Chronic cyclosporine-induced nephrotoxiciy in heart transplant patients: Long-term benefits of treatment with mycophenolate mofetil and low-dose cyclosporine

Background. Cyclosporine-induced nephropathy is a major limitation in heart transplant patients. Cyclosporine dose reduction may lead to substantial early improvement in renal function. Our aim was to study the long-term benefits of therapy with low doses of cyclosporine plus mycophenolate mofetil in heart transplant patients with drug-induced nephrotoxicity. Methods. Twenty-five adult heart transplant patients with cyclosporine-related nephrotoxicity (mean posttransplant 41.7 25.7 months) were included in the retrospective analysis (22 men, mean age 58.8 7.9 years.). Patients were switched from azathioprine to mycophenolate mofetil (1 to 3 g/d), followed by a stepwise reduction in cyclosporine dosage (trough cyclosporine level maintained around 100 ng/mL). Renal function was determined by serial measurements of serum creatinine and glomerular filtration rate at 3-month intervals. Results. With a mean follow-up of 30 13 months, the baseline creatinine of 2.37 0.5 mg/dL decreased to 1.59 0.40 mg/dL (P .0001). The baseline glomerular filtration rate of 36.77 10.10 mL/min improved to 54.98 13.80 mL/min (P .0001). The cyclosporine level was the unique independent variable associated with renal functional improvement (partial R 2 0.4). Within the first 3 months, renal function displayed a rapid improvement after conversion to mycophenolate mofetil (P .001), reaching a plateau, without further significant improvement over the course of time. Conclusions. Cyclosporine-induced nephrotoxicity is not a progressive, irreversible disease. Reduction in cyclosporine exposure by addition of mycophenolate mofetil is useful to achieve long-term renal functional improvement, thereby avoiding chronic renal failure. A unique, significant factor associated with this improvement was the reduction in cyclosporine level.