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Cyclosporine-associated chronic nephropathy
Insights
Long-term cyclosporine therapy in heart transplant recipients significantly impairs glomerular filtration and renal plasma flow. This immunosuppressant may cause irreversible nephropathy, necessitating cautious use.
Area of Science:
- Nephrology
- Transplantation Immunology
- Pharmacology
Background:
- Cyclosporine (cyclosporin A) is a vital immunosuppressant in organ transplantation.
- Long-term effects of cyclosporine on renal function in heart transplant recipients require further investigation.
Purpose of the Study:
- To evaluate the impact of long-term cyclosporine therapy on glomerular filtration rate (GFR) and renal hemodynamics in heart transplant recipients.
- To investigate the potential for cyclosporine-induced nephropathy.
Main Methods:
- Compared GFR and renal plasma flow in 17 heart transplant recipients on cyclosporine (≥12 months) versus 15 on azathioprine (≥12 months).
- Assessed transglomerular transport of neutral dextrans and performed kidney histopathology.
- Monitored for end-stage renal failure in a cohort of 32 long-term cyclosporine users.
Main Results:
- Cyclosporine recipients showed significantly depressed GFR (51 vs. 93 ml/min) and reduced renal plasma flow (320 vs. 480 ml/min) despite equivalent cardiac output.
- Evidence suggested intrinsic glomerular capillary dysfunction rather than hemodynamic factors.
- Histopathology revealed tubulointerstitial injury and focal glomerular sclerosis; 2/32 patients developed end-stage renal failure.
Conclusions:
- Long-term cyclosporine therapy is associated with significant nephrotoxicity in heart transplant recipients.
- This nephropathy may be irreversible and progressive.
- Cyclosporine should be used cautiously, and strategies to mitigate its renal toxicity are needed.
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.