Influence of cyclosporin A (CyA) on renal handling of urate

Abstract

Hyperuricaemia is a frequent side-effect of cyclosporin A (CyA) therapy in renal transplant patients, [1,[5][6][7]11], and gout arthritis is the cause of considerable morbidity among these patients [5,7,8,10,11]. However, neither the potential predisposing factors nor the mechanisms of hyperuricaemia have been clearly elucidated. It has been reported that hyperuricaemia in patients on Cy A is associated with a lowered glomerular filtration rate, or with areduced urate clearance [2,5,7,8,10], due to an increase in the net tubular urate reabsorption or to a decrease in secretion [2, 5]. These conclusions are mostly supported by measurements of the basal clearance rate and fractional excretion of urate, but more precise studies of renal handling of urate by the renal tubule have seldom been performed [2]. The purpose of our study was to investigate the prevalence of hyperuricaemia in our population of renal transplant patients, as well as the risk factors involved. Furthermore, we have evaluated the mechanism of hyperuricaemia by a combined pyrazinamide and probenecid test allowing a better evaluation of urate transport processes than pyrazinamide alone. Patients and methods~or the hyperuricemia prevalence study, 169 renal transplant-patients were selected, all of whom had stable graft function and serum creatinine lower than 2 mgldl. The group comprised 96 males and 73 females, with a mean age of 38 ± 12 years, 80 on azathioprine (Aza) and 89 on CyA. Patient records were reviewed and the following data collected at 12 months: serum and urine urea, creatinine ~nd urate, serum potassium and total C02 and the drugs taken at this time. Hyperuricaemia was considered to be present when serum

Associations between Hyperuricemia and Chronic Kidney Disease: A Review

“…It has been strongly associated with the development of HUA and gout ( 41 ). However, the mechanism for Cyclosporine’s strong association with HUA is unclear and may include an inhibitory effect on urate secretion ( 42 ). Tacrolimus also commonly is used in transplantation immunosuppressive regimens and has been reported to increase serum urate levels in a manner similar to Cyclosporine ( 43 ).…”

Management of Hyperuricemia and Gout in CKD

“…It has been strongly associated with the development of hyperuricemia and gout. 5 However, the mechanism for cyclosporine's strong association with hyperuricemia is unclear and may include an inhibitory effect on urate secretion, 29 stimulation of urate reabsorption, 30 or through a decreased glomerular filtration rate. 31 Tacrolimus also commonly is used in transplantation immunosuppressive regimens and has been reported to increase serum urate levels in a manner similar to cyclosporine.…”

Allopurinol to Febuxostat: How far have we come?

“…Other, commonly used drugs have been identified as potentially causing decreased uric acid excretion including diuretics, ethanol, low-dose aspirin, and laxatives (when used excessively). [31][32][33][34][35][36][37][38][39][40][41] Decreased uric acid excretion is particularly troublesome for gout patients treated with allopurinol, as this agent has been associated with renal impairment during treatment.…”