Proteinuria After Conversion to Sirolimus in Renal Transplant Recipients G.M. Sahin, S. Sahin, G. Kantarci, and H. Ergin ABSTRACT Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi’s sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78  42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20  12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98  0.8 mg/dL before SRL therapy and 2.53  1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi’s sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy. S IROLIMUS (SRL) is a new potent immunosuppressive agent. 1 SRL blocks an intracellular kinase (mTOR) that regulates the growth and proliferation of lymphocytes. Sirolimus is not nephrotoxic 2,3 and is not associated with hypertension as compared with cyclosporine treatment. 4 SRL possess an antiangiogenic effect. 5 The absence of nephrotoxicity, the favorable effects in posttransplant hyper- tension, and the antiproliferative effects address problems associated with other immunosuppressants: chronic allograft nephropathy CAN, cardiovascular mortality, and cancer. Recently conversion from calcineurin inhibitor (CNI) to SRL has become an option for patients with CAN or other conditions, such as posttransplant tumors. However, SRL may cause other side effects, such as hyperlipidemia, 6 mouth ulcers, 7 disturbed wound healing, 8 and thrombotic microangiopathy. 9 More recently, proteinuria has been reported to be a consequence of SRL therapy, although the mechanism has remained unclear. 10 –12 The aim of this From the Department of Nephrology, Goztepe Research and Teaching Hospital, Istanbul, Turkey. Address reprint requests to Dr Gulizar Manga Sahin, Libadiye cad. Tahrali sit. Samyeli B Blok D:28 Uskudar, Istanbul, Turkey. E-mail: gulimanga@yahoo.com © 2006 by Elsevier Inc. All rights reserved. 0041-1345/06/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2006.10.152 Transplantation Proceedings, 38, 3473–3475 (2006) 3473