Renal effects of captopril, indomethacin and nifedipine in nephrotic patients after an oral protein load

Background. In this study we investigated whether the increase in proteinuria induced by an oral protein load may be prevented by the angiotensin-converting enzyme inhibitor (ACEI) captopril in patients with nephrotic syndrome, and whether the effects of captopril on renal haemodynamics and/or glomerular selectivity are comparable to those obtained with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin and the calcium-channel blocker (CaCB) nifedipine. Methods. Twelve subjects underwent the following treatments : (1) low-protein meal (0.2 g protein/kg body wt), (2) high-protein meal (1.3 g protein/kg body wt), (3) high-protein meal plus oral captopril (50 mg), (4) high-protein meal plus oral nifedipine (10 mg), (5) high-protein meal plus oral indomethacin (50 mg). Urine and blood samples were obtained after meals and tested for total protein, immunoglobulin G and albumin. GFR and renal plasma flow (RPF) were calculated from iothalamate and p-aminohippuric acid clearances respectively. Results. Mean arterial pressure decreased significantly after both captopril (-4%, P=0.001) and nifedipine (-5%, P=0.0019). Compared with the low-protein meal, mean values of GFR and RPF increased significantly after the high-protein meal alone (+21%, P= 0.0002 ; +10%, P=0.0491 respectively) and after captopril (+18%, P=0.0025 ; +24%, P=0.0034 respectively) or nifedipine administration (+30%, P=0.0001 ; +21%, P=0.0036 respectively), whereas they remained unchanged after the high-protein meal plus indomethacin administration. FF did not change significantly under the five experimental conditions. The increase in urinary protein excretion induced by the meat load (total protein +18%, P=0.0102 ; albumin +26%, P= 0.0316 ; IgG +28%, P=0.0203) was entirely blocked by both captopril and indomethacin, whereas it was further increased by nifedipine administration. Conclusions. Both captopril and indomethacin, but not nifedipine, are able to prevent the increase in urinary protein excretion rate following a meat meal. The antiproteinuric effect of captopril is comparable to that of indomethacin, but the renal haemodynamic changes induced by these drugs differ considerably, because the filtration capacity and the renal functional reserve were preserved by captopril and decreased by indomethacin. The reduction in systemic blood pressure following administration of both captopril and nifedipine does not account for changes in proteinuria, since, with a similar degree of blood pressure lowering, urinary protein excretion is reduced by captopril and increased by nifedipine.