GNRI > 90 (P = 0.002). In a multiple regression analysis, post-HD serum XOD activity was independently associated with GNRI ≤ 90 ( β ± SE: 0.398 ± 0.151; P = 0.012) and HD vintage ( β ± SE: -0.349 ± 0.139; P = 0.016). These results indicate that an upregulated XOD may be implicated in HD-induced oxidative injury contributing to accelerated protein damage in patients with GNRI ≤ 90.

Topics: Antioxidants; Biomarkers; Case-Control Studies; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Nutritional Status; Oxidative Stress; Peroxidase; Regression Analysis; Renal Dialysis; Superoxide Dismutase; Xanthine Oxidase

Topics: Adult; Allopurinol; Chromatography, High Pressure Liquid; Drug Overdose; Female; Gout; Gout Suppressants; Humans; Kidney Failure, Chronic; Oxypurinol; Ribonucleosides; Risk Factors; Transsexualism

Nicorandil exhibits a protective effect in the vascular system, which is thought to be due to vasodilatation from opening ATP-dependent potassium channels and donation of nitric oxide. Recently, nicorandil was shown to be renoprotective in models of acute kidney injury and glomerulonephritis. However, the specific mechanisms of renoprotection are unclear. We evaluated the effect of nicorandil on the rat remnant kidney model of chronic kidney disease. Blood pressure was unchanged by a 10-wk course of nicorandil, while albuminuria was significantly reduced. Glomerular injury and tubulointerstitial injury were also ameliorated by nicorandil. Oxidative stress, as noted by renal nitrotyrosine level and urine 8-hydroxy-2'-deoxyguanosine, were elevated in this model and was significantly reduced by nicorandil treatment. Treatment was associated with maintenance of the mitochondrial antioxidant, manganese SOD, in podocytes and with suppression of xanthine oxidase expression in infiltrating macrophages. Interestingly, these two cell types express sulfonylurea receptor 2 (SUR2), a binding site of nicorandil in the ATP-dependent K channel. Consistently, we found that stimulating SUR2 with nicorandil prevented angiotensin II-mediated upregulation of xanthine oxidase in the cultured macrophage, while xanthine oxidase expression was rather induced by blocking SUR2 with glibenclamide. In conclusion, nicorandil reduces albuminuria and ameliorates renal injury by blocking oxidative stress in chronic kidney disease.

Topics: Albuminuria; Animals; ATP-Binding Cassette Transporters; Blotting, Western; Cells, Cultured; Disease Progression; Immunohistochemistry; KATP Channels; Kidney; Kidney Failure, Chronic; Kidney Glomerulus; Macrophages; Male; Mice; Nephritis, Interstitial; Nicorandil; Nitric Oxide; Oxidative Stress; Paraffin Embedding; Potassium Channels, Inwardly Rectifying; Rats; Rats, Sprague-Dawley; Receptors, Drug; Sulfonylurea Receptors; Xanthine Oxidase

We report the case of a man with chronic tophaceous gout who had end-stage renal failure secondary to the Alport syndrome. Following a failed kidney transplant, where urate deposition was a suspected contributor, the patient responded positively to consistent allopurinol therapy and regular haemodialysis sessions. Extensive and destructive tophi receded in size remarkably and the almost constant incidence of acute attacks of gout subsided. The patient has recently received a new kidney transplant and his plasma concentrations of urate are controlled well with allopurinol and he no longer experiences acute attacks of gout. While efficacious, adherence is critical for achieving the therapeutic effects of allopurinol even in end-stage renal disease.

Topics: Allopurinol; Follow-Up Studies; Gout; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

The body metabolism of patients with end-stage renal disease may be altered in response to long-term dialysis treatment. Moreover, the pattern of serum metabolites could change depending on the type of dialysis modality used. However, dialysis modality-dependent changes in serum metabolites are poorly understood. Our aim was to profile comprehensively serum metabolites by exploiting a novel method of (1)H-NMR-based metabonomics and identify the differences in metabolite patterns in subjects receiving haemodialysis (HD) and peritoneal dialysis (PD).. Anuric and non-diabetic HD patients were matched to PD patients for age, sex and dialysis duration. Accurate concentrations of serum metabolites were determined using the target-profiling procedure, and differences in the levels of metabolites were compared using multivariate analysis.. Principal Components Analysis score plots showed that the metabolic patterns could be discriminated by dialysis modalities. Hypoxanthine and inosine were present only with HD, whereas serum xanthine oxidase activity and uric acid levels were not different. In contrast, PD was associated with higher levels of lactate, glucose, maltose, pyruvate, succinate, alanine, and glutamate linked to glucose metabolism and the tri-carboxylic acid cycle. Maltose appeared only in patients using icodextrin solution for PD. Known uraemic retention solutes such as urea, creatinine, myo-inositol and trimethylamine-N-oxide were increased in both dialysis groups.. Metabonomics shows apparent differences in the profiles of serum metabolites between HD and PD, which were influenced by dialysis-related processes. Inosine and hypoxanthine are present only in HD patients, which is likely to represent more hypoxic and oxidative stress.

Topics: Case-Control Studies; Creatinine; Female; Humans; Hypoxanthine; Inosine; Kidney Failure, Chronic; Magnetic Resonance Spectroscopy; Male; Metabolomics; Middle Aged; Peritoneal Dialysis; Principal Component Analysis; Renal Dialysis; Xanthine Oxidase

To study the prevalence of chronic kidney disease (CKD) and its impact on allopurinol dosing and uric acid control among patients with gout.. This was a retrospective study using data from a large US health plan. Claims and laboratory data were analyzed for enrollees from the health plan database from January 2002 through December 2005. Patients with gout were identified from pharmacy and medical claims data based on the presence of codes for gout medication or gout diagnosis. Severity of CKD was determined using the estimated glomerular filtration rate (eGFR). Allopurinol titration was defined as a change in average daily dose from first prescription to last prescription of ≥ 50 mg.. A total of 3,929 patients were identified for inclusion in this study, 39% of whom had CKD (based on having an eGFR < 90 mL/min/1.73 m2). Subjects with CKD were older (p < 0.01) and more likely to be women (p < 0.01), had a greater number of comorbid conditions (p < 0.01), and were more likely to be prescribed allopurinol (p < 0.01) compared to those with no CKD. The average starting dose of allopurinol was lower among those with CKD, and it decreased with worsening kidney function. Among the 3,122 gout patients who used allopurinol, only 25.6% without CKD and 22.2% with CKD achieved a serum uric acid concentration of < 6.0 mg/dL (p = 0.0409). Also, only 15% of allopurinol users had an upward dose titration (by ≥50 mg), but the average increase in dose did not differ significantly between those with and without CKD.. About two out of every five patients with gout in this population had CKD. Allopurinol doses were not adjusted in the majority of CKD patients. Serum uric acid control in gout was poor among patients without CKD and even worse among those with CKD.

Topics: Adult; Aged; Allopurinol; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Managed Care Programs; Middle Aged; Retrospective Studies; Uric Acid

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

Mutations in the UMOD gene encoding uromodulin (Tamm-Horsfall glycoprotein) result in the autosomal dominant transmission of progressive renal insufficiency and hypo-uricosuric hyperuricemia leading to gout at an early age. The clinical appearance is characterized by renal insufficiency and gout occurring in the late teenage years, with end-stage kidney disease characteristically developing between 40 and 70 years of age. This report provides a long-term characterization of renal functional decline in three children from one family with a novel UMOD mutation (c.891T>G, p.C297W) who received allopurinol and a low protein diet. While renal functional decline is slow in individuals with UMOD mutations, it may appear early in life and be associated with marked hyperuricemia. Anemia was also noted in this family.

Topics: Adult; Allopurinol; Anemia; Antimetabolites; Child; Child, Preschool; Combined Modality Therapy; Diet, Protein-Restricted; Family Health; Female; Genetic Predisposition to Disease; Glomerular Filtration Rate; Humans; Hyperuricemia; Infant; Kidney Failure, Chronic; Kidney Function Tests; Male; Mucoproteins; Mutation; Uromodulin

The present report describes the case of a 67-year-old patient who developed an allopurinol-induced hypersensitivity syndrome (AHS) with toxic epidermal necrolysis and subsequently died of septic multiorgan failure. Considering the increasing prescription rate of allopurinol, the present case report intends to demonstrate the underestimated threat of AHS.

Topics: Aged; Allopurinol; Diagnosis, Differential; Drug Hypersensitivity; Fatal Outcome; Gout; Humans; Kidney Failure, Chronic; Male; Multiple Organ Failure; Recurrence; Stevens-Johnson Syndrome

Topics: Allopurinol; Free Radical Scavengers; Humans; Kidney Failure, Chronic; Metabolic Syndrome; Oxidative Stress; Pilot Projects; Uric Acid

Acute tumor lysis syndrome (TLS) is a life-threatening complication of cancer therapy requiring prompt recognition and aggressive management. It occurs particularly in patients with lymphoproliferative disease during potent myelosuppressive therapy. To our knowledge, acute TLS in end-stage renal disease (ESRD) patients with malignancy is extremely rare and has never been reported in English literature. We report the first case of acute TLS in an ESRD woman with diffuse large B cell lymphoma after chemotherapy. Aggressive treatments with daily hemodialysis and allopurinol rather than hydration benefit the patient. There is neither optimal therapy in treating ESRD patients with TLS nor adequate guidelines for how to adjust the chemotherapy drug in hemodialysis patients. This case provides our experience to clinician how to treat acute TLS in ESRD patients.

Topics: Acute Disease; Allopurinol; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Blood Chemical Analysis; Cyclophosphamide; Dexamethasone; Enzyme Inhibitors; Female; Humans; Kidney Failure, Chronic; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Renal Dialysis; Tumor Lysis Syndrome; Vincristine

Aplastic anemia is a rare complication of allopurinol use. We report an unusual case of aplastic anemia associated with allopurinol therapy for hyperuricemia in a patient with chronic kidney disease. A 37-year-old female patient diagnosed with Stage III chronic kidney disease was admitted with pancytopenia. She had a history of taking allopurinol for 5 months. Her bone marrow showed extremely decreased cellularity (< 20%) and there was no malignant cell infiltration. She was free of infections, including parvovirus B19, cytomegalovirus and Epstein-Barr virus. These results suggested a diagnosis of aplastic anemia. Allopurinol was discontinued immediately and treatment with blood transfusions and prednisolone was begun. After 6 months, the bone marrow cellularity improved to approximately 70%. Recently, it was suggested that decreased activity of multidrug resistance P-glycoprotein may play a role in acquired aplastic anemia. So we measured the inhibitory effect of allopurinol and oxypurinol on P-glycoprotein activity. But neither allopurinol nor oxypurinol inhibited P-glycoprotein activity.

Topics: Adult; Allopurinol; Anemia, Aplastic; Enzyme Inhibitors; Female; Humans; Kidney Failure, Chronic

We report a case of Stevens-Johnson syndrome (SJS) caused by imatinib combined with allopurinol. An 82-year-old female patient who had a diagnosis of chronic myeloid leukemia was initially treated with imatinib 200 mg/day and allopurinol 100 mg for 42 days, and had a satisfactory hematological response. The dose of imatinib was adjusted to 400 mg/day for 14 days. After two weeks, she developed SJS and was transferred to the intensive care unit for further treatment because her general condition had deteriorated. The aggravated cutaneous adverse reaction improved approximately 7 days after withdrawal of imatinib. Oral steroids with antihistamines were prescribed for the treatment of severe cutaneous reaction. The symptoms of SJS completely improved 1 month after discontinuation of imatinib and allopurinol. We concluded that imatinib alone may cause serious cutaneous reaction, but the combination of 2 high-risk drugs may increase the likelihood of exposed patients developing SJS. Physicians should be aware of the possibility of SJS caused by imatinib and allopurinol prescribed simultaneously.

Topics: Aged, 80 and over; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Chronic Disease; Female; Humans; Imatinib Mesylate; Kidney Failure, Chronic; Leukemia, Myeloid; Piperazines; Pyrimidines; Stevens-Johnson Syndrome

Allopurinol was administered to end-stage renal disease (ESRD) patients with elevated uric acid levels presenting with symptoms of gout and also had risk factors of metabolic syndrome. The primary aim of this pilot study was to examine the effects of lowering uric acid levels using allopurinol on lipoprotein markers of metabolic syndrome in patients.. The study was conducted using a prospective open-label protocol. End-stage renal disease patients (n=12) (mean age: 45.8+/- 13.6 years) undergoing chronic hemodialysis were recruited through their treating physician to participate in this study. All patients had ESRD and were prescribed allopurinol (300 mg/bid) for gout over a 3-month period. Pre-allopurinol and post-allopurinol data was obtained on low-density lipoprotein (LDL) cholesterol, LDL particle number, LDL particle size, high-density lipoprotein (HDL) cholesterol, large HDL particle number, total cholesterol, triglycerides, large very-low density lipoprotein (VLDL) particle number, and uric acid. Changes in lipid values were measured using a one-sample exact Wilcoxon rank sum test.. Significant changes occurred in the primary outcome measures of serum uric acid levels (-3.53 mg/dL, p=0.01), LDL cholesterol (-14.00 mg/dL, p=0.04), and triglycerides (32.67 mg/dL, p=0.01). Trends were observed in lipid markers that warrant further investigation.. Novel findings of our study suggest that lowering uric acid in ESRD patients may help to reduce the risk of cardiovascular disease in this population. It should be noted than an increase in triglycerides may mitigate the reduction in risk.

Topics: Adult; Allopurinol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Female; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Metabolic Syndrome; Middle Aged; Pilot Projects; Renal Dialysis; Triglycerides; Uric Acid

Allopurinol-induced hypersensitivity syndrome is characterized by an idiosyncratic reaction involving multiple-organs, which usually begins 2 to 6 weeks after starting allopurinol. In rare cases, the adverse reactions to allopurinol are accompanied by a variety of liver injury, such as reactive hepatitis, granulomatous hepatitis, vanishing bile duct syndrome, or fulminant hepatic failure. Here we report a case with granulomatous hepatitis and ductopenia. A 69-year-old man with chronic renal failure, hyperuricemia, and previously normal liver function presented with jaundice, skin rash, and fever 2 weeks after taking allopurinol (200 mg/day). In histopathology, a liver biopsy specimen showed mild spotty necrosis of hepatocytes, marked cholestasis in parenchyma, and some granulomas in the portal area. There were vacuolar degeneration in the interlobular bile ducts and ductopenia in the portal tracts. Pathologic criteria strongly suggested the presence of allopurinol-induced granulomatous hepatitis with ductopenia and cholestasis. The patient fully recovered following the early administration of systemic corticosteroid therapy.

Topics: Aged; Allopurinol; Antimetabolites; Bile Duct Diseases; Bile Ducts, Intrahepatic; Chemical and Drug Induced Liver Injury; Cholestasis; Drug Eruptions; Granuloma; Humans; Kidney Failure, Chronic; Male

Gout continues to be a health problem around the world, and the treatment may turn into a real challenge when the patient presents a certain degree of chronic renal failure (CRF). We discuss a case of tophaceous gout in a 68-year-old male patient without urolithiasis and with uric acid (UA) underexcretion and CRF (creatinine clearance of 42 ml/min). Uricosuric treatment with benzbromarone and urinary alkalinization was administered, and acute gouty attacks improved substantially. Subsequently, allopurinol was added to the treatment to accelerate tophi reduction in the hands, feet, elbows and knees. After 30 months of treatment, serum UA declined from 10 to 3.2 mg/dl. Urinary UA excretion of 0.44 g/24 h in the baseline rose to 0.85 g/24 h, returning to the baseline value after 30 months. UA clearance tripled, rising from 3.05 ml/min before treatment to 9.48 ml/min, and remained at this level. It is worth stressing that even in cases of severe tophaceous gout, the response to clinical treatment may be satisfactory with substantial reduction of tophi and full acute gouty attack remission even in patients presenting a certain degree of CRF.

Topics: Aged; Allopurinol; Benzbromarone; Glomerular Filtration Rate; Gout; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Treatment Outcome; Uric Acid; Uricosuric Agents

Although mild hyperuricemia is common in patients with renal disease, it has usually been considered a marker of reduced nephron mass rather than a risk factor for progression of kidney disease. On the other hand, experiments in a rat model demonstrated important deleterious effects of mild hyperuricemia on several aspects of renal structure and function. In the present investigation, the impact of the discontinuation of allopurinol therapy on the control of hypertension and the rate of progression of chronic kidney disease was considered. The present work involved 50 patients, suffering from stage 3 and 4 chronic kidney disease. All of them were on chronic allopurinol therapy for the treatment of mild hyperuricemia. Their blood pressure, serum creatinine and uric acid levels were followed for 12 months following allopurinol withdrawal. Urinary transforming growth factor beta-1 (TGF-beta1) was assayed by a solid-phase enzyme-linked immunosorbent assay. After allopurinol withdrawal, significant worsening of hypertension, significant acceleration of the rate of loss of kidney function and a significant increase in the urinary excretion of TGF-beta1 were observed in the group of patients who were not receiving pharmacological blockers of the renin-angiotensin system. In conclusion, asymptomatic hyperuricemia has a deleterious effect on the progression of chronic kidney disease and the control of hypertension. This effect was blocked by treatment with renin-angiotensin system blockers.

Topics: Adult; Allopurinol; Antihypertensive Agents; Disease Progression; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypertension; Hyperuricemia; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Renin-Angiotensin System; Severity of Illness Index; Transforming Growth Factor beta1

Topics: Allopurinol; Gout; Hand Deformities, Acquired; Humans; Kidney Failure, Chronic; Male; Middle Aged

Patients with chronic renal disease have a very high mortality due to cardiovascular disease. However, the traditional risk factors are not the only one explanation. Nowadays, there are new risk factors becoming, and one of these is the oxidative stress. Besides today we know that when these patients receive haemodialysis are being exposed to an additional oxidative stress. The aim of this study was to measure and to compare the degree of oxidative stress in two groups of patients on different dialysis techniques: a) On-Line Haemodiafiltration three times / week (OL-HDF). b) Daily Om-Line haemodiafiltration ( six times / week ) ( dOL-HDF) We studied 9 patients with chronic renal disease stage 5 on hemodialysis. They all were men, with a medium age of 72,5 +/- 6 years. Five patients were on dOL-HDFand four on tOL-HDF. Glutathione (GSH) concentration of patients on dOL-HDF before dialysis was 742+/- 153 nmol/ml and post-dialysis de 878+/- 223. Blood GSSG concentration before and after dialysis was 34+/- 14 nmol/ml y 137+/- 74 nmol/ml (p< 0,03). GSSG/GSH ratio pre-dialysis was 58+/-10 and post-dialysis 169+/-65 ( p < 0,03). In OL-HDF group GSSG concentration and the ratio GSSG/GSH also increased in a significative way from 99+/-45 nmol/ml to 179+/-66 nmol/ml, and from 161+/- 99 to 337+/-143 ( p<0,05). We also found differences in pCR concentrations between both groups; 3+/-1,4 g/l in dOL-HDF and 8,75+/-5,8 g/l in HDF OL. (p< 0,05). We did not find differences between xatine-oxidase activity before and after hemodialysis and between groups. In conclusion, patient with terminal chronic renal disease on OL-HDF receive an additional load of oxidative stress, as the increase in GSSG/GSH ratio in both groups shows. However patients on dHDF-OL shows low ratios GSSG/GSH post-hemodialysis and low pCR concentrations, and maybe this could be explained because daily on line haemodiafiltration improves purification of inflammatory mediators. Clue words: Hemodialysis, oxidative stress, glutathione, gssg/gsh ratio, xantine oxidasa.

Topics: Adult; Aged; Aged, 80 and over; Glutathione Disulfide; Hemodiafiltration; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxidative Stress; Xanthine Oxidase

A 60-year-old man with diabetes mellitus and chronic renal insufficiency needing hemodialysis was admitted with a 3 months history of multiple hyperkeratotic papules on the trunk and extremities partly ulcerated with a keratotic central plug.. Laboratory tests revealed elevated levels of blood urea nitrogen, creatinine, and HbA (1c). Histopathology showed vertical strands of collagen perforating from the ulcerated lesions. COURSE, DIAGNOSIS AND TREATMENT: The biopsy specimen was consistent with acquired reactive perforating collagenosis. The progression was stopped and secondary wound healing was initiated after two weeks of therapy with allopurinol and PUVA.. Acquired reactive perforating collagenosis should be considered when ulcera with oystershell-like keratotic plugs are found especially in patients with predisposing diseases like diabetes and renal insufficiency. A good interdisciplinary cooperation between internist and dermatologist is crucial for the early recognition by histopathology and the immediate treatment.

Topics: Allopurinol; Antimetabolites; Blood Urea Nitrogen; Collagen Diseases; Creatinine; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Kidney Failure, Chronic; Male; Middle Aged; PUVA Therapy; Skin; Skin Diseases; Skin Ulcer; Treatment Outcome

Topics: Adult; Allopurinol; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Failure, Chronic

Although drug induced interstitial nephritis is a relatively common cause of renal failure,granulomatous forms remain a rare condition. The development of a chronic granulomatous interstitial nephritis due to allopurinol is exceptional, only three cases have been described previously. We report on a patient who presented a granulomatous interstitial nephritis after 10 years of allopurinol administration (300 mg/day). At diagnosis, he had end stage renal disease and dialysis treatment was needed. Two months after drug withdrawal and on corticoid treatment a slow recovery of renal function was observed, allowing the interruption of dialysis. Two years after, the creatinine clearance is 23 ml/min,being dialysis free. We discuss the differential diagnosis of granulomatous interstitial nephritis and its rare association with allopurinol treatment.

Topics: Adrenal Cortex Hormones; Aged; Allopurinol; Chronic Disease; Creatinine; Diagnosis, Differential; Granuloma; Humans; Hyperuricemia; Kidney Failure, Chronic; Male; Nephritis, Interstitial; Renal Dialysis; Sarcoidosis

Topics: Aged; Allopurinol; Epidermis; Fatal Outcome; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Necrosis; Stevens-Johnson Syndrome; Uric Acid

To report a rare case of combined hypersensitivity syndrome and pure red cell aplasia (PRCA) following allopurinol therapy.. A 43-year-old woman with underlying mesangioproliferative glomerulonephritis developed fever, generalized morbilliform rash, leukocytosis with marked eosinophilia, and hepatic dysfunction 3 weeks after starting allopurinol therapy (300 mg/day for 3 days followed by 200 mg/day) for hyperuricemia and arthritis. The clinical findings were judged to be a probable drug reaction according to the Naranjo probability scale. The drug-induced hypersensitivity syndrome (DHS) resolved after withdrawal of allopurinol and initiation of systemic corticosteroid therapy. However, there was progressive worsening of anemia with reticulocytopenia; PRCA was suspected. PRCA was judged to be a possible drug reaction according to the Naranjo probability scale. The patient refused blood transfusion and bone marrow biopsy. Recombinant human erythropoietin was initiated in addition to prednisolone 15 mg daily. Eleven days later (approximately 7 wk after allopurinol withdrawal), both the hemoglobin level and reticulocyte count began to rise. The patient consented to a bone marrow study at that time, which confirmed the presence of dysplasia involving only the erythroid lineage.. Allopurinol may induce DHS, aplastic anemia, and, in rare instances, PRCA. We report the first case of PRCA concurrent with allopurinol-induced DHS in a patient with chronic kidney disease. Discontinuation of allopurinol is the first step in the treatment of such cases. The slow recovery of PRCA might be partly attributed to her underlying chronic kidney disease.. To minimize serious DHS, proper indications for treatment and dosage adjustment should be closely observed when starting allopurinol therapy in patients with chronic kidney disease.

Topics: Adult; Allopurinol; Antimetabolites, Antineoplastic; Drug Eruptions; Drug Hypersensitivity; Female; Glomerulonephritis, Membranoproliferative; Humans; Hyperuricemia; Kidney Failure, Chronic; Red-Cell Aplasia, Pure

We report a patient with complete adenine phosphoribosyltransferase deficiency and urolithiasis, in whom 4 consecutive cadaveric renal transplantations were performed; 2,8-dihydroxyadenine crystal nephropathy recurred within weeks in the first and second graft when the patient was not treated with allopurinol immediately after transplantation. In the third graft, recurrence of disease could be prevented by immediate allopurinol treatment. This graft was lost due to chronic allograft nephropathy without significant crystal deposition. After a fourth transplantation, again without initial allopurinol, the disease recurred following an initial vascular rejection. Addition of allopurinol significantly improved renal function of the 2nd and 4th graft. This case indicates that outcome of renal transplantation in patients with adenine phosphoribosyltransferase deficiency critically depends on immediate postoperative pharmacotherapy with allopurinol, which is able to prevent 2,8-dihydroxyadenine nephropathy in the graft. Furthermore, rapid recurrence of disease without allopurinol seems to be triggered by delayed graft function and acute rejection.

Topics: Adenine Phosphoribosyltransferase; Adult; Allopurinol; Cadaver; Graft Rejection; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Postoperative Complications; Recurrence; Renal Dialysis; Urinary Calculi

Chronic renal failure (CRF) is associated with oxidative stress, the mechanism of which remains uncertain. Superoxide is the primary oxygen free radical produced in the body, NAD(P)H oxidase is the major source of superoxide production and superoxide dismutase (SOD) is responsible for removal of superoxide. We hypothesized that CRF-induced oxidative stress may be due to increased production and/or decreased dismutation of superoxide.. Immunodetectable superoxide dismutase isoforms (Cu Zn SOD and Mn SOD), as well as, NAD(P)H oxidase (gp91 phox subunit) proteins and xanthine oxidase (XO) activity were determined in the kidney and liver of CRF (5/6 nephrectomized) and sham-operated control rats. Subgroups of animals were treated with SOD-mimetic drug, tempol and blood pressure and urinary nitric oxide metabolites (NOx) were monitored.. The CRF group showed marked down-regulations of CuZn SOD and Mn SOD and significant up-regulation of gp91 phox in the liver and kidney, which are among the metabolically most active tissues. In contrast, XO activity was depressed in both tissues. Arterial pressure and nitrotyrosine abundance were elevated while urinary NOx excretion was depressed, pointing to increased NO inactivation by superoxide and decreased NO availability in CRF animals. Administration of SOD-mimetic agent, tempol, for one week, ameliorated hypertension, reduced nitrotyrosine abundance and increased urinary NOx excretion in the CRF animals.. CRF is associated with depressed SOD and elevated NAD(P)H oxidase expression, which can contribute to oxidative stress by increasing superoxide. This is evidenced by favorable response to administration of SOD-mimetic drug, tempol, and increased nitrotyrosine that is the footprint of NO interaction with superoxide.

Topics: Animals; Antioxidants; Cyclic N-Oxides; Down-Regulation; Hypertension, Renal; Kidney; Kidney Failure, Chronic; Male; Membrane Glycoproteins; NADPH Oxidase 2; NADPH Oxidases; Oxidative Stress; Rats; Rats, Sprague-Dawley; Spin Labels; Superoxide Dismutase; Up-Regulation; Xanthine Oxidase

Although hyperuricaemia and gout are frequently found in renal transplant recipients, little has been published on the efficacy of urate-lowering therapy (ULT) in this patient population. We therefore examine the effects of allopurinol and benziodarone therapy in a cohort of renal transplant patients.. We reviewed files from a cohort of 1328 patients that received renal transplantation. The selection criteria included: functioning allograft, hyperuricaemia for >12 months or gout, ULT lasting at least 1 year and at least two control measurements after the onset of ULT. Patients on azathioprine were treated with benziodarone to avoid azathioprine-allopurinol interactions.. Two-hundred and seventy-nine patients fulfilled the criteria for review. They were treated with 289 courses of ULT: 100 with allopurinol (mean dose: 376 mg/day/dl/min of creatinine clearance) and 189 with benziodarone (mean dose: 73 mg/day). The mean follow-up was 38 months. Both drugs were effective for the control of hyperuricaemia, but benziodarone caused greater reductions in serum uric acid levels, especially when used at mean doses of >75 mg/day. Severe side effects were uncommon, in both the allopurinol and benziodarone groups.. Both allopurinol and benziodarone were effective for the control of hyperuricaemia in renal transplantation. Benziodarone at doses >75 mg/day was more effective than allopurinol in reducing serum uric acid levels and also reduced the risk of azathioprine-allopurinol interactions.

Topics: Adolescent; Adult; Aged; Allopurinol; Antimetabolites; Azathioprine; Child; Cohort Studies; Female; Follow-Up Studies; Humans; Hyperuricemia; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Time Factors

Topics: Allopurinol; Colchicine; Coronary Disease; Gout; Gout Suppressants; Humans; Kidney Failure, Chronic; Patient Care Planning; Uric Acid

Topics: Aged; Aged, 80 and over; Allopurinol; Glucocorticoids; Gout; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Risk Factors; Time Factors; Uric Acid

A 73-year-old woman with chronic renal failure developed generalized muscular weakness and pain 6 days after the start of allopurinol treatment(200 mg/day). Routine laboratory tests revealed elevated levels of serum creatine kinase, and the patient was clinically diagnosed as rhabdomyolysis, due probably to severe myositis. A high level of serum oxipurinol, the chief active metabolite of allopurinol, was also revealed. The muscular weakness was relieved in seven weeks with intermittent hemodiafiltration.

Topics: Aged; Allopurinol; Female; Hemodiafiltration; Humans; Kidney Failure, Chronic; Myositis; Oxypurinol; Rhabdomyolysis

The amount of dehydroascorbic acid contained within total ascorbic acid (oxidized as well as non-oxidized forms) in plasma, hereafter referred to as the dehydroascorbic acid fraction, may be a measure of oxidative stress during haemodialysis. In the present study, we determined this fraction in chronic haemodialysis patients.. Using high performance liquid chromatography, dehydroascorbic acid and total ascorbic acid levels were measured in 80 maintenance haemodialysis patients for a period of > 2 years as well as in 49 controls, to examine a possible association of these compounds with clinical parameters and/or drugs taken by the patients.. Dialysis patients who had an increased plasma urate level (P < 0.05) and had been taking allopurinol (P < 0.05) or NSAID (non-steroid anti-inflammatory drugs) (P < 0.01), and dialysis patients who were younger (< or = 55 years), as compared with older dialysis patients (P < 0.01), were found to have a lower dehydroascorbic acid fraction by multivariate analysis. Mean plasma dehydroascorbic acid levels and dehydroascorbic acid fractions were significantly lower in the younger haemodialysis patients (4.8 +/- 0.7 micromol/l and 28.4 +/- 3.9%) than in healthy younger controls (13.3 +/- 1.1 micromol/l and 41.1 +/- 1.8%) (P < 0.0001 and P < 0.01, respectively). Moreover, a correlation was found between plasma dehydroascorbic acid fraction and plasma lipid peroxide (r = 0.66, P < 0.01) in patients who had not been taking allopurinol and/or NSAID.. We found that dehydroascorbic acid fraction was related to patients' age, plasma urate level and to taking allopurinol or NSAID. Dehydroascorbic acid fraction may be another indirect index of oxidative stress.

Topics: Aging; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Antimetabolites; Case-Control Studies; Dehydroascorbic Acid; Female; Humans; Kidney Failure, Chronic; Lipid Peroxides; Male; Middle Aged; Multivariate Analysis; Oxidative Stress; Reference Values; Renal Dialysis; Uric Acid

A 43-year-old man developed fever, skin rash, eosinophillia, and severe renal and liver dysfunction following treatment with allopurinol. The patient died after 3 months of hospitalization. Autopsy revealed systemic cytomegalovirus infection and bacteremia.

Topics: Adult; Allopurinol; Anti-Bacterial Agents; Antiviral Agents; Bacteremia; Cytomegalovirus Infections; Drug Hypersensitivity; Drug Therapy, Combination; Ganciclovir; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Skin; Skin Ulcer

We present a case of widespread reactive perforating collagenosis in a 63-year-old woman undergoing haemodialysis after diabetic nephropathy, who was treated successfully with allopurinol. The patient responded well and rapidly to a dose of 100 mg allopurinol daily. It is suggested that more patients with reactive perforating collagenosis may benefit from allopurinol therapy.

Topics: Allopurinol; Collagen Diseases; Diabetic Nephropathies; Female; Free Radical Scavengers; Humans; Kidney Failure, Chronic; Middle Aged; Renal Dialysis

Topics: Administration, Oral; Aged; Allopurinol; Chronic Disease; Desensitization, Immunologic; Drug Hypersensitivity; Female; Gout; Gout Suppressants; Heart Diseases; Humans; Kidney Failure, Chronic; Urea

To describe an allopurinol desensitization that failed on the first attempt but was successful on the second attempt, resulting in the management of crippling tophaceous gout.. A 64-year-old white man with a history of gouty nephropathy requiring hemodialysis developed a severe cutaneous reaction from exposure to allopurinol. The first desensitization attempt was unsuccessful, and the gouty nephropathy caused chronic cellulitus and urate microcrystal deposition on the patient's hands and feet. Continuous ambulatory peritoneal dialysis and hemodialysis were used to treat the patient's severe symptoms and increase uric acid clearance. This method, however, was ineffective. Severe tissue ischemia, requiring bilateral below-the-knee amputations, prompted the second desensitization attempt four years later. The second attempt, administered differently and with more caution, was successful and did not cause further complications.. Allopurinol is the only agent available to effectively reduce uric acid concentrations in those who are over-producers. Hypersensitivity-type reactions have been reported with its use, and desensitization is the only viable therapeutic option. Few cases of desensitization to allopurinol have been reported in the literature. This article describes a failure and a subsequent success in desensitization to allopurinol.. Although desensitization to allopurinol poses potential risks, the benefits can outweigh the risks of therapy. Desensitization requires close monitoring; if failure does occur, subsequent attempts can be successful, as this case report demonstrates.

Topics: Allopurinol; Desensitization, Immunologic; Drug Hypersensitivity; Gout; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

We studied purine metabolism in gouty patients from three categories: primary gout, familial juvenile hyperuricaemic nephropathy (FJHN) and partial HPRT deficiency.

Topics: Adolescent; Adult; Aged; Allopurinol; Benzbromarone; Creatinine; Drug Hypersensitivity; Gout; Gout Suppressants; Humans; Hypoxanthine Phosphoribosyltransferase; Kidney Failure, Chronic; Male; Middle Aged; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid

Topics: Adult; Allopurinol; Arthritis, Gouty; Combined Modality Therapy; Drug Resistance; Fatal Outcome; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Uric Acid

Topics: 5'-Nucleotidase; Adolescent; Adult; Aged; Allopurinol; Anemia, Hemolytic; Child; Child, Preschool; Consanguinity; Cytidine Diphosphate Choline; Erythrocytes; Female; Gout; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nuclear Family

Allopurinol is a xanthine oxidase inhibitor widely used to control plasma uric acid levels. Episodes of hypersensitivity to the drug are not rare. A severe form of this with a generalized exanthem, fever and liver involvement has been termed the allopurinol hypersensitivity syndrome (AHS). Patch testing and lymphocyte stimulation testing (LST) are not helpful in confirming this sensitivity. Allopurinol works as a substrate of xanthine oxidase, and is rapidly oxidized into oxypurinol in vivo. Therefore, the biological half-life of oxypurinol is markedly longer than that of allopurinol. In addition, conspicuous pre-existing renal impairment has been noted in many AHS patients. Thus, it is possible that AHS is a manifestation of hypersensitivity to oxy-, not allopurinol. Here, we now report three cases of AHS in which there were significant lymphoproliferative reactions to oxypurinol but not allopurinol.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Cystitis; Drug Hypersensitivity; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxypurinol; Xanthine Oxidase

In humans, adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency can manifest as nephrolithiasis, interstitial nephritis, and chronic renal failure. APRT catalyzes synthesis of AMP from adenine and 5-phosphoribosyl-1-pyrophosphate. In the absence of APRT, 2,8-dihydroxyadenine (DHA) is produced from adenine by xanthine dehydrogenase (XDH) and can precipitate in the renal interstitium, resulting in kidney disease. Treatment with allopurinol controls formation of DHA stones by inhibiting XDH activity. Kidney disease in APRT-deficient mice resembles that seen in humans. By age 12 wk, APRT-deficient male mice are, on average, mildly anemic and smaller than normal males. They have extensive renal interstitial damage (assessed by image analysis) and elevated blood urea nitrogen (BUN), and their creatinine clearance rates, which measure excretion of infused creatinine as an estimate of glomerular filtration rate (GFR), are about half that of wild-type males. APRT-deficient males treated with allopurinol in the drinking water had normal BUN and less extensive visible renal damage, but creatinine clearance remained low. Throughout their lifespans, homozygous null female mice manifested significantly less renal damage than homozygous null males of the same age. APRT-deficient females showed no significant impairment of GFR at age 12 wk. Consequences of APRT deficiency in male mice are more pronounced than in females, possibly due to differences in rates of adenine or DHA synthesis or to sex-determined responses of the kidneys.

Topics: Adenine Phosphoribosyltransferase; Aging; Allopurinol; Animals; Chimera; Creatinine; Disease Models, Animal; Female; Genotype; Glomerular Filtration Rate; Humans; Kidney; Kidney Calculi; Kidney Cortex; Kidney Failure, Chronic; Male; Mice; Mice, Inbred Strains; Mice, Knockout; Reference Values; Sex Characteristics

Topics: Aged; Allopurinol; Anemia; Captopril; Drug Interactions; Drug Resistance; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Piperidines; Recombinant Proteins

Possible mechanisms for the hypouricemic effects of the angiotensin II receptor antagonist losartan were examined using rats with experimental chronic renal failure (CRF) and control animals. The results show that losartan has a uricosuric effect in rats with normal or decreased renal function. Renal clearance of urate was increased 3-fold in CRF rats and 2-fold in control rats after 7 days of intraperitoneal losartan administration. Although the results show that losartan and its metabolite EXP-3174 alter urate and Cl- transport across isolated short-circuited intestine, these agents do not promote urate secretion into the intestinal lumen. Unidirectional urate and Cl- fluxes were reduced across normal rat colon and unaltered in the small intestine in the presence of losartan. In CRF rat colon, net secretion of urate and Cl- was abolished after losartan addition at 10(-5) M. Transport across the small intestine of CRF rats did not change in the presence of a similar concentration of drug. Losartan treatment of CRF rats before the removal of colonic tissues reversed the basal net secretion of urate to net absorption. These results suggest that the changes in intestinal transport observed in the presence of losartan appear to be mediated via the angiotensin II receptor antagonistic action of this drug. Direct determination of the effects of angiotensin II on urate and Cl- transport across colonic tissues from control animals revealed a significant angiotensin II stimulation of urate secretion. These angiotensin II-induced alterations in transport were inhibitable by losartan.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Biological Transport; Biphenyl Compounds; Chlorides; Colon; Homeostasis; Imidazoles; Intestinal Absorption; Kidney; Kidney Failure, Chronic; Losartan; Male; Rats; Rats, Sprague-Dawley; Sensitivity and Specificity; Tetrazoles; Urate Oxidase; Uric Acid; Xanthine Oxidase

The rise in plasma uric acid (UA) in chronic renal failure (CRF) is quite limited. This may be due to either increased extrarenal excretion, diminished biosynthesis, and/or enhanced degradation of uric acid. The intestinal flux studies revealed a striking modification of urate transport from no net flux to a net secretory flux in the jejunum and from a basal net absorptive to a net secretory flux in the colon of CRF animals. In addition, CRF animals showed a marked reduction in hepatic, renal, and enteric tissue xanthine oxidase activity and no significant change in tissue uricase activity. The correction of anemia with erythropoietin did not significantly alter the plasma concentration or urinary excretion of urate. Thus, enhanced enteric excretion and depressed production of uric acid (reduced xanthine oxidase activity) may account for the lack of significant hyperuricemia in CRF.

Topics: Animals; Erythropoietin; Intestinal Mucosa; Kidney; Kidney Failure, Chronic; Liver; Male; Nephrectomy; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Urate Oxidase; Uremia; Uric Acid; Xanthine Oxidase

Topics: Aged; Allopurinol; Drug Hypersensitivity; Fatal Outcome; Female; Gout; Humans; Kidney Failure, Chronic; Male; Middle Aged; Syndrome

Topics: Adenosine; Adult; Allopurinol; Amylases; Blood Glucose; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Duodenum; Glutathione; Histocompatibility Testing; Humans; Insulin; Kidney Failure, Chronic; Kidney Transplantation; Male; Organ Preservation; Organ Preservation Solutions; Pancreas Transplantation; Raffinose; Solutions; Spleen; Thrombosis; Tomography, X-Ray Computed; Transplantation, Homologous

Previous studies from these laboratories have demonstrated that uremic biologic fluids contain substances that suppress 1,25(OH)2D metabolism. Among these substances, it was found that uric acid suppresses 1 alpha-hydroxylase activity and synthesis of 1,25(OH)2D in rats. In this study, the effect of uric acid on plasma concentrations of 1,25(OH)2D in patients with renal failure was examined. Nine patients with stable chronic renal failure (serum creatinine, 1.9 to 6.4 mg/dL) were studied. None of the patients received vitamin D supplementation. Plasma concentrations of Ca, P, parathyroid hormone, creatinine, uric acid, 1,25(OH)2D, and 25(OH)D were measured before and 1 wk after the patients received allopurinol, 300 mg daily. Plasma creatinine, Ca, P, parathyroid hormone, and 25(OH)D did not change before or after allopurinol treatment. However, plasma uric acid decreased significantly from 7.3 +/- 0.4 to 4.0 +/- 0.4 mg/dL (P < 0.01) and plasma concentration of 1,25(OH)2D rose from 30.8 +/- 2.7 to 38.2 +/- 4.8 pg/mL (P < 0.01) after the ingestion of allopurinol. Allopurinol itself did not appear to directly enhance 1 alpha-hydroxylase activity in rats. It was concluded that a short-term administration of allopurinol suppresses plasmic uric acid and increases plasma 1,25(OH)2D in patients with chronic mild to moderate renal failure.

Topics: Adult; Aged; Allopurinol; Animals; Calcitriol; Calcium; DNA; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Rats; Receptors, Calcitriol; Uric Acid

The accumulation in blood plasma and efficiency of hemodialysis of pyrimidine compounds (orotic acid, orotidine, pseudouridine, uridine, thymine) as well as uric acid and creatinine in 23 patients with chronic renal failure (CRF) was investigated. As a reference, the analysis of the above metabolites in the plasma of 30 healthy volunteers was performed. Among examined compounds, pseudouridine possessed the highest capability of accumulation in blood plasma (25 times higher concentration than physiological). It coincided with the lowest efficiency of pseudouridine hemodialysis (44%) and the longest T1/2 (relative to creatinine) in plasma. A significant linear correlation (r = 0.81, p < 0.001) between efficiency of creatinine and pseudouridine hemodialysis was calculated. The concentration of orotic acid in the blood plasma of patients before hemodialysis exceeded 14 times its level in healthy subjects; the inhibition of uric acid synthesis by allopurinol in dialyzed patients was accompanied by enlargement of orotidine and orotate accumulation in blood plasma. Extremely high plasma concentration of examined pyrimidines remaining elevated after hemodialysis creates an additional hazard for tissue metabolism and health of patients with CRF.

Topics: Adult; Aged; Allopurinol; Creatinine; Female; Half-Life; Humans; Kidney Failure, Chronic; Male; Middle Aged; Orotic Acid; Pseudouridine; Pyrimidines; Renal Dialysis; Uric Acid; Uridine

Topics: Adult; Allopurinol; Bone Marrow Diseases; Gout; Humans; Kidney Failure, Chronic; Male

To determine the efficacy and safety of slow oral desensitization in the management of allopurinol-related pruritic cutaneous eruptions.. Nine patients with renal insufficiency and chronic tophaceous gouty arthritis, who had to interrupt their allopurinol therapy because of an allergic-type pruritic maculopapular eruption, were enrolled in an allopurinol oral desensitization protocol using a schedule of gradually increasing doses.. Cautious reinstitution of allopurinol was successfully accomplished in all nine patients, but four individuals required dose adjustment because of development of a mild, recurrent, macular rash early during the protocol at allopurinol doses of less than or equal to 5 mg/d. Transient, postdesensitization cutaneous reactions occurred in two patients, one of whom also had an early rash.. Oral desensitization to the minor rashes induced by allopurinol is a feasible and acceptably safe approach to therapy, particularly for those with renal insufficiency in whom no substitute urate-lowering drug is available.

Topics: Administration, Oral; Adolescent; Adult; Aged; Allopurinol; Chronic Disease; Desensitization, Immunologic; Drug Eruptions; Female; Gout; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pruritus

In an exploratory study the 24-h urinary excretion pattern of caffeine and 14 of its major metabolites was studied in 32 volunteers (adults, adolescents and children), 14 patients either with end stage renal disease or liver cirrhosis, 7 heavy smokers and 27 patients on therapy with cimetidine, allopurinol, theophylline or phenytoin. Caffeine and its metabolites were quantified by UV-absorption after liquid/liquid-extraction and HPLC-separation, which ensured proper analysis of 1-methyluric acid. In adults the renal excretion of caffeine derivatives corresponded to an intake of 509 mg caffeine/day, with 1-methyluric acid as the predominant metabolite. About 69% of caffeine was degraded by the paraxanthine pathway, and theobromine- (19%) and the theophylline pathway (14%) were less important. The ratio of paraxanthine formation to urinary caffeine concentration (= clearance equivalent) was about 2.2 ml.min-1.kg-1 in adults, and the corresponding ratios for theophylline and theobromine were 0.43 ml.min-1.kg-1 and 0.59 ml.min-1.kg-1, respectively. As expected, caffeine degradation was impaired in patients with cirrhosis and was increased in persons who smoked heavily or who were on phenytoin therapy. The results document the possibility of noninvasively investigating gross differences in caffeine disposition by analysis of the urinary pattern of its metabolites.

Topics: Adolescent; Adult; Age Factors; Allopurinol; Caffeine; Child; Cimetidine; Drug Interactions; Female; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Phenytoin; Smoking; Theophylline

Effects of hemodialysate of patients with chronic renal failure (CRF) on blastogenesis of human peripheral blood lymphocytes in the presence of concanavalin A or phytohemagglutinin was investigated. Hemodialysates from 11 CRF patients significantly promoted lymphocyte blastogenesis when compared with control dialysis fluids (p less than 0.01). The strongest activity (39% promotion of the lymphocyte blastogenesis) was observed with a hemodialysate obtained at 0.5 h after beginning dialysis. The activity decreased thereafter. On the contrary, the blastogenesis-promoting activity in plasma decreased significantly after hemodialysis (p less than 0.01, n = 11). To further confirm the presence of low-molecular-weight factor(s) in CRF, ultrafiltration of plasma obtained from CRF and healthy subjects was conducted using a membrane filter with a molecular cutoff of 3,000 D. The filtrate of CRF plasma significantly promoted lymphocyte blastogenesis when compared to that of healthy subjects (p less than 0.01). Heat treatment (100 degrees C, 40 min) did not abolish the activity of the hemodialysate. None of the drugs taken by the patients nor creatinine accumulated in CRF promoted the lymphocyte blastogenesis. Chromatographic analysis of a hemodialysate demonstrated several peaks which were absent in the control dialysis fluid. These results showed the presence of a novel lymphocyte-stimulating factor(s) in CRF, which is heat stable and has a low molecular weight (less than 3,000 D).

Topics: Allopurinol; Anabolic Agents; Androstanols; Calcitriol; Cells, Cultured; Concanavalin A; Creatinine; DNA Replication; Female; Furosemide; Humans; Kidney Failure, Chronic; Lectins; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Nifedipine; Reference Values; Renal Dialysis; Thymidine; Time Factors

Topics: Allopurinol; Humans; Hypoxanthine; Hypoxanthines; Kidney Failure, Chronic; Purine Nucleotides; Renal Dialysis; Uremia; Uric Acid; Xanthine; Xanthines

1. A compound identified as orotidine has been found in the erythrocytes of all subjects on allopurinol. 2. The erythrocyte orotidine concentrations were much higher in patients with renal failure or with the Lesch-Nyhan syndrome. 3. In addition, increased amounts of oxypurinol-7-riboside were excreted in the urine by both of these groups compared with control subjects or with patients with normal renal function on allopurinol. 4. A good correlation was found between urinary oxypurinol-7-riboside excretion and erythrocyte orotidine concentrations. 5. Increased erythrocyte levels of the pyrimidine-sugar UDP-glucose were also found in patients with the highest orotidine levels. 6. The combined results suggest a derangement of pyrimidine nucleotide metabolism during allopurinol therapy. We propose that erythrocyte orotidine formation results primarily from inhibition of orotidine-5'-monophosphate decarboxylase by oxypurinol-7-ribotide.

Topics: Allopurinol; Erythrocytes; Female; Humans; Kidney Failure, Chronic; Lesch-Nyhan Syndrome; Male; Nucleotides; Oxypurinol; Ribonucleosides; Uridine

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

A 43 year old female patient with chronic renal failure originated from polycystic kidney disease was admitted with pancytopenia. Prior to the admission, she had a history of taking allopurinol for 3 months. Allopurinol was discontinued immediately and she was treated with blood transfusion (platelet and RBC) and fluoxymesterone. The lymphocyte stimulation tests were negative for allopurinol and oxipurinol. The determination of serum levels of allopurinol and oxipurinol was disclosed to be not so high compared with other patients treated with allopurinol. On 45th day after admission, she was transfused with bone marrow from her elder brother. Thereafter bone marrow finding of the patient began to improve despite the lack of bone marrow engraftment. For further improvement, pulse treatment with corticosteroid was carried out. Although the pathophysiology of allopurinol-induced aplastic anemia remains unknown, it is interesting to note that bone marrow transfusion and pulse treatment with corticosteroid seemed effective in this case.

Topics: Adult; Allopurinol; Anemia, Aplastic; Blood Transfusion; Bone Marrow Transplantation; Female; Humans; Kidney Failure, Chronic; Methylprednisolone; Polycystic Kidney Diseases

A rare case of aplastic anemia which was considered to be induced by allopurinol was reported. A 48-year-old female had suffered from urolithiasis and chronic renal insufficiency. She was administered allopurinol for hyperuricemia for 4 months, and subsequently developed severe pancytopenia and bone marrow suppression. After stopping of allopurinol administration, she was administered prednisolone but died of gastro-intestinal tract bleeding and sepsis on the 21th hospital day, without hematological recovery.

Topics: Allopurinol; Anemia, Aplastic; Female; Humans; Kidney Failure, Chronic; Middle Aged; Uric Acid

Topics: Aged; Allopurinol; Anemia, Aplastic; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged

Monitoring of plasma oxypurinol has been proposed to prevent allopurinol side effects. An 89-year-old man developed a severe desquamative rash, fever, eosinophilia, hepatocellular injury and renal failure after allopurinol administration. Eight hours after the last dose, plasma allopurinol was undetectable and plasma oxypurinol was 50 mumol/l. This is the first case in which severe allopurinol hypersensitivity occurred despite a simultaneous plasma oxypurinol concentration within recommended levels (below 100 mumol/l).

Topics: Aged; Aged, 80 and over; Allopurinol; Chemical and Drug Induced Liver Injury; Dermatitis, Exfoliative; Drug Eruptions; Drug Hypersensitivity; Humans; Kidney Failure, Chronic; Male; Oxypurinol; Pyrimidines

Six days after initiating therapy with allopurinol, toxic epidermal necrolysis developed in a 73-year-old man with renal failure. It was responsible for a generalized vasculitis and gastrointestinal bleeding ultimately leading to death. The authors emphasize the need for a careful evaluation before prescribing this medication, particularly in patients with renal failure.

Topics: Aged; Allopurinol; Epidermolysis Bullosa; Gastrointestinal Hemorrhage; Humans; Kidney Failure, Chronic; Male; Uric Acid; Vasculitis

Topics: Allopurinol; Drug Hypersensitivity; Gout; Humans; Kidney Failure, Chronic; Kidney Glomerulus; Male; Middle Aged; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Aged; Allopurinol; Drug Eruptions; Humans; Kidney Failure, Chronic; Male

We report on a female patient with analgetic nephropathy in whom allopurinol therapy was started because of asymptomatic hyperuricemia and who 2 months later developed a syndrome characterized by icteric hepatitis, exfoliative dermatitis and progressive renal failure. After discontinuation of allopurinol and temporary peritoneal dialysis the patient recovered from the initially threatening condition. Analysis of case reports from the literature indicates that this syndrome is due to the allopurinol metabolite oxypurinol and is most frequently observed in patients with renal failure on concomitant treatment with diuretics.

Topics: Acute Kidney Injury; Aged; Allopurinol; Chemical and Drug Induced Liver Injury; Dermatitis, Exfoliative; Female; Humans; Kidney Failure, Chronic; Uric Acid

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

Topics: Acute Kidney Injury; Allopurinol; Chromatography, High Pressure Liquid; Female; Gout; Humans; Hypoxanthine Phosphoribosyltransferase; Kidney Failure, Chronic; Male; Oxypurinol

This paper illustrates several important points relating to the use of allopurinol in renal failure, or situations of purine overproduction: It is very easy to give too much allopurinol. Most of the side effects (bone marrow depression, exfoliative dermatitis, etc) are the result of overdosage due to the retention of oxipurinol, an effect exaggerated by thiazide diuretics. Monitoring of plasma oxipurinol levels (ideally less than 100 mumol/l) by high-pressure liquid chromatography is helpful for adjusting dosage in renal failure. Some estimate of the anticipated purine excess is equally vital in deciding dosage during tumour lysis if the risk of urate nephropathy is not to be substituted for the certainty of xanthine nephropathy. In this situation the use of allopurinol may even be questioned. Patients with HGPRT deficiency are exquisitely sensitive to allopurinol, and careful monitoring of the effect on urinary purine levels is essential if xanthine colic is to be avoided.

Topics: Adult; Allopurinol; Child; Child, Preschool; Creatinine; Female; Humans; Infant; Kidney Failure, Chronic; Male; Middle Aged; Monitoring, Physiologic; Oxypurinol; Purines; Uric Acid

Topics: Allopurinol; Drug Hypersensitivity; Female; Humans; Kidney Failure, Chronic; Middle Aged

Topics: Adult; Allopurinol; Anemia, Aplastic; Humans; Kidney Failure, Chronic; Male

Topics: Aged; Allopurinol; Captopril; Drug Synergism; Humans; Kidney Failure, Chronic; Male; Proline; Stevens-Johnson Syndrome

This report concerns a three month old infant who was failing to thrive. Renal insufficiency was demonstrated and attributed to aortic coarctation. However, surgical correction of the coarctation failed to correct the renal insufficiency completely and disproportionate hyperuricemia was noted. Excessive urinary excretion of uric acid was found and a moderate deficiency (6% of normal) of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) was demonstrated. When the urate over-production was corrected with allopurinol, renal function returned to normal and the child became well. The importance of over-production of urate and the resultant excessive urinary excretion of uric acid as a treatable cause of acute or persistent renal insufficiency is stressed.

Topics: Allopurinol; Aortic Coarctation; Humans; Hypoxanthine Phosphoribosyltransferase; Infant; Kidney Failure, Chronic; Male; Uric Acid

Topics: Adult; Aged; Allopurinol; Benzbromarone; Benzofurans; Drug Interactions; Drug Therapy, Combination; Gout; Humans; Kidney Failure, Chronic; Male; Middle Aged; Phenylbutazone

Topics: Adolescent; Adult; Aged; Allopurinol; Drug Hypersensitivity; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Orchitis; Vasculitis

In a series of 264 inpatients with nephrolithiasis and chronic renal insufficiency, 159 received follow-up care between 1 and 14 years (4.3 years on the average) after primary hospitalization. 59 of these 159 patients had to undergo nephrectomy in the course of calculus disease. Follow-up examinations showed no deterioration in 60 patients and a further 64 showed clear symptoms of improved renal function. In 23 patients renal function deteriorated and 11 of them had to be accepted in chronic dialysis. Special emphasis is placed on the relevance of thorough metaprophylaxis after calculus removal. Stone analyses of patients with renal insufficiency showed a high share of infectious stones (struvite and carbonic apatite) as well as of uric acid calculi. For that reason especially these patients require an intensive follow-up treatment.

Topics: Adolescent; Adult; Aged; Allopurinol; Anti-Bacterial Agents; Child; Citrates; Female; Follow-Up Studies; Humans; Kidney; Kidney Calculi; Kidney Failure, Chronic; Male; Middle Aged; Nephrectomy; Renal Dialysis

A four-year-old girl presented in renal failure due to dihydroxyadenine urolithiasis. Prior to this she had been fed a high purine macrobiotic diet, rich in pulses and grain. She was comatose, anuric, requiring peritoneal dialysis, and bilateral radiolucent renal calculi were revealed by ultrasonography and retrograde pyelography. 2,8-dihydroxyadenine stones were found at pyelolithotomy, renal biopsy revealed interstitial birefringent crystals, and a complete lack of adenine phosphoribosyl transferase (APRT) was found subsequently in erythrocyte lysates. APRT levels were initially falsely raised due to a blood transfusion on admission. The mother was shown to have heterozygote levels. The child was treated successfully with allopurinol, and a reduction in dietary purine but with only partial return of renal function.

Topics: Adenine; Adenine Phosphoribosyltransferase; Allopurinol; Child, Preschool; Diet, Vegetarian; Erythrocytes; Female; Humans; Kidney Calculi; Kidney Failure, Chronic

Topics: Amidophosphoribosyltransferase; Diet; Gout; Humans; Hypoxanthine Phosphoribosyltransferase; Kidney; Kidney Failure, Chronic; Metabolic Diseases; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Allopurinol; Humans; Kidney; Kidney Failure, Chronic; Oxypurinol; Renal Dialysis; Uric Acid

A patient with intractable tophaceous gout and advanced renal failure responded favorably to treatment by long-term hemodialysis and administration of allopurinol. Plasma uric acid levels returned to normal, tophi decreased in size, and the frequency of attacks of gout decreased markedly and permitted the patient to return to full-time employment.

Topics: Allopurinol; Gout; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Time Factors; Uric Acid

Five patients developed fever, "toxaemia", severe skin reactions and eosinophilia, three to six weeks after commencing allopurinol therapy. The presenting feature in these patients was an extensive erythema, progressing to an exfoliative dermatitis, sometimes with oral mucous membrane involvement. One patient developed toxic epidermal necrolysis. The clinical course in two patients was complicated by acute renal failure which necessitated dialysis. The clinical and laboratory features support an acute hypersensitivity mechanism in these allopurinol associated reactions, in agreement with previous studies. Patients with chronic renal failure appear particularly prone to severe, potentially fatal reactions. If these patients need allopurinol, a lower dose than would be normally required should be given.

Topics: Acute Kidney Injury; Adult; Allopurinol; Drug Eruptions; Drug Hypersensitivity; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Stevens-Johnson Syndrome

Topics: Allopurinol; Biotransformation; Clofibrate; Dose-Response Relationship, Drug; Humans; Kidney Failure, Chronic; Meperidine; Procainamide; Sulfonamides

De novo purine biosynthesis has been investigated in circulating blood lymphocytes in vitro. N-formyl-glycinamide ribonucleotide (FGAR) has been mesured using 14C-formate incorporation in the presence of azaserine, a metabolic inhibitor blocking the metabolical pathway at the level of FGAR synthesis. Such a synthesis was measured in 20 healthy controls, 24 patients with primary gout (11 on allopurinol therapy) and 26 patients with chronic renal failure and secondary hyperuricemia (8 on allopurinol therapy). Among gouty patients without allopurinol therapy, FGAR synthesis was normal in 5 and increased in the others. FGAR synthesis was decreased in patients with renal failure whatever the therapy. However, FGAR synthesis remained increased in patients with a primary gout complicated with renal insufficiency. The test we propose for de novo purine biosynthesis measurement is simple and of value to analyse the patho-physiology of hyperuricemia and its therapy. The test allows an acurate discrimination between primary and secondary hyperuricemia in the presence of renal insufficiency.

Topics: Adult; Allopurinol; Azaserine; Carbon Radioisotopes; Female; Formates; Gout; Humans; In Vitro Techniques; Kidney Failure, Chronic; Male; Metabolic Diseases; Methods; Middle Aged; Purines; Ribonucleotides; Uric Acid

Topics: Adult; Allopurinol; Anemia, Aplastic; Azathioprine; Blood Transfusion; Drug Interactions; Humans; Kidney Failure, Chronic; Kidney Transplantation; Leukemia, Myeloid; Leukocytes; Male; Transplantation, Homologous

Topics: Allopurinol; Desensitization, Immunologic; Drug Hypersensitivity; Gout; Humans; Kidney Failure, Chronic; Male; Middle Aged

Serum xanthine oxidase activity was measured by a radiochemical method in 137 consecutive patients with jaundice of varying etiology and in 40 non-jaundiced patients with liver or other disease. Serum xanthine oxidase was markedly increased, up to 50 times the upper normal limit (mean + 2 S.D.), in 32 out of 34 patients with infectious hepatitis. A slight elevation of serum xanthine oxidase, up to twice the upper normal limit, was found in 2 out of 49 patients with extrahepatic obstructive jaundice and in 4 out of 20 patients with chronic renal failure. In comparison to serum glutamic-oxaloacetic transaminase and lactate dehydrogenase serum xanthine oxidase appeared to be the more sensitive and specific indicator of acute hepatocellular damage.

Topics: Aspartate Aminotransferases; Chronic Disease; Hepatitis A; Humans; Jaundice; Kidney Failure, Chronic; L-Lactate Dehydrogenase; Liver Cirrhosis; Liver Neoplasms; Myocardial Infarction; Neoplasm Metastasis; Xanthine Oxidase

Topics: Alkylation; Allopurinol; Blood Proteins; Carbon Isotopes; Cyclophosphamide; Feces; Half-Life; Humans; Kidney Failure, Chronic; Liver Neoplasms; Neoplasms; Nitrobenzenes; Prednisolone; Protein Binding; Pyridines; Time Factors; Ultrafiltration

Topics: Adolescent; Adult; Allopurinol; Female; Humans; Kidney Failure, Chronic; Liver; Male; Middle Aged; Uric Acid

Topics: Adult; Allopurinol; Gout; Humans; Kidney Failure, Chronic; Male; Pyelonephritis

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: Adult; Allopurinol; Analysis of Variance; Benzofurans; Drug Combinations; Female; Humans; Kidney Failure, Chronic; Kidney Function Tests; Liver Function Tests; Male; Middle Aged; Uric Acid; Uricosuric Agents

Topics: Absorption; Adult; Allopurinol; Biological Transport; Chronic Disease; Glomerular Filtration Rate; Humans; Inulin; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Tubules; Middle Aged; Pyrazinamide; Uremia; Uric Acid; Uricosuric Agents

Topics: Adult; Aged; Allopurinol; Colchicine; Drug Synergism; Female; Gout; Humans; Kidney Calculi; Kidney Failure, Chronic; Male; Middle Aged; Phenylbutazone; Pyrazoles; Pyrimidines; Sulfhydryl Compounds; Uric Acid

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: Benzofurans; Humans; Kidney Failure, Chronic; Uric Acid; Uricosuric Agents; Vasodilator Agents; Xanthine Oxidase

Topics: Adolescent; Adult; Allopurinol; Electromyography; Fatigue; Female; Humans; Kidney; Kidney Failure, Chronic; Knee; Male; Median Nerve; Methods; Middle Aged; Muscle Contraction; Muscle Denervation; Muscles; Muscular Atrophy; Muscular Diseases; Neural Conduction; Neurologic Manifestations; Tracheotomy; Uremia

Topics: Allopurinol; Gout; Humans; Kidney Failure, Chronic; Uric Acid; Uricosuric Agents

Topics: Adult; Allopurinol; Child; Diabetes Mellitus; Female; Glycogen Storage Disease; Gout; Humans; Hypertension; Kidney Failure, Chronic; Male; Myxedema; Nutritional Physiological Phenomena; Pre-Eclampsia; Pregnancy; Psoriasis; Purines; Uric Acid; Uricosuric Agents

Topics: Adult; Aged; Allopurinol; Female; Gastrointestinal Diseases; Gout; Humans; Kidney Failure, Chronic; Male; Middle Aged; Skin Diseases; Uric Acid

Topics: Acidosis, Renal Tubular; Alcohol Oxidoreductases; Allopurinol; Biopsy; Blood Urea Nitrogen; Calcium Metabolism Disorders; Disulfiram; Enzyme Repression; Glyoxylates; Humans; Kidney; Kidney Calculi; Kidney Failure, Chronic; Leukocytes; Nephrocalcinosis; Oxalates; Pyridoxine

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: Adult; Aged; Allopurinol; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nitrogen; Uric Acid

Topics: Adult; Aged; Allopurinol; Female; Gout; Humans; Kidney Failure, Chronic; Male; Middle Aged; Xanthine Oxidase

Topics: Adult; Aged; Allopurinol; Female; Gout; Humans; Hypoxanthines; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Uric Acid; Xanthines

Topics: Allopurinol; Clopamide; Enzyme Therapy; Gout; Hematologic Diseases; Humans; Hypertension; Kidney Failure, Chronic; Polythiazide; Uric Acid; Xanthine Oxidase

Topics: Adolescent; Adult; Aged; Allopurinol; Child; Creatine; Enzyme Therapy; Female; Gout; Humans; Hydrogen-Ion Concentration; Hypoxanthines; Kidney Calculi; Kidney Failure, Chronic; Male; Middle Aged; Uric Acid; Xanthine Oxidase; Xanthines

Topics: Adult; Allopurinol; Calcium; Creatine; Enzyme Therapy; Gout; Humans; Kidney Failure, Chronic; Male; Middle Aged; Probenecid; Uric Acid; Xanthine Oxidase