Cyclosporine-associated chronic nephropathy.
We evaluated glomerular filtration in 17 recipients of heart transplants who were treated for 12 months or longer with cyclosporine (cyclosporin A). The control group consisted of 15 heart-transplant recipients who were treated with azathioprine and who had also survived for at least 12 months. Despite an equivalent cardiac output, the glomerular filtration rate was depressed (51 +/- 4 vs. 93 +/- 3 ml per minute, P less than 0.005) in transplant recipients treated with cyclosporine. Cyclosporine treatment was also associated with reduced renal plasma flow (320 +/- 21 vs. 480 +/- 30 ml per minute, P less than 0.001). A trend toward restricted transglomerular transport of neutral dextrans (radii, 2.4 to 5.8 nm) in cyclosporine-treated recipients suggested an intrinsic loss of ultrafiltration capacity by glomerular capillaries rather than a hemodynamic basis for the reduced glomerular filtration rate. Histopathologic examination of the kidneys of five cyclosporine-treated patients with glomerular hypofiltration revealed a variable degree of tubulointerstitial injury accompanied by focal glomerular sclerosis. Among the 32 heart-transplant recipients treated for more than 12 months with cyclosporine at our center, end-stage renal failure developed in 2. We conclude that long-term cyclosporine therapy may lead to irreversible and potentially progressive nephropathy. We recommend that cyclosporine be used with restraint and caution until ways are found to mitigate its nephrotoxicity.
D000328:Adult; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D016027:Heart Transplantation; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000648:ultrastructure; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D012079:Renal Circulation / Q000187:drug effects
D003524:Cyclosporins; D003404:Creatinine