CHRONIC CYCLOSPORINE-A NEPHROTOXICITY IN HEART-TRANSPLANTATION

We studied Cyclosporine-A (CyA)-induced nephrotoxicity in 19 stable heart transplant or heart and lung transplant patients, for a mean follow-up time of 15 months (between 4 and 26 months). All of them had normal cardiac function, and none of them presented clinical or histological rejection symptoms. Mean CyA doses were, at 3 and 12 months, 5.1 +/- 0.3 mg/kg/day and 3.8 +/- 0.28 mg/kg/day, with plasma levels of 137 +/- 26 ng/ml vs with 85 +/- 16 ng/ml respectively. The following were measured prospectively: plasma creatinine (pCr), creatinine clearance (CrCl), plasma renin activity (PRA), aldosterone (A) and microalbuminuria. The glomerular filtration rate (GFR), renal plasma flow (RPF) filtration fraction (FF) were determined using isotopic methods. No meaningful changes in pCr or CrCl were noticed during the study, but there was marked decrease in GFR and RPF, isotopically measured, between 3 and 12 months of evolution: 102.5 +/- 9.8 vs 60.5 +/- 10.5 ml/min and 411.7 +/- 40.3 vs 320.5 +/- 49 ml/min respectively, with no further decrease. The FF was high during the first months, subsequently decreasing to 20% after a year of evolution. No patient showed proteinuria; microalbuminuria at 18 months was 10.4 +/- 6-mu-g/ml. After 9 months, 57.8% of patients showed hypertension in spite of a progressive decrease in PRA and A levels. Five patients who received captopril showed a clear decrease in the GFR and the FF, compared to those who did not receive it. Our data suggest that CyA-induced nephrotoxicity is not a limiting factor in middle-term heart transplant evolution when doses between 3 and 5 mg/kg/day are used. However, CrCl overestimates by more than 30% the true GFR, so neither pCr nor CrCl are good parameters for renal function evaluation in these patients. The decrease in RPF conditions a fall in GFR and glomerular hypertension, which partially compensates it during the first months. Captopril may lead to a loss in this compensation mechanism. Hypertension is frequent and seems independent of the renin-aldosterone system.