Cyclosporine-induced renal dysfunction in human renal allograft recipients.
Cyclosporine-treated renal allograft recipients frequently suffer CsA-related nephrotoxicity and hypertension. This study demonstrates that glomerular filtration rate is reduced acutely by 13% (P less than 0.02) and renal vascular resistance increased by 30% (P less than 0.05), immediately after patients take their CsA dose. The reduction in GFR is directly related to their trough CsA level (r = 0.82; P less than 0.01). The lower the trough CsA level the greater the fall in GFR after the CsA dose. Plasma renin activity does not increase after the CsA dose (pre-CsA 0.6 +/- 0.2 ng/L/sec vs. post-CsA 0.4 +/- 0.1 ng/L/sec; P = NS), and therefore cannot be responsible for the reduction in renal function. Short-term nifedipine treatment is effective in preventing the acute reduction in GFR (P less than 0.05). This occurred despite no apparent effect of nifedipine in altering trough or post-dose CsA levels. Furthermore nifedipine was effective in lowering both the mean arterial blood pressure (109 mmHg to 94 mmHg; P less than 0.01) and the elevated renal vascular resistance (25% reduction; P less than 0.02) observed in these patients. These results suggest that nifedipine may be a suitable agent for limiting acute CsA nephrotoxicity and for treating CsA-associated hypertension in renal allograft recipients.
Kiberd
B A
BA
Department of Medicine, Queen's University, Kingston, Ontario, Canada.
D003524:Cyclosporins / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced; D016030:Kidney Transplantation; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D014184:Transplantation, Homologous
D003524:Cyclosporins; D012083:Renin; D009543:Nifedipine