4.6 Article

Amlodipine reduces cyclosporin-induced hyperuricaemia in hypertensive renal transplant recipients

Journal

NEPHROLOGY DIALYSIS TRANSPLANTATION
Volume 18, Issue 10, Pages 2147-2153

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfg341

Keywords

amlodipine; calcium channel blockade; cyclosporin A; gout; hyperuricaemia; renal transplantation

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Background. Hypertension and hyperuricaemia are common side-effects of cyclosporin A (CsA) treatment in renal transplant recipients. While it is well established that the calcium channel blocker amlodipine can control CsA-induced hypertension effectively in this patient population, recent evidence suggests amlodipine might also reduce hyperuricaemia. The present study was designed to compare the effects of the calcium channel blocker amlodipine (5-10mg/day) and the beta-adrenoceptor antagonist tertatolol (5-10mg/day) on CsA-induced hyperuricaemia in post-renal transplant recipients with hypertension. Methods. Forty-eight hypertensive renal transplant recipients on a stable dose of CsA were randomized in a double-blind, parallel-group manner to receive either amlodipine (n = 24) or tertatolol (n = 24) for 60 days. The primary outcome measure was the change from baseline in serum uric acid concentration. Secondary analyses of efficacy were based on changes in renal function and blood pressure. Results. Amlodipine significantly decreased serum uric acid levels from 483 +/- 99 to 431 +/- 10 mumol/l (P < 0.001), while tertatolol significantly increased uric acid from 450 98 to 476 84 mumol/l (P = 0.006). Amlodipine also significantly increased glomerular filtration rate (P = 0.0048) and the clearance rate of uric acid (P=0.023) and it reduced the fractional proximal tubular reabsorption of sodium (P < 0.001), compared with tertatolol. Renal plasma flow and filtered fraction were unaffected by both treatments, as was trough CsA blood concentration. Amlodipine lowered systolic blood pressure to a significantly greater extent than did tertatolol (P=0.007). The time-dependent profile of diastolic blood pressure did not differ significantly between treatment groups. Both drugs were well tolerated. Conclusions. Amlodipine could be more appropriate than tertatolol for CsA-induced hypertension and hyperuricaemia in renal transplant recipients.

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