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 tubular function in cyclosporine-treated hypertensive renal allograft recipients were evaluated in a randomized, double-blind crossover fashion. Ten patients were studied after a 2-week placebo run-in and, after 8 weeks of active treatment, allowing a 2-week placebo washout between treatments. At the end of each period, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured as 51Cr-EDTA and 123I-hippuran clearance, respectively, and tubular function evaluated by the lithium clearance technique was determined. Both drugs maintained GFR and ERPF and lowered mean arterial pressure (MAP, mm Hg) to 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 m2) was equally reduced (time x treatment, P = 0.955): amlodipine from 0.36 +/- 0.03 to 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 fractional excretion of sodium were not affected by either drug. Output of fluid from the proximal tubules measured as clearance of lithium (CLi, mL/min) and uric acid (CUr, mL/min) was higher after amlodipine than after perindopril (CLi 19.1 +/- 2.1 v 16.5 +/- 1.7, P =0.036 and CUr 7.0 +/- 0.6 v 5.9 +/- 0.4, P = 0.007). As a consequence, after amlodipine, distal absolute reabsorption of sodium was higher (DARNa 2.57 +/- 0.28 v 2.19 +/- 0.22 mEq/min, P = 0.027) and serum uric acid was lower (5.9 +/- 0.3 v 6.7 +/- 0.4 mg/dL, P = 0.001) in comparison with perindopril. In cyclosporine-treated renal allograft hypertensives, amlodipine and perindopril lower blood pressure equally and reduce RVR to the same extent. Overall sodium excretion is not affected by either agent. Urate clearance is higher and serum uric acid lower on amlodipine as compared with perindopril.
Sennesael
J J
JJ
Renal Unit, Academisch Ziekenhuis, Vrije Universiteit Brussel, Belgium.
Lamote
J G
JG
Violet
I
I
Tasse
S
S
Verbeelen
D L
DL
D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000502:physiology; D016030:Kidney Transplantation / Q000502:physiology*; D007684:Kidney Tubules / Q000187:drug effects* / Q000502:physiology; D008094:Lithium / Q000652:urine; D008297:Male; D008875:Middle Aged; D020913:Perindopril; D010919:Placebos; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D012964:Sodium / Q000378:metabolism / Q000652:urine; D014184:Transplantation, Homologous; D014527:Uric Acid / Q000097:blood / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D007211:Indoles; D010919:Placebos; D017311:Amlodipine; D014527:Uric Acid; D016572:Cyclosporine; D008094:Lithium; D012964:Sodium; D020913:Perindopril