allopurinol and Renal-Insufficiency

Topics: Allopurinol; Disease Progression; Humans; Renal Insufficiency; Renal Insufficiency, Chronic; Stroke

Gout is the most common inflammatory arthritis in men and is increasingly prevalent. Allopurinol is very effective at reducing plasma urate concentrations to a level sufficient to dissolve monosodium urate crystals. However, many patients fail to achieve a sufficient therapeutic response to allopurinol. Areas covered: This review covers the metabolism and pharmacokinetics of allopurinol and its active metabolite, oxypurinol and how these factors affect the plasma concentrations of urate at initiation and during long-term therapy with allopurinol. Significant aspects discussed are the importance of adherence to allopurinol therapy, allopurinol hypersensitivity reactions and insights into hyperuricemia. Expert opinion: The initial dosage of allopurinol should be low, particularly in patients with renal impairment. The dose should then be increased slowly until plasma concentrations of urate are sufficient to dissolve monosodium urate crystals (≤ 0.36 mmol/L). For this target, the maintenance dose of allopurinol can be estimated from the equation: Dose = 1413*(U

Topics: Allopurinol; Dose-Response Relationship, Drug; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Medication Adherence; Renal Insufficiency; Treatment Outcome; Uric Acid

Tumour lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Previous reviews did not find clear evidence of benefit of urate oxidase in children with cancer. This review is the second update of a previously published Cochrane review.. To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies.. In March 2016 we searched CENTRAL, MEDLINE, Embase, and CINAHL. In addition, we searched the reference lists of all identified relevant papers, trials registers and other databases. We also screened conference proceedings and we contacted experts in the field and the manufacturer of rasburicase, Sanofi-aventis.. Randomised controlled trials (RCT) and controlled clinical trials (CCT) of urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy.. Two review authors independently extracted trial data and assessed individual trial quality. We used risk ratios (RR) for dichotomous data and mean difference (MD) for continuous data.. We included seven trials, involving 471 participants in the treatment groups and 603 participants in the control groups. No new studies were identified in the update. One RCT and five CCTs compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase for the prevention of TLS.The RCT did not evaluate the primary outcome (incidence of clinical TLS). It showed no clear evidence of a difference in mortality (both all-cause mortality (Fisher's exact test P = 0.23) and mortality due to TLS (no deaths in either group)), renal failure (Fisher's exact test P = 0.46), and adverse effects between the treatment and the control groups (Fisher's exact test P = 1.0). The frequency of normalisation of uric acid at four hours (10 out of 10 participants in the treatment group versus zero out of nine participants in the control group, Fisher's exact test P < 0.001) and area under the curve of uric acid at four days (MD -201.00 mg/dLhr, 95% CI -258.05 mg/dLhr to -143.95 mg/dLhr; P < 0.00001) were significantly better in the treatment group.One CCT evaluated the primary outcome; no clear evidence of a difference was identified between the treatment and the control groups (RR 0.77, 95% CI 0.44 to 1.33; P = 0.34). Pooled results of three CCTs showed significantly lower mortality due to TLS in the treatment group (RR 0.05, 95% CI 0.00 to 0.89; P = 0.04); no clear evidence of a difference in all-cause mortality was identified between the groups (RR 0.19, 95% CI 0.01 to 3.42; P = 0.26). Pooled results from five CCTs showed significantly lower incidence of renal failure in the treatment group (RR 0.26, 95% CI 0.08 to 0.89; P = 0.03). Results of CCTs also showed significantly lower uric acid in the treatment group at two days (three CCTs: MD -3.80 mg/dL, 95% CI -7.37 mg/dL to -0.24 mg/dL; P = 0.04), three days (two CCTs: MD -3.13 mg/dL, 95% CI -6.12 mg/dL to -0.14 mg/dL; P = 0.04), four days (two CCTs: MD -4.60 mg/dL, 95% CI -6.39 mg/dL to -2.81 mg/dL; P < 0.00001), and seven days (one CCT: MD -1.74 mg/dL, 95% CI -3.01 mg/dL to -0.47 mg/dL; P = 0.007) after therapy, but not one day (three CCTs: MD -3.00 mg/dL, 95% CI -7.61 mg/dL to 1.60 mg/dL; P = 0.2), five days (one CCT: MD -1.02 mg/dL, 95% CI -2.24 mg/dL to 0.20 mg/dL; P = 0.1), and 12 days (one CCT: MD -0.80 mg/dL, 95% CI -2.51 mg/dL to 0.91 mg/dL; P = 0.36) after therapy. Pooled results from three CCTs showed higher frequency of adverse effects in participants who received urate oxi. Although urate oxidase might be effective in reducing serum uric acid, it is unclear whether it reduces clinical TLS, renal failure, or mortality. Adverse effects might be more common for urate oxidase compared with allopurinol. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing mortality or renal failure from TLS against the potential risk of adverse effects.

Topics: Adolescent; Allopurinol; Antimetabolites; Area Under Curve; Child; Controlled Clinical Trials as Topic; Humans; Neoplasms; Randomized Controlled Trials as Topic; Renal Insufficiency; Tumor Lysis Syndrome; Urate Oxidase; Uric Acid

Tumour lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Preliminary reports suggest that urate oxidase is effective in reducing serum uric acid, the build-up of which causes TLS. It is uncertain whether high-quality evidence exists to support its routine use in children with malignancies.. To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies.. This is an update of the original review. We performed a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library issue 1, 2013), MEDLINE (1966 to February 2013), Embase (1980 to February 2013), and CINAHL (1982 to February 2013). In addition, we searched the reference lists of all identified relevant papers. We also explored other internet sources (updated search on 26 February 2013): the NHS' National Research Register, the US National Institutes of Health Ongoing Trials Register, the metaRegister of Controlled Trials, and ProQuest Dissertations & Theses Database. We also screened conference proceedings of the American Society of Clinical Oncology, the European Society for Medical Oncology, and the International Society of Paediatric Oncology meetings from 1993 to 2012. Finally, we contacted experts in the field and the manufacturer of rasburicase, Sanofi-aventis.. Randomised controlled trials (RCT) and controlled clinical trials (CCT) of urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy.. Two review authors independently extracted trial data and assessed individual trial quality. We used risk ratios (RR) for dichotomous data and mean difference (MD) for continuous data.. We included seven trials, involving 471 participants in the treatment groups and 603 participants in the control groups. One RCT and five CCTs compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase for the prevention of TLS.The RCT showed no significant difference in mortality (both all-cause mortality and mortality due to TLS), renal failure, and adverse effects between the treatment and the control groups. The frequency of normalisation of uric acid at four hours (Fisher's exact test P < 0.001) and area under curve of uric acid at four days (MD -201.00 mg/dLhr, 95% confidence interval (CI) -258.05 mg/dLhr to -143.95 mg/dLhr; P < 0.00001) were significantly better in the treatment group. The trial did not evaluate the primary outcome (incidence of clinical TLS).Pooled results of three CCTs showed significantly lower mortality due to TLS in the treatment group (RR 0.05, 95% CI 0.00 to 0.89; P = 0.04); all-cause mortality was not significantly different between the groups. Pooled results from five CCTs showed significantly lower incidence of renal failure in the treatment group (RR 0.26, 95% CI 0.08 to 0.89; P = 0.03). Results of CCTs also showed significantly lower uric acid in the treatment group at two days (three CCTs), three days (two CCTs), four days (two CCTs), and seven days (one CCT) after therapy, but not one day (three CCTs), five days (one CCT), and 12 days (one CCT) after therapy. Pooled results from three CCTs showed higher frequency of adverse effects in participants who received urate oxidase (RR 9.10, 95% CI 1.29 to 64.00; P = 0.03). One CCT evaluated the primary outcome; no significant difference was identified.Another included RCT, with 30 participants, compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg), which demonstrated no significant difference in uric acid normalisation and uric acid level at four hours). Common adverse events of urate oxidase included hypersensitivity, haemolysis, and anaemia, but no significant difference between treatment groups was identified. No significant difference in mortality (all-cause mortality and mortality due to TLS) and renal failure was identified. The primary outcome was not evaluated.All included trials were highly susceptible to biases.. Although urate oxidase might be effective in reducing serum uric acid, it is unclear whether it reduces clinical tumour lysis syndrome, renal failure, or mortality. Adverse effects might be more common for urate oxidase compared with allopurinol. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing mortality or renal failure from TLS against the potential risk of adverse effects.

Topics: Adolescent; Allopurinol; Antimetabolites; Area Under Curve; Child; Controlled Clinical Trials as Topic; Humans; Neoplasms; Randomized Controlled Trials as Topic; Renal Insufficiency; Tumor Lysis Syndrome; Urate Oxidase; Uric Acid

Tumor lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Preliminary reports suggest that urate oxidase is highly effective in reducing serum uric acid. It is uncertain whether high quality evidence exists to support its routine use in children with malignancies.. We aimed to determine the effectiveness and safety of urate oxidase in the prevention and treatment of TLS in children with malignancies.. We performed a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library issue 2, 2009), MEDLINE (1966 to 2009), EMBASE (1980 to 2009) and CINAHL (1982 to 2009).. Randomized controlled trials (RCT) and controlled clinical trials (CCT) evaluating urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy.. Two review authors independently extracted trial data and assessed individual trial quality. We used relative risk (RR) for binary data and mean difference (MD) for continuous data.. We included five trials, involved 336 patients in the treatment groups and 458 patients in the control groups. One RCT and three CCTs compared urate oxidase and allopurinol. Two trials tested Uricozyme and two tested rasburicase for the prevention of TLS. The RCT showed no significant difference in mortality or renal failure between the treatment and the control groups. The frequency of normalization of uric acid (RR 19.09, 95% CI 1.28 to 285.41) and area under curve of uric acid (MD -201, 95% CI to -258.05 to -143.95) were significantly better in the treatment group. One patient developed hemolysis. One CCT reported significantly lower mortality due to TLS (RR 0.05, 95% CI 0.00 to 0.89) and lower incidence of renal failure (RR 0.13, 95% CI 0.05 to 0.35) in the treatment group. Another CCT found significantly lower uric acid in the treatment group at 72 hours (MD -98.33, 95% CI -170.66 to -26) and 168 hours (MD -103.67, 95% CI -179.00 to -28.34). All included trials are highly susceptible to biases.Another included RCT with 30 patients compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg), which demonstrated similar efficacy in the reduction of uric acid. Adverse events occurred in 20% of patients, including hemolysis, hypersensitivity and anemia.. Although urate oxidase might be effective in reducing serum uric acid, it is still unclear whether this translates into a reduction in mortality or renal failure. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing renal failure or mortality from TLS against the potential risk of adverse effects.

Topics: Allopurinol; Antimetabolites; Child; Controlled Clinical Trials as Topic; Humans; Neoplasms; Randomized Controlled Trials as Topic; Renal Insufficiency; Tumor Lysis Syndrome; Urate Oxidase; Uric Acid

Hyperuricemia caused secondly from acquired disorders which affect production or excretion of uric acid is defined as secondary hyperuricemia. Many conditions are associated with this type of hyperuricemia and are classified into three types according to the underlying pathophysiology, including accelerated purine nucleotide degradation, ATP breakdown and purine de novo biosynthesis as overproductive type, use of drugs affecting renal urate handling and renal insufficiency as underexcretion type, or overintake of alcohol or fructose as mixed type. Determining uric acid clearance and urate excretion is important for pointing out original disorder; however, sometimes the result from correcting causal factor should be waited for to fix up a final diagnosis. Anti-hyperuricemia agents are used according to the pathophysiology.

Topics: Adenosine Triphosphate; Alcoholism; Allopurinol; Diuretics; Gout Suppressants; Humans; Hyperuricemia; Hypoxanthine Phosphoribosyltransferase; Purine Nucleotides; Renal Insufficiency; Uric Acid

Gout is a crystal deposition disease. European and Japanese guidelines of management for gout recommend that serum urate concentration should be maintained below 6.0 mg/dL to promote crystal dissolution leading to prevention of recurrent gouty attack. Although allopurinol is recommended to be an adequate drug for urate lowering therapy in all gouty patients by European guideline, it is desirable that allopurinol is indicated in patients with overproduction type and benzbromarone in patients with underexcretion type, recommended by Japanese guideline. Asymptomatic hyperuricemia dose not equate to gout. As there is no evidence to support treatment of isolated hyperuricemia with urate lowering therapy currently, it is difficult to establish lowering goal of serum urate level in patients with asymptomatic hyperuricemia. Advice regarding lifestyle and treatment of associated comorbidity should be preferred to urate lowering therapy. However, urate lowering therapy may be indicated in high risk patients with hyperuricemia who are suffered from hypertension, diabetes mellitus, ischemic heart disease and renal insufficiency.

Topics: Allopurinol; Benzbromarone; Cardiovascular Diseases; Gout; Gout Suppressants; Humans; Hyperuricemia; Life Style; Patient Care Planning; Practice Guidelines as Topic; Renal Insufficiency; Uric Acid

Since the original recognition of these conditions in 1961, a great deal has been learned about the pathogenesis, clinical manifestations, and appropriate treatment of gout and pseudogout, and the role of crystals in osteoarthritis has been further defined. The variable manifestations of crystal-induced arthritis in elderly populations has led to a greater need for proper diagnosis and treatment strategies for these increasingly common forms of arthritis.

Topics: Aged; Allopurinol; Arthritis; Arthritis, Gouty; Calcium Pyrophosphate; Chondrocalcinosis; Comorbidity; Diagnosis, Differential; Glucocorticoids; Gout; Gout Suppressants; Humans; Hyperuricemia; Osteoarthritis; Renal Insufficiency; Uric Acid

To identify patients with lymphoma at risk for tumor lysis after chemotherapy.. The case records of 102 patients receiving combination chemotherapy for non-Hodgkin's lymphoma (intermediate to high-grade histology) were reviewed. Patients were considered to have "laboratory tumor lysis" if two of the following metabolic changes occurred within 4 days of treatment: a 25% increase in the serum phosphate, potassium, uric acid, or urea nitrogen concentrations, or a 25% decline in the serum calcium concentration. "Clinical tumor lysis" was defined as laboratory tumor lysis plus one of the following: a serum potassium level greater than 6 mmol/L, a creatinine level greater than 221 mumol/L, or a calcium level less than 1.5 mmol/L, the development of a life-threatening arrhythmia, or sudden death.. Laboratory tumor lysis occurred in 42% of patients and clinical tumor lysis in 6%. There was no statistical difference in the frequency of either tumor lysis syndrome among lymphoma subgroups. Clinical tumor lysis occurred more frequently in patients with pretreatment renal insufficiency (serum creatinine level greater than 132 mumol/L) than in patients with normal renal function (36% versus 2%; p = 0.01). The development of azotemia correlated with high pretreatment serum lactate dehydrogenase concentrations (p < 0.01; r2 = 0.11).. Clinically significant tumor lysis is a rare occurrence in patients with lymphoma when they are receiving allopurinol. However, tumor lysis can occur in patients with all types of moderate to high-grade non-Hodgkin's lymphoma. Patients with a high serum lactate dehydrogenase level or renal insufficiency are at increased risk for metabolic complications after chemotherapy and should be closely monitored.

Topics: Acute Disease; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Blood Urea Nitrogen; Burkitt Lymphoma; Creatinine; Humans; Hyperkalemia; Hypocalcemia; L-Lactate Dehydrogenase; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Phosphates; Renal Insufficiency; Retrospective Studies; Risk Factors; Tumor Lysis Syndrome; Uric Acid

Determine the efficacy and safety of daily lesinurad (200 or 400 mg orally) added to allopurinol in patients with serum uric acid (sUA) above target in a 12-month, randomised, phase III trial.. Patients on allopurinol ≥300 mg (≥200 mg in moderate renal impairment) had sUA level of ≥6.5 mg/dL (≥387 µmol/L) at screening and two or more gout flares in the prior year. Primary end point was the proportion of patients achieving sUA level of <6.0 mg/dL (<357 µmol/L) (month 6). Key secondary end points were mean gout flare rate requiring treatment (months 7 through 12) and proportions of patients with complete resolution of one or more target tophi (month 12). Safety assessments included adverse events and laboratory data.. Patients (n=610) were predominantly male, with mean (±SD) age 51.2±10.90 years, gout duration 11.5±9.26 years and baseline sUA of 6.9±1.2 mg/dL (410±71 µmol/L). Lesinurad at 200 and 400 mg doses, added to allopurinol, significantly increased proportions of patients achieving sUA target versus allopurinol-alone therapy by month 6 (55.4%, 66.5% and 23.3%, respectively, p<0.0001 both lesinurad+allopurinol groups). In key secondary end points, there were no statistically significant treatment-group differences favouring lesinurad. Lesinurad was generally well tolerated; the 200 mg dose had a safety profile comparable with allopurinol-alone therapy. Renal-related adverse events occurred in 5.9% of lesinurad 200 mg+allopurinol, 15.0% of lesinurad 400 mg+allopurinol and 4.9% of allopurinol-alone groups, with serum creatinine elevation of ≥1.5× baseline in 5.9%, 15.0% and 3.4%, respectively. Serious treatment-emergent adverse events occurred in 4.4% of lesinurad 200 mg+allopurinol, in 9.5% of lesinurad 400 mg+allopurinol and in 3.9% of allopurinol-alone groups, respectively.. Lesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy and lesinurad 200 mg was generally well tolerated in patients with gout warranting additional therapy.. NCT01493531.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Cardiovascular Diseases; Creatinine; Double-Blind Method; Drug Therapy, Combination; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Renal Insufficiency; Retreatment; Symptom Flare Up; Thioglycolates; Triazoles; Uric Acid; Uricosuric Agents; Young Adult

Assess influences of demographics and co-morbidities of gout patients with or without diabetes on safety and efficacy of urate-lowering agents.. Post-hoc analysis of 312 diabetic and 1957 non-diabetic gout patients [baseline serum urate levels (sUA) ≥8.0 mg/dl] enrolled in a 6-month randomized controlled trial comparing urate-lowering efficacy (ULE) and safety of daily xanthine oxidase inhibitors (XOIs) febuxostat (40 mg or 80 mg) and allopurinol (200 mg or 300 mg). We compared baseline demographic, gout and co-morbid characteristics, ULE, and safety of XOI treatment in diabetic and non-diabetic gout patients. ULE was measured by the proportion of diabetic and non-diabetic patients in each treatment group achieving final visit sUA < 6.0 mg/dl. Safety was monitored throughout the trial.. Diabetic gout patients were older, more frequently female, and had longer gout duration. Co-morbidities were more frequent among diabetic patients: cardiovascular disease; impaired renal function; hyperlipidemia; and obesity (body mass index >30 kg/m²) (p < 0.001 for all comparisons). Febuxostat 80 mg ULE exceeded that of febuxostat 40 mg or allopurinol (p < 0.050) at all levels of renal function, achieving sUA goal range in the majority of diabetic and non-diabetic patients. Diabetics and non-diabetics reported self-limiting diarrhoea and URIs as the most common adverse events.. Despite higher co-morbidity rates in diabetic patients, febuxostat and allopurinol were safe in both groups at the doses tested. Febuxostat 80 mg achieved sUA <6.0 mg/dl more often than febuxostat 40 mg or allopurinol at commonly prescribed doses.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Body Mass Index; Cohort Studies; Comorbidity; Diabetes Complications; Dose-Response Relationship, Drug; Enzyme Inhibitors; Febuxostat; Female; Gout; Gout Suppressants; Humans; Intention to Treat Analysis; Kidney; Lost to Follow-Up; Male; Middle Aged; Obesity; Patient Dropouts; Renal Insufficiency; Thiazoles; Xanthine Oxidase; Young Adult

Allopurinol has been widely used for treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative.. A multicenter, open-label, parallel, between-group comparative study was conducted to investigate the effects of renal function on the pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel inhibitor of uric acid synthesis.. Based on creatinine clearance (Ccr), 29 subjects were assigned to 3 groups: normal renal function (Ccr ≥ 80 mL/min), mild renal dysfunction (80 mL/min > Ccr ≥ 50 mL/min), or moderate renal dysfunction (50 mL/min > Ccr ≥ 30 mL/min). Febuxostat was repeatedly orally administered at a dose of 20 mg/d for 7 days.. Impaired renal function caused a slight increase in systemic exposure to unchanged febuxostat and its oxidative metabolites, but the exposure did not increase through repeated administration. Moreover, renal impairment did not markedly reduce the effects of febuxostat on plasma uric acid levels. There were no clinically significant adverse events even in patients with impaired renal function.. Febuxostat is considered an inhibitor of uric acid synthesis that could be used in patients with mild to moderate renal impairment without dose adjustment.

Topics: Administration, Oral; Adult; Aged; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Febuxostat; Female; Follow-Up Studies; Glomerular Filtration Rate; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Oxypurinol; Renal Insufficiency; Thiazoles; Treatment Outcome; Uric Acid; Xanthine Oxidase; Young Adult

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

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

Renal failure after lower torso ischemia is a serious problem, partly caused by hypotension and indirect reperfusion injury. This injury is partly due to the formation of oxygen free radicals by activated neutrophils. This injury results in albuminuria and renal function impairment. There are indications that free radical damage in indirect reperfusion injury can be diminished by administering extra antioxidants before and during reperfusion.. In this prospective randomised study we have looked at the influence of a multi-antioxidant supplementation on renal function in patients undergoing an elective open infrarenal abdominal aneurysm repair. The patients received either standard treatment (n=22) or standard treatment with additional antioxidants perioperatively (Allopurinol, vitamin E and C, N-acetylcysteine and mannitol). For renal function we have looked at the albumin/creatinine ratio in urine and 24 hr creatinine clearance.. Despite significantly increased serum total antioxidant capacity, the group receiving extra antioxidants showed no decrease in the albumin/creatinine ratio in urine. There was however a significantly higher creatinine clearance in this group at day 2.. The results indicate that the diminished renal function after infrarenal aneurysm repair may be influenced by antioxidant therapy.

Topics: Acetylcysteine; Aged; Albuminuria; Allopurinol; Antioxidants; Aortic Aneurysm, Abdominal; Ascorbic Acid; Female; Humans; Kidney Function Tests; Male; Mannitol; Prospective Studies; Renal Insufficiency; Reperfusion Injury; Vitamin E

Standard therapy in the United States for malignancy-associated hyperuricemia consists of hydration, alkalinization, and allopurinol. Urate oxidase catalyzes the enzymatic oxidation of uric acid to a 5 times increased urine soluble product, allantoin. Rasburicase is a new recombinant form of urate oxidase available for clinical evaluation. This multicenter randomized trial compared allopurinol to rasburicase in pediatric patients with leukemia or lymphoma at high risk for tumor lysis. Patients received the assigned uric acid-lowering agent for 5 to 7 days during induction chemotherapy. The primary efficacy end point was to compare the area under the serial plasma uric acid concentration curves during the first 96 hours of therapy (AUC(0-96)). Fifty-two patients were randomized at 6 sites. In an intent-to-treat analysis, the mean uric acid AUC(0-96) was 128 +/- 70 mg/dL.hour for the rasburicase group and 329 +/- 129 mg/dL.hour for the allopurinol group (P <.0001). The rasburicase versus allopurinol group experienced a 2.6-fold (95% CI: 2.0-3.4) less exposure to uric acid. Four hours after the first dose, patients randomized to rasburicase compared to allopurinol achieved an 86% versus 12% reduction (P <.0001) of initial plasma uric acid levels. No antirasburicase antibodies were detected at day 14. This randomized study demonstrated more rapid control and lower levels of plasma uric acid in patients at high risk for tumor lysis who received rasburicase compared to allopurinol. For pediatric patients with advanced stage lymphoma or high tumor burden leukemia, rasburicase is a safe and effective alternative to allopurinol during initial chemotherapy.

Topics: Adolescent; Allopurinol; Child; Child, Preschool; Creatinine; Drugs, Investigational; Female; Humans; Infant; Kidney; Kinetics; Leukemia; Lymphoma; Male; Recombinant Proteins; Renal Insufficiency; Risk Factors; Treatment Outcome; Tumor Lysis Syndrome; Urate Oxidase; Uric Acid

To evaluate the effect of nonsteroidal anti-inflammatory drug (NSAID) withdrawal on renal function in patients with chronic gout after proper control of hyperuricemia and gouty symptoms.. Patients with chronic gout, who regularly used NSAIDs to control gouty symptoms prior to urate-lowering therapy, were prospectively followed up in an observational study. Risk factors for renal function impairment were recorded, and the clearance of creatinine (Ccr) was initially measured while on colchinine therapy to prevent gouty bouts. Therapy with urate-lowering drugs was started in order to keep serum urate levels under 6.0 mg/dl (275 micromol/l), and the Ccr was monitored during the follow-up period. Final assessment of the renal function was made after 1 year free from gouty bouts and without NSAID therapy during this period.. 87 patients completed a 1-year period of NSAID withdrawal. Low initial Ccr was related to age, hypertension, hypertriglyceridemia and the presence of previous renal diseases. After proper control of gout and NSAID withdrawal during 1 year, the mean Ccr significantly raised from 94 to 104 ml/min. The improvement was especially significant in patients whose initial Ccr was under 80 ml/min. Their mean Ccr rose from 60 to 78 ml/min, and 12 of 29 patients achieved normal Ccr at the end of the study. No risk factor correlated with improvement of the renal function.. Renal function impairment in patients with chronic gout is mainly related to vascular risk factors, but improvement of the renal function was observed after proper control of hyperuricemia and NSAID withdrawal. Optimal control of hyperuricemia and, therefore, of symptoms of gout should be especially considered in patients with vascular risk factors in order to avoid renal function loss due to NSAID use.

Topics: Adult; Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Benzbromarone; Creatinine; Drug Therapy, Combination; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prospective Studies; Renal Insufficiency; Risk Factors; Uric Acid; Uricosuric Agents

This is a case report of a 68-year-old male with severe tophaceous gouty arthritis, diabetes, kidney impairment and ischaemic heart disease. The patient had repeated attacks of acute gout during a 20-year period and excessive tophaceous depositions. Walking was severely hampered by feet deformity and pain. No urate-lowering therapy was initiated despite contacts to several medical specialties. After the diagnosis was established, the patient was finally treated with allopurinol with an obvious beneficial effect on his symptoms and the size of the tophaceous depositions.

Topics: Aged; Allopurinol; Arthritis, Gouty; Delivery of Health Care; Gout Suppressants; Humans; Male; Renal Insufficiency

While rasburicase has shown efficacy to rapidly correct hyperuricemia compared with allopurinol, its overall impact in improving clinically significant outcomes, such as acute kidney injury (AKI), in tumor lysis syndrome (TLS) is unknown. In this retrospective cohort study, we included all hospitalized cancer patients with hyperuricemia and AKI who received rasburicase +/- allopurinol or allopurinol alone from 2009 to 2015. Inverse probability of treatment weighting using propensity score was used to account for potential confounders and to estimate the causal effect associated with differential drug treatment. 150 patients met inclusion criteria; 89 received rasburicase +/- allopurinol and 61 received allopurinol alone. Weighted outcome regression analysis demonstrated that rasburicase was associated with significantly lower mean uric acid nadir at 7 days compared to allopurinol (2.70 versus 5.82 mg/dL, p < 0.01). However, likelihood of renal function recovery (OR = 0.90, p = 0.79), creatinine nadir by 7 days (1.80 versus 1.66 mg/dL, p = 0.51), and final creatinine by 30 days (2.08 versus 2.07 mg/dL, p = 0.98) did not significantly differ. In conclusion, the clinical benefit of rasburicase in promoting renal function recovery in cancer patietns with concurrent hyperuricemia and renal failure remains inconclusive. Our results suggest that correction of hyperuricemia as a surrogate endpoint may not be associated with significant renal function improvement, particularly if renal dysfunction is unrelated to TLS.

Topics: Adult; Allopurinol; Female; Humans; Hyperuricemia; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms; Odds Ratio; Prognosis; Propensity Score; Renal Insufficiency; Retrospective Studies; Treatment Outcome; Tumor Lysis Syndrome; Urate Oxidase; Uric Acid

Severe cutaneous adverse reactions (SCAR) are uncommon and acute and frequently represent a drug reaction. For years, allopurinol use has remained the highest risk factor for SCARs worldwide. There are multiple risk factors for allopurinol-induced SCARs, including genetic and non-genetic factors. Renal failure has been found to be an important factor resulting in allopurinol-induced SCARs with greater severity and poorer prognosis. An 80-year-old female was admitted to our hospital after administration of allopurinol in December 2018. She developed erythaematous skin of the epidermis of the hips, which rapidly extended over the trunk and limbs, resulting in itching and flaking. The presumptive diagnosis was a drug-induced SCAR. Despite treatment with glucocorticoids and kidney support therapy, the skin lesions extended over the entire body. Fortunately, the progression of pruritic erythema was stopped by double-filtration plasmapheresis (DFPP). DFPP was discontinued after the signs of skin inflammation were no longer visible. Her skin, but not kidney function, recovered after 10 days of hospitalization. She tolerated DFPP well without development of any severe complications. We present here a case of allopurinol-induced SCAR, which was successfully treated with DFPP.

Topics: Aged, 80 and over; Allopurinol; Biomarkers; Disease Management; Drug Eruptions; Female; Humans; Plasmapheresis; Renal Insufficiency; Skin; Treatment Outcome

BACKGROUND Gout is a metabolic disease characterized by deposition of monosodium urate (MSU) crystals called tophi. The typical location of tophi is in the joint and will chronically damage the joint. However, there is a rare atypical dermatologic manifestation of tophi that occur extensively in the skin. CASE REPORT A 46-year-old male presented with acute pain in multiple joints. He had a history of gouty arthritis with recurrence attacks, in the past 2 years ago. Over time, he had gradual eruption of multiple tophi and multiple yellowish nodules under his skin which sometimes would ulcerate. Laboratory value showed creatinine 2.3 mg/dL and uric acid 11.5 mg/dL. Ultrasound of the kidney showed nephrocalcinosis appearance. Urate crystal was identified in skin biopsy of the nodules. We diagnosed the patient with chronic tophaceous gout with extensive cutaneous involvement. Given the renal impairment, we gave methylprednisolone 3 doses of 8 mg for 5 days then tapered off, colchicine 0.5 mg every other day and allopurinol 1 dose of 100 mg. The patient had dramatic improvement of his pain and is now being followed up regularly. CONCLUSIONS We describe a rare and severe extensive cutaneous manifestation in a chronic tophaceous gout patient.

Topics: Allopurinol; Arthritis, Gouty; Biomarkers; Colchicine; Glucocorticoids; Gout Suppressants; Humans; Male; Methylprednisolone; Middle Aged; Renal Insufficiency; Skin Diseases

Clinical development of lesinurad, a selective uric acid reabsorption inhibitor, required analysis of lesinurad in plasma from special patient populations.. EMA and FDA bioanalytical method validation guidance have recommended studying matrix effects on quantitation if samples from special patient populations are to be analyzed. In addition to lesinurad (plasma protein binding 98.2%), the matrix effects from special population plasma on the quantitation of verapamil (PPB 89.6%), allopurinol and oxypurinol (PPB negligible) were also investigated.. The plasma from special population patients had no matrix effects on the three quantification methods with stable isotope labeled internal standard, protein precipitation extraction, and LC-MS/MS detection. The validated lesinurad plasma quantification method was successfully applied for the pharmacokinetic evaluations to support the clinical studies in renal impaired patients.. Special population plasma did not affect quantitation of drugs with a wide range of plasma protein binding levels in human plasma. With the confirmation that there is no impact on quantification from the matrix, the bioanalytical method can be used to support the pharmacokinetic evaluations for clinical studies in special populations.

Topics: Allopurinol; Calibration; Chromatography, High Pressure Liquid; Clinical Trials as Topic; Hepatic Insufficiency; Humans; Kidney; Liver; Oxypurinol; Reference Standards; Renal Insufficiency; Renal Reabsorption; Reproducibility of Results; Tandem Mass Spectrometry; Thioglycolates; Triazoles; Uricosuric Agents; Verapamil

Topics: Adenine; Adenine Phosphoribosyltransferase; Allopurinol; Humans; Infant; Kidney Calculi; Renal Insufficiency

Topics: Allopurinol; Antigens, Differentiation, T-Lymphocyte; Drug Eruptions; Female; HLA-B Antigens; Humans; Male; Oxypurinol; Renal Insufficiency

Objectives Cost-effectiveness of febuxostat compared with allopurinol in the treatment of hyperuricemia in patients with gout. Methods Costs, clinical outcomes, and QALYs were estimated using a Markov model. Febuxostat 80 mg and 120 mg sequentially, used as first line and second line therapy, was compared with allopurinol 300 mg. Patients switched to the next treatment in the sequence according to a dichotomous response vs no response (target serum urate level < 6 mg/dl outcome) after 3 months of active treatment. A 3% discount rate and 5-year time horizon were applied.. National Health System. Results The addition of febuxostat to any therapeutic strategy was an efficient option, with incremental cost-effectiveness ratios (ICER) compared with allopurinol 300 mg ranging from €5268-€9737. Conclusions Febuxostat is a cost-effective treatment in Spain for the management of hyperuricemia in gout patients, with ICERs far below accepted Spanish efficiency thresholds (30 000€/QALY).

Topics: Allopurinol; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Markov Chains; Models, Econometric; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Renal Insufficiency; Spain

Topics: Allopurinol; Antigens, Differentiation, T-Lymphocyte; Drug Eruptions; Female; HLA-B Antigens; Humans; Male; Oxypurinol; Renal Insufficiency

Allopurinol, an antihyperuricaemic agent, is one of the common causes of life-threatening severe cutaneous adverse reactions (SCAR), including drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). The prognostic factors for allopurinol-related SCAR remain unclear. This study aimed to investigate the relationship of dosing, renal function, plasma levels of oxypurinol and granulysin (a cytotoxic protein of SJS/TEN), the disease severity and mortality in allopurinol-SCAR.. We prospectively enrolled 48 patients with allopurinol-SCAR (26 SJS/TEN and 22 DRESS) and 138 allopurinol-tolerant controls from 2007 to 2012. The human leucocyte antigen (HLA)-B*58:01 status, plasma concentrations of oxypurinol and granulysin were determined.. In this cohort, HLA-B*58:01 was strongly associated with allopurinol-SCAR (p<0.001, OR (95% CI) 109 (25 to 481)); however, the initial/maintenance dosages showed no relationship with the disease. Poor renal function was significantly associated with the delayed clearance of plasma oxypurinol, and increased the risk of allopurinol-SCAR (p<0.001, OR (95% CI) 8.0 (3.9 to 17)). Sustained high levels of oxypurinol after allopurinol withdrawal correlated with the poor prognosis of allopurinol-SCAR. In particular, the increased plasma levels of oxypurinol and granulysin linked to the high mortality of allopurinol-SJS/TEN (p<0.01), and strongly associated with prolonged cutaneous reactions in allopurinol-DRESS (p<0.05).. Impaired renal function and increased plasma levels of oxypurinol and granulysin correlated with the poor prognosis of allopurinol-SCAR. Allopurinol prescription is suggested to be avoided in subjects with renal insufficiency and HLA-B*58:01 carriers. An early intervention to increase the clearance of plasma oxypurinol may improve the prognosis of allopurinol-SCAR.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Antigens, Differentiation, T-Lymphocyte; Drug Eruptions; Female; Follow-Up Studies; HLA-B Antigens; Humans; Male; Middle Aged; Oxypurinol; Prognosis; Prospective Studies; Renal Insufficiency; Survival Rate; Taiwan; Young Adult

Topics: Allopurinol; Asymptomatic Diseases; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Hypersensitivity Syndrome; Gout; Humans; Hypertension; Hyperuricemia; Renal Insufficiency; Risk Factors

Allopurinol is an effective urate lowering drug, which is usually well-tolerated with no adverse effects in most cases, but about 2% of the treated patients develop a skin rash, and patients may experience severe allopurinol-induced hypersensitivity syndrome.. The aim of the authors was to summarize and present the clinical manifestations of allopurinol-induced hypersensitivity in patients treated at the Department of Dermatology and Allergology, University of Szeged in order to identify potential associations with this syndrome.. Retrospective review of all patients who were referred to the department with allopurinol-induced hypersensitivity syndrome in the last four years.. During four years, 11 patients were treated with allopurinol-induced hypersensitivity syndrome. The average age was 70.3 years. Before the initiation of allopurinol therapy, 36% of patients had already suffered from various degrees of renal impairment, and 72% of them had been taking thiazide diuretics. Cutaneous manifestations were mainly generalized, erythematous, maculopapular exanthemas (9 patients, 82%), and two patients showed signs of erythema multiforme (18%). Asymptomatic hyperuricemia was the indication for allopurinol therapy in all patients.. Allopurinol-induced hypersensitivity syndrome is a severe, life-threatening disease. Administration of allopurinol should be initiated with clear indications in appropriate dose. Old age, underlying renal impairment and concomitant thiazide diuretic intake should be considered as potential risk factors for developing hypersensitivity syndrome.

Topics: Age Factors; Aged; Aged, 80 and over; Allopurinol; Dermatitis, Exfoliative; Drug Eruptions; Drug Hypersensitivity; Erythema Multiforme; Exanthema; Female; Gout Suppressants; Humans; Male; Middle Aged; Parapsoriasis; Renal Insufficiency; Retrospective Studies; Risk Factors; Sodium Chloride Symporter Inhibitors

The association between hyperuricemia and incident heart failure (HF) is relatively unknown.. Of the 5461 community-dwelling older adults, >or=65 years, in the Cardiovascular Health Study without HF at baseline, 1505 had hyperuricemia (baseline serum uric acid >or=6 mg/dL for women and >or=7 mg/dL for men). Using propensity scores for hyperuricemia, estimated for each participant using 64 baseline covariates, we were able to match 1181 pairs of participants with and without hyperuricemia.. Incident HF occurred in 21% and 18% of participants respectively with and without hyperuricemia during 8.1 years of mean follow-up (hazard ratio {HR} for hyperuricemia versus no hyperuricemia, 1.30; 95% confidence interval {CI}, 1.05-1.60; P=0.015). The association between hyperuricemia and incident HF was significant only in subgroups with normal kidney function (HR, 1.23; 95% CI, 1.02-1.49; P=0.031), without hypertension (HR, 1.31; 95% CI, 1.03-1.66; P=0.030), not receiving thiazide diuretics (HR, 1.20; 95% CI, 1.01-1.42; P=0.044), and without hyperinsulinemia (HR, 1.35; 95% CI, 1.06-1.72; P=0.013). Used as a continuous variable, each 1 mg/dL increase in serum uric acid was associated with a 12% increase in incident HF (HR, 1.12; 95% CI, 1.03-1.22; P=0.006). Hyperuricemia had no association with acute myocardial infarction or all-cause mortality.. Hyperuricemia is associated with incident HF in community-dwelling older adults. Cumulative data from our subgroup analyses suggest that this association is only significant when hyperuricemia is a marker of increased xanthine oxidase activity but not when hyperuricemia is caused by impaired renal elimination of uric acid.

Topics: Aged; Aged, 80 and over; Biomarkers; Female; Heart Failure; Humans; Hyperuricemia; Incidence; Kaplan-Meier Estimate; Male; Propensity Score; Renal Insufficiency; Uric Acid; Xanthine Oxidase

Serum creatinine level is the most commonly used indices for assessment of glomerular filtration rate (GFR), even though these indices have been shown to have some limitations in clinical practice. We investigated the diagnostic efficacy of serum cystatin C compared to that of serum creatinine levels and identified the relating factors associated with changes in serum cystatin C levels in gout patients with renal impairment. A total of 68 gouty patients with renal impairment were enrolled in this study. Diagnostic efficacy of serum cystatin C levels was evaluated through non-parametric receiver operating characteristic (ROC) analysis. The risk factors for changes in serum cystatin C levels were confirmed using multivariate regression analysis. With 24-hr urine creatinine clearance (Ccr) as the reference for GFR, 1/cystatin C (r=0.702, P<0.001) showed a significantly higher correlation with Ccr than 1/creatinine (r=0.665, P<0.001). Multivariate correlation analysis demonstrated that the clinical parameters for increased serum cystatin C are a higher stage of chronic kidney disease, older age, use of allopurinol, and lower high density lipoprotein-cholesterol. The area under the curve (AUC) at ROC plots identified that of serum cystatin C was significantly greater than that of serum creatinine (AUC 0.804 of cystatin C and AUC 0.745 of creatinine). The study suggests that serum cystatin C is a reliable endogenous marker for the assessment of renal function or GFR in gout patients with renal impairment.

Topics: Age Factors; Aged; Allopurinol; Area Under Curve; Biomarkers; Cholesterol, HDL; Creatinine; Cystatin C; Glomerular Filtration Rate; Gout; Gout Suppressants; Humans; Male; Middle Aged; Renal Insufficiency; Risk Factors; ROC Curve

To study patterns and predictors of medication use and laboratory monitoring in gout.. In a cohort of veterans with a diagnosis of gout prescribed allopurinol, colchicine or probenecid, quality of care was assessed by examining adherence to the following evidence-based recommendations: (1) whether patients starting a new allopurinol prescription (a) received continuous allopurinol, (b) received colchicine prophylaxis, (c) achieved the target uric acid level of

Topics: Aged; Allopurinol; Biomarkers; Colchicine; Drug Administration Schedule; Drug Monitoring; Female; Gout; Gout Suppressants; Guideline Adherence; Humans; Male; Middle Aged; Practice Guidelines as Topic; Probenecid; Quality of Health Care; Renal Insufficiency; Treatment Outcome; Uric Acid

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Aged; Allopurinol; Angioedema; Diuretics; Drug Hypersensitivity; Exanthema; Gout; Histamine Antagonists; Humans; Hypertension; Hyperuricemia; Liver Failure, Acute; Male; Oxygen Inhalation Therapy; Renal Insufficiency

We describe the case of a 1-year-old boy with partial hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. At his first visit to the hospital, he was diagnosed with hyperuricemia and irreversible renal failure. The misssense mutation Asp185Gly (554A>G) was identified in exon 8 of his HPRT gene, and this mutation was inherited from the mother.

Topics: Allopurinol; Antimetabolites; Creatinine; Electrophoresis, Agar Gel; Humans; Hypoxanthine Phosphoribosyltransferase; Infant; Lesch-Nyhan Syndrome; Male; Metabolic Clearance Rate; Mutation, Missense; Polymorphism, Restriction Fragment Length; Renal Insufficiency; Uric Acid

To examine evidence-based quality indicators (QIs) in US veterans with gout diagnosis, and to examine the effect of demographics, heath care utilization/access, comorbid conditions, or physican characteristics as predictors of quality of gout care.. Using the Minneapolis Veterans Affairs electronic medical record system, we identified a cohort of veterans receiving medication to treat gout between January 1, 1999 and December 31, 2003, and evaluated 3 recently published evidence-based QIs for gout management: QI 1 = allopurinol dose <300 mg in gout patients with renal insufficiency, QI 2 = uric acid check within 6 months of starting a new allopurinol prescription, and QI 3 = complete blood count and creatine kinase check every 6 months for gout patients receiving prolonged colchicine therapy. We calculated the proportion of patients whose therapy adhered to each QI and to all applicable indicators (overall physician adherence). Logistic regression analysis examined association of overall physician adherence with sociodemographics, health care utilization, comorbidity, and provider characteristics.. Of 3,658 patients with a diagnosis of gout, 663 patients qualified for examination of >/=1 QI. Of these 663 patients, therapy in only 144 (22%) adhered to all applicable QIs; 59 (78%) of 76 adhered to QI 1, 155 (24%) of 643 adhered to QI 2, and 18 (35%) of 52 adhered to QI 3. Overall physician adherence to QIs was significantly lower in older veterans and in those with more inpatient visits per year, but was higher in those with more primary care visits or more health care providers.. Suboptimal physician adherence to QIs was seen for all 3 QIs tested in this cohort of veterans with gout. These findings can guide quality improvement efforts.

Topics: Aged; Allopurinol; Blood Cell Count; Colchicine; Comorbidity; Creatine Kinase; Evidence-Based Medicine; Female; Gout; Gout Suppressants; Guideline Adherence; Humans; Male; Minnesota; Practice Guidelines as Topic; Professional Practice; Quality Indicators, Health Care; Quality of Health Care; Renal Insufficiency; Uric Acid; Veterans

To record practice patterns of treatment of acute gout in hospitalized patients.. We performed a retrospective chart review of hospitalized patients diagnosed with gout.. Seventy-nine (43%) patients were diagnosed with acute gout during their hospitalization. Fifty-eight (73%) patients with acute gout were found to have a reduction in their glomerular filtration rate. Twenty patients (25%) underwent arthrocentesis. The most widely used drugs for acute gout were colchicine, n = 42 (53%), and nonsteroidal antiinflammatory drugs (NSAID), n = 40 (51%). Combination therapy was used in 52% of patients with acute gout. Thiry-six (86%) patients treated with colchicine and 32 (80%) patients treated with NSAID had renal failure.. Crystal analysis, the gold standard for diagnosing gout, was performed in only 25% of patients suspected of acute gout. Combination antiinflammatory agents are used in over 50% of patients despite the absence of evidence to support use of such combinations. Renal failure was present in 73% of patients with acute gout. Colchicine and NSAID should therefore be used with caution in these patients. Practice patterns vary widely and often appear to be in conflict with recommended diagnostic and treatment measures for acute gout.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Colchicine; Drug Therapy, Combination; Gout; Gout Suppressants; Hospitalization; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Renal Insufficiency; Retrospective Studies

Standard treatments for visceral leishmaniasis (antimonials, amphotericin B and pentamidine) pose several problems. Failure of antimonials or severe toxicity is particularly troublesome in patients with renal insufficiency. We report a case of visceral leishmaniasis and renal insufficiency successfully treated with fluconazole and allopurinol for 4 months.

Topics: Allopurinol; Antifungal Agents; Antimetabolites; Diabetic Nephropathies; Fluconazole; Humans; Leishmaniasis, Visceral; Male; Middle Aged; Renal Insufficiency

Standard treatments for visceral leishmaniasis (antimonials, amphotericin B and pentamidine) pose several problems. Failure of antimonials or severe toxicity is particularly troublesome in patients with renal insufficiency. We report a case of visceral leishmaniaisis and renal insufficiency successfully treated with fluconazole and allopurinol for 4 months.

Topics: Allopurinol; Animals; Antimetabolites; Antiprotozoal Agents; Diabetic Nephropathies; Drug Therapy, Combination; Fluconazole; Humans; Leishmaniasis, Visceral; Male; Middle Aged; Renal Insufficiency; Treatment Outcome

In the kidney, dystroglycan (DG) has been shown to cover the basolateral and apical membranes of the podocyte. alpha-DG is heavily glycosilated, which is important for its binding to laminin and agrin in the glomerular basement membrane. Furthermore, alpha-DG is negatively charged, which maintains the filtration slit open. Reactive oxygen species (ROS) are known to degrade and depolymerize carbohydrates, and to play a role in several glomerular diseases. Therefore, we evaluated the effect of ROS on the glycosilation of glomerular alpha-DG. By using specific antibodies directed against the core protein or glyco-epitopes of alpha-DG, this was studied in a solid-phase assay, in situ on kidney sections, and in vivo in adriamycin nephropathy. A ligand overlay assay was used to study binding of alpha-DG to its ligands. Exposure to ROS leads to a loss of carbohydrate epitopes on alpha-DG both in vitro and on kidney sections. In the in vitro assays, a decreased binding of deglycosilated alpha-DG to laminin and agrin was found. In adriamycin nephropathy, where radicals play a role, we observed a loss of alpha-DG carbohydrate epitopes. We conclude that deglycosilation of glomerular alpha-DG by ROS leads to disruption of the agrin-DG complex, which in vivo may lead to the detachment of podocytes. Furthermore, loss of negative charge in the filtration slit may lead to foot process effacement of podocytes.

Topics: Agrin; Animals; Cattle; Doxorubicin; Dystroglycans; Glycosylation; Kidney Glomerulus; Laminin; Muscle, Skeletal; Podocytes; Rabbits; Rats; Reactive Oxygen Species; Renal Insufficiency; Xanthine Oxidase

This study was carried out to determine if Ginkgo Biloba Extract (GBE or Egb 761) exerts a beneficial effect against cisplatin-induced renal failure in rats. Sprague Dawley rats were divided into four groups. The first group (control) received orally 1 mL/kg/day of 0.9% saline by an oral carrier vehicle on days 1 to 10. The second group was injected with 7 mg/kg cisplatin intraperitoneally (i.p.) on the fourth day, once only. The third group (vit E+cisplatin) was administered 10 mg/kg/day i.p. vit E on 1 to 10 days with one dose of i.p. cisplatin (7 mg/kg) injection on the fourth day. The fourth group (GBE+cisplatin) was given GBE orally at 100 mg/mL/kg started on the first day up to the tenth day with one dose of cisplatin (7 mg/kg) injection on the fourth day. Cisplatin was found to lead a statistically significant increase in plasma BUN and creatinine levels, as well as urine micro total protein (MTP) levels, leading to acute renal failure (ARF) in rats. Renal xanthine oxidase (XO) activities increased in all groups (statistically significant in cisplatin + GBE-treated rats; P < 0.001). Adenosine deaminase (AD) activities were increased in cisplatin-treated rats, and decreased in cisplatin+GBE-treated (P < 0.041) and cisplatin+vit E-treated (P < 0.005) rats, compared to controls. Malondialdehyde (MDA), nitric oxide (NO) levels and myeloperoxidase (MPO) activities were increased in the kidney tissue of cisplatin-treated rats. Vit E improved plasma creatinine and urine MTP levels, together with tissue MDA, NO levels, and MPO activities. But GBE had no statistically significant effect on those parameters. These results indicate that increased XO, AD and MPO activities, as well as MDA and NO levels play a critical role in cisplatin nephrotoxicity. GBE has been shown to protect against cisplatin-induced nephrotoxicity.

Topics: Adenosine Deaminase; Animals; Antineoplastic Agents; Cisplatin; Ginkgo biloba; History, Ancient; Male; Malondialdehyde; Nitric Oxide; Peroxidase; Plant Extracts; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Vitamin E; Xanthine Oxidase

Topics: Allopurinol; Antimetabolites; Hematologic Neoplasms; Humans; Recombinant Proteins; Renal Insufficiency; Tumor Lysis Syndrome; Urate Oxidase

In most cases gout is the clinical manifestation of familial hyperuricemia. Pathogenesis of hyperuricemia, clinical manifestations, diagnosis and differential diagnosis of hyperuricemia and gout are described. Treatment of hyperuricemia consists of dietary measurements and administration of uric acid lowering drugs, such as allopurinol or uricosuric agents. Nonsteroidal antiinflammatory drugs, colchicine and glucocorticosteroids are the treatment of choice for the acute gout attack. Prophylaxis of acute uric acid nephropathy consists of hydration, urine alkalinization and administration of allopurinol or rasburicase. For treatment of acute uric acid nephropathy rasburicase is the drug of choice.

Topics: Allopurinol; Arthritis, Gouty; Diagnosis, Differential; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Calculi; Prognosis; Purine-Pyrimidine Metabolism, Inborn Errors; Renal Insufficiency; Uricosuric Agents

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

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

Metabolic abnormalities occur relatively frequently in lymphoma patients undergoing chemotherapy. These abnormalities include hyperuricemia, hypercalcemia, hyperphosphatemia, hypocalcemia, hypomagnesemia, hyponatremia, and hyperkalemia. In addition, tumor lysis syndrome can result in several metabolic abnormalities, leading to potential renal failure. If these syndromes are identified promptly, they can be corrected. Guidelines for identifying metabolic abnormalities in lymphoma patients, as well as management suggestions, are presented

Topics: Adult; Allopurinol; Anthracyclines; Cell Division; Creatinine; Enzyme Inhibitors; Humans; Hypocalcemia; Hypophosphatemia; Lymphoma; Male; Renal Insufficiency; Time Factors; Tumor Lysis Syndrome; Urate Oxidase; Uric Acid

A case of gout and secondary amyloid is described. This rare association is described and the literature is reviewed.

Topics: Allopurinol; Amyloid; Amyloidosis; Colchicine; Drug Therapy, Combination; Follow-Up Studies; Gout; Gout Suppressants; Humans; Male; Middle Aged; Recurrence; Renal Dialysis; Renal Insufficiency

Topics: Allopurinol; Drug Hypersensitivity; Humans; Male; Middle Aged; Recurrence; Renal Insufficiency

The experience with 52 episodes of visceral leishmaniasis diagnosed in 43 patients is reported. The most common symptoms were fever (81%), splenomegaly (65%), hepatomegaly (63%), and pancytopenia (73%). In 79% of the patients, CD4+ cell counts were < 100 cells/mm3. Prior or simultaneous diagnosis of AIDS was made in 29 (67%) patients. Diagnosis was considered fortuitous in 19% of the episodes. In 27% of the episodes, the diagnosis was made on the basis of demonstration of parasites outside the reticuloendothelial system, chiefly blood (7 cases) and gastrointestinal mucosa (5 cases). Parasites were frequently observed or cultured from blood (22/37 episodes) or the digestive tract (8/9 episodes). High antimony doses were more effective than low doses in achieving clinical or parasitological cure (rate of cure, 80% vs. 40%, p = 0.11). Severe toxicity was observed in six (11.7%) of the 51 treated episodes. Severe AIDS-related diseases [odds ratio (OR) 10, p < 0.05] and CD4+ counts (OR 12, p < 0.05) were independent factors for early death. Prophylaxis with monthly pentamidine was not useful in reducing relapses of visceral leishmaniasis.

Topics: AIDS-Related Opportunistic Infections; Allopurinol; Amebicides; Amphotericin B; Analysis of Variance; Anti-HIV Agents; Antimetabolites; Antimony; Antiprotozoal Agents; Blood; Bone Marrow; CD4-Positive T-Lymphocytes; Cerebrospinal Fluid; Didanosine; Digestive System; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Hepatic Encephalopathy; HIV; Humans; Intestinal Mucosa; Leishmaniasis, Visceral; Lymphocyte Count; Male; Myocarditis; Neutrophils; Pancreatitis; Pentamidine; Renal Insufficiency; Spain; Zidovudine

Allopurinol is used frequently to treat patients with gout and hyperuricemia. However, adverse effects associated with this agent have been reported occasionally, especially among patients with hyperuricemia complicated with renal diseases. A rise in the blood concentration of oxipurinol, the chief active metabolite of allopurinol, has been noted in patients with renal dysfunctions, pointing to an implication of oxipurinol toxicity. It has been reported that monitoring the serum oxipurinol concentration to maintain in level below 15.2 micrograms/ml (= 100 mumol/l: recommended level) is helpful in avoiding toxicity. At Jikei University Hospital, a survey was conducted on 148 hyperuricemic patients who had been treated with allopurinol at the dosages of 50, 100, 200 and 300 mg daily or 100 mg on alternate days for more than one month. Because oxipurinol is an uricosuric substance, the steady-state serum oxipurinol concentration was determined by HPLC; and creatinine clearance (CCr) was calculated for each patient. 1. In the group composed of patients with normal kidney function (CCr > or = 80 ml/min), increase in the dosage of allopurinol was associated with a linear increase in the serum concentration of oxipurinol. 2. Among the patients with varying renal function who were receiving 100 mg of allopurinol daily, the oxipurinol level increased logarithmically as the creatinine clearance decreased. In some of the patients with renal insufficiency (CCr < 30 ml/min), daily administration of 100 mg of allopurinol resulted in a serum concentration of oxipurinol over 15.2 micrograms/ml. 3. For patients with renal insufficiency (CCr < 30 ml/min), administration of allopurinol at the dosage of 50 mg/day is considered adequate to avoid the accumulation of serum oxipurinol.

Topics: Adult; Aged; Allopurinol; Antimetabolites; Drug Administration Schedule; Female; Humans; Kidney; Male; Middle Aged; Oxypurinol; Renal Insufficiency; Uric Acid

Topics: Adenosine; Allopurinol; Elective Surgical Procedures; Emergencies; Female; Glutathione; Humans; Hypertonic Solutions; Insulin; Ischemia; Liver; Liver Transplantation; Male; Organ Preservation; Organ Preservation Solutions; Postoperative Complications; Probability; Prognosis; Raffinose; Renal Insufficiency; Retrospective Studies; Risk Factors; Time Factors