DIVERGENT EFFECTS OF CALCIUM-CHANNEL AND ANGIOTENSIN-CONVERTING ENZYME BLOCKADE ON GLOMERULOTUBULAR FUNCTION IN CYCLOSPORINE-TREATED RENAL-ALLOGRAFT RECIPIENTS

The effects of amlodipine and perindopril on renal hemodynamics and tu bular function in cyclosporine-treated hypertensive renal allograft re cipients were evaluated in a randomized, double-blind crossover fashio n, Ten patients were studied after a 2-week placebo run-in and, after 8 weeks of active treatment, allowing a a-week placebo washout between treatments, At the end of each period, glomerular filtration rate (GF R) and effective renal plasma flow (ERPF) were measured as Cr-51-EDTA and I-123-hippuran clearance, respectively, and tubular function evalu ated by the lithium clearance technique was determined, Both drugs mai ntained GFR and ERPF and lowered mean arterial pressure (MAP, mm Hg) t o a similar extent (time x treatment, P = 0.466): amlodipine from 126. 9 +/- 2.5 to 115.9 +/- 2.2; perindopril from 126.9 +/- 2.5 to 117.9 +/ - 3.9 (time effect of all treatments together, P = 0.003). Accordingly , renal vascular resistance (RVR, mm Hg/mL/min/1.73 m(2)) was equally reduced (time x treatment, P = 0.955): amlodipine from 0.36 +/- 0.03 t o 0.30 +/- 0.02; perindopril from 0.36 +/- 0.03 to 0.32 +/- 0.01 (time effect all treatments together, P = 0.043), Sodium clearance and frac tional excretion of sodium were not affected by either drug, Output of fluid from the proximal tubules measured as clearance of lithium (C-L i mL/min) and uric acid (C-Urs mL/min) was higher after amlodipine tha n after perindopril (C-Li 19.1 +/- 2.1 v 16.5 +/- 1.7, P = 0.036 and C -Ur 7.0 +/- 0.6 v 5.9 +/- 0.4, P = 0.007). As a consequence, after aml odipine, distal absolute reabsorption of sodium was higher (DAR(Na) 2. 57 +/- 0.28 v 2.19 +/- 0.22 mEq/min, P = 0.027) and serum uric acid wa s lower (5.9 +/- 0.3 v 6.7 +/- 0.4 mg/dL, P = 0.001) in comparision wi th perindopril. In cyclosporine-treated renal allograft hypertensives, amlodipine and perindopril lower blood pressure equally and reduce RV R to the same extent, Overall sodium excretion is not affected by eith er agent. Urate clearance is higher and serum uric acid lower on amlod ipine as compared with perindopril. (C) 1996 by the National Kidney Fo undation, Inc.