Conversion of Cyclosporine to Sirolimus Before 12 Months is Associated With Marked Improvement in Renal Function and Low Proteinuria in a South African Renal Transplant Population

Abstract

Objectives: Avoidance of calcineurin inhibitor-associated nephrotoxicity has recently gained focus. To assess the impact of the conversion to sirolimus, we performed a retrospective audit on renal transplant patients switched to sirolimus at the Inkosi Albert Luthuli Central Hospital (South Africa) from 2003 until June 2007.

Materials and Methods: Medical records of transplant recipients were analyzed. Twenty-four–hour urine protein excretion and estimated glomerular filtration rates before initiation of sirolimus (baseline), and at their last clinic visit, were compared. Patients were then subcategorized according to their specific indications for switching to sirolimus.

Results: Thirty patients were included. Average follow-up was 25 months. Indications for use of sirolimus were group 1 (cyclosporine-induced biochemical toxicity, n=6); group 2 (chronic allograft nephropathy, n=6); group 3 (severe gum hypertrophy, n=9); group 4 (posttransplant diabetes, n=4); group 5 (calcineurin-inhibitor–induced histologic nephrotoxicity, n=2); and group 6 (calcineurin inhibitor associated malignancy, n=3). Average urine protein excretion rate and estimated glomerular filtration rate before starting sirolimus were 0.44 ± 0.08 g/24 h and 50.1 ± 3.1 mL/min respectively, compared to 0.94 ± 0.2 g/24 h and 52.1 ± 4.8 mL/min, at an average follow-up of 25 months. On subgroup analysis, estimated glomerular filtration rate was increased/unchanged in groups 1 (47.3 vs 51.16 mL/min) and 4 (60.0 vs 60.0 mL/min) when compared to baseline, but decreased in groups 2 (47 vs 27.6 mL/min), 3 (51.3 vs 42.2 mL/min), 5 (54.0 vs 29.5 mL/min), and 6 (60.0 vs 56.5 mL/min). Combining the latter 2 groups, most patients (80%) received sirolimus within 1 year of transplant, whereas only 2 patients in the former groups (10%) received the drug within 1 year of transplant.

Conclusions: Overall, sirolimus therapy was associated with improved estimated glomerular filtration rate, and also an increase in urine protein excretion rates. Maximum benefit was achieved when patients were switched to sirolimus within the first transplant year.