LONG-TERM IMPROVEMENT IN RENAL FUNCTION AFTER CYCLOSPORINE REDUCTION IN RENAL TRANSPLANT RECIPIENTS WITH HISTOLOGICALLY PROVEN CHRONIC CYCLOSPORINE NEPHROPATHY

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Abstract
Chronic cyclosporine (CsA) nephropathy, which has been unequivocally documented in recipients of heart, heart-lung, liver, or bone marrow transplants, as well as in nontransplant situations, usually results in a progressive deterioration of renal function. In this study, we assessed the potential reversibility of chronic CsA nephropathy in renal transplant recipients. Twenty-three renal transplant patients with biopsy-proven CsA nephropathy associated with long-term CsA administration (27±4 months) were followed up for more than 2 years after CsA reduction (18/23 patients) or withdrawal (5/23 patients) and addition of azathioprine. Changes in effective renal plasma flow and glomerular filtration rate were assessed before and 2 years after CsA reduction, whereas serum creatinine, proteinuria, blood pressure, and CsA concentrations were monitored up to 5 years. At 2-year follow-up, glomerular filtration rate increased from 40±3 to 47±4 ( P <0.05) and effective renal plasma flow from 217±23 to 244±24 ml/min/1.73 m2(NS). Mean arterial pressure significantly decreased from 98.7±2.9 to 93.1±2.7 mmHg ( P <0.05). There was no significant change in renal vascular resistance, filtration fraction, or albumin excretion. A significant decrease in serum creatinine was also observed during the whole follow-up (73±6.5 months). CsA reduction was followed by only one episode of acute reversible rejection; chronic rejection developed in three patients 2 years or later after CsA reduction. These data suggest that CsA nephropathy participates in graft dysfunction in a small group of renal transplant recipients. In addition, graft dysfunction may be reversible when CsA dosage is reduced early after diagnosis of chronic CsA nephropathy.