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.
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[Full Text]
Hickman, P. E., Potter, J. M., Pesce, A. J.
(1997). Clinical chemistry and post-liver-transplant monitoring. Clin. Chem.
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[Abstract][Full Text]
Scott, M. G., Hock, K. G., Crimmins, D. L., Fracasso, P. M.
(1997). HPLC method for monitoring SDZ PSC 833 in whole blood. Clin. Chem.
43: 505-510
[Abstract][Full Text]
van der Heide, J. J. H., Bilo, H., Donker, J.M., Wilmink, J. M., Tegzess, A. M.
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329: 769-773
[Abstract][Full Text]
Denys, B. G., Sudhakar Reddy, P., Urestsky, B. F.
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42: 218-223
[Abstract]
Shannon, K. M., Cowan, M. J., Matthay, K. K.
(1987). Pediatric Bone Marrow Transplantation: Intensive Care Management. J Intensive Care Med
2: 328-344
[Abstract]