title: Cyclosporine-associated chronic nephropathy.
abstract: 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.
mesh_terms: 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
chemical_list: D003524:Cyclosporins; D003404:Creatinine