Amlodipine reduces cyclosporin-induced hyperuricaemia in hypertensive renal transplant recipients.
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 (5-10 mg/day) and the beta-adrenoceptor antagonist tertatolol (5-10 mg/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 +/- 110 microM/l (P < 0.001), while tertatolol significantly increased uric acid from 450 +/- 98 to 476 +/-84 microM/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.
D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage*; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D033461:Hyperuricemia / Q000139:chemically induced / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage*; D012016:Reference Values; D018570:Risk Assessment; D013876:Thiophenes / Q000008:administration & dosage*; D014181:Transplantation Immunology; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage
D007166:Immunosuppressive Agents; D011412:Propanolamines; D013876:Thiophenes; D014665:Vasodilator Agents; D017311:Amlodipine; D016572:Cyclosporine; C005632:tertatolol