Effect of nifedipine on tubular handling of uric acid in transplanted kidney on cyclosporine A treatment.
Hyperuricemia resulting from tubular urate transport defects is a well-known nephrotoxic effect of cyclosporine A (CyA) on renal blood perfusion in organ recipients. The aim of this study was to define the mechanism of the tubular urate transport defect in hyperuricemic renal graft recipients on CyA and to evaluate the effect of nifedipine retard administration on this tubular dysfunction. Tubular uric acid transport was evaluated by the probenecid test in 17 hyperuricemic (group 1) and 6 normouricemic (group 2) renal graft recipients treated with CyA. Maximal urate excretion after probenecid administration was 25.5 +/- 4.6 versus 42.5 +/- 7.7% (p < 0.001) and postsecretory urate reabsorption was 79.2 +/- 8.3 versus 78.5 +/- 9.7% (NS), respectively. The effects of nifedipine retard on renal urate transport were evaluated in 6 hyperuricemic patients. Seven days of nifedipine therapy did not significantly decrease mean serum uric acid levels (7.7 +/- 1.6 to 7.1 +/- 1.1 mg/dl) nor increase urate clearance (3.8 +/- 1.3 to 4.7 +/- 1.6 ml/min/1.73 m2). The uricosuric effect of probenecid was manifested by an increase in tubular urate transport from 25.5 +/- 4.6 to 37.3 +/- 7.2%, p < 0.01, paralleled by an increase in postsecretory urate reabsorption from 20.5 +/- 3.7 to 31.4 +/- 5.7% (p < 0.003). Postsecretory reabsorption expressed as a percentage of secreted urate in both evaluations did not differ significantly (80.3 +/- 6.2 vs. 84.4 +/- 3.1%).(ABSTRACT TRUNCATED AT 250 WORDS)
Zawadzki
J
J
Department of Nephrology, Dialysis and Kidney Transplantation, Child Health Center, Warsaw, Poland.
Grenda
R
R
Januszewicz
P
P
D000293:Adolescent; D000328:Adult; D002648:Child; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D007674:Kidney Diseases / Q000378:metabolism* / Q000628:therapy; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009543:Nifedipine / Q000627:therapeutic use*; D011339:Probenecid / Q000627:therapeutic use; D014527:Uric Acid / Q000097:blood* / Q000652:urine
D003692:Delayed-Action Preparations; D014527:Uric Acid; D016572:Cyclosporine; D003404:Creatinine; D009543:Nifedipine; D011339:Probenecid