Modifying cyclosporine associated renal allograft dysfunction

Transplantation is accepted therapy for chronic kidney disease. However the essential immunosuppressive agents for graft survival have their own side-effects. Renal biopsy is a reliable tool for diagnosing cyclosporine (CsA) nephrotoxicity. To present our observations on CsA toxicity in renal allograft biopsies, we studied prospectively 207 renal allograft biopsies performed for graft dysfunction as per Ahmedabad Tolerance Induction Protocol (ATIP) and compared them to 50 controls from January to October 2007. The ATIP comprised donor specific leucocyte infusions, low dose target specific irradiation; non-myeloablative condi-tioning with Anti-T +/- B cell antibodies followed by intraportal administration of cultured donor bone marrow (BM) +/- adipose tissue derived mesenchymal stem cells. Renal transplantation was performed following negative lymphocytotoxicity cross-matching. The post-transplant immunosuppressive agents included CsA 2.5 +/- 0.5 mg/kg BW/day and prednisone 0.2 mg/kg BW/day. The controls were transplanted using standard triple immunosuppressive agents including CsA 5 +/- 1 mg/Kg BW/day, prednisone 0.6 mg/kg BW/day, and MMF/ Azathioprine. The Institutional Review Board approved the ATIP. The biopsies were categorized into 2 groups; group A (N=97): performed < 6 months, group B (N= 160), > 6 months posttransplant. Acute CsA toxicity was observed in group A: 2.5% ATIP and 11.1% controls; group B: 16.2% ATIP and 8.8% controls. Chronic CsA toxicity was observed in group B: 10.8 % ATIP and 17.6 % controls. Acute toxicity was more in the ATIP, while chronic toxicity was more in the controls. CsA doses were reduced post-biopsy and resulted in improved graft function evaluated by serum creatinine. We conclude that CsA nephrotoxicity evaluated by allograft biopsy resulted in allograft function recovery by decreasing the cyclosporine dose, and the ATIP decreased the incidence of CsA nephrotoxicity.