BACKGROUND: We report the 5-year outcomes from a randomized prospective trial in primary adult renal allograft recipients, designed to evaluate calcineurin inhibitor (CNI)-free immunosuppression on kidney transplant function. METHODS:Sixty-one patients were randomized to either sirolimus (n=31) or cyclosporine (n=30) after basiliximab induction and mycophenolate mofetil (MMF) with steroids. Sirolimus was concentration controlled at 10-12 ng/mL for at least 6 months. RESULTS: After 5 years, sirolimus-MMF-steroids compared to cyclosporine-MMF-steroids provides similar patient survival (87.1 vs. 90%, P=0.681), acute rejection rates (12.9 vs. 23.3%, P=0.22), total cholesterol (209.1 vs. 204.3 mg/dL, P=0.973), urine protein/creatinine ratios (0.398 vs. 0.478 mg/dL, P=0.72), and overall medical and surgical morbidity (P=NS). Although unadjusted patient survival was similar, sirolimus based CNI-free patients had longer death censored graft survival (96.4 vs. 76.7%, P=0.0265), higher glomerular filtration rate (GFR) by the abbreviated Modified Diet in Renal Disease (66.7 vs. 50.7 cc/min, P=0.0075), and fewer graft losses from chronic allograft nephropathy. The Banff chronic scores at two years were strong predictors of 5-year GFR. At 5 years, there were six de novo (three solid organ, three skin) cancers in the CNI group and only two de novo (one skin, one leukemia, no solid organ) cancers in the sirolimus group (P=NS). CONCLUSIONS: This study of low to moderate risk patients demonstrates that excellent 5-year kidney transplant outcomes can be achieved without CNI drugs, when therapeutic drug monitoring of sirolimus is employed. The application of CNI drug avoidance protocols to high-risk recipients (retransplants, highly sensitized, etc.), extrarenal allograft recipients, or alternative drug regimens such as steroid or MMF elimination should be subjected to controlled trials.
RCT Entities:
BACKGROUND: We report the 5-year outcomes from a randomized prospective trial in primary adult renal allograft recipients, designed to evaluate calcineurin inhibitor (CNI)-free immunosuppression on kidney transplant function. METHODS: Sixty-one patients were randomized to either sirolimus (n=31) or cyclosporine (n=30) after basiliximab induction and mycophenolate mofetil (MMF) with steroids. Sirolimus was concentration controlled at 10-12 ng/mL for at least 6 months. RESULTS: After 5 years, sirolimus-MMF-steroids compared to cyclosporine-MMF-steroids provides similar patient survival (87.1 vs. 90%, P=0.681), acute rejection rates (12.9 vs. 23.3%, P=0.22), total cholesterol (209.1 vs. 204.3 mg/dL, P=0.973), urine protein/creatinine ratios (0.398 vs. 0.478 mg/dL, P=0.72), and overall medical and surgical morbidity (P=NS). Although unadjusted patient survival was similar, sirolimus based CNI-free patients had longer death censored graft survival (96.4 vs. 76.7%, P=0.0265), higher glomerular filtration rate (GFR) by the abbreviated Modified Diet in Renal Disease (66.7 vs. 50.7 cc/min, P=0.0075), and fewer graft losses from chronic allograft nephropathy. The Banff chronic scores at two years were strong predictors of 5-year GFR. At 5 years, there were six de novo (three solid organ, three skin) cancers in the CNI group and only two de novo (one skin, one leukemia, no solid organ) cancers in the sirolimus group (P=NS). CONCLUSIONS: This study of low to moderate risk patients demonstrates that excellent 5-year kidney transplant outcomes can be achieved without CNI drugs, when therapeutic drug monitoring of sirolimus is employed. The application of CNI drug avoidance protocols to high-risk recipients (retransplants, highly sensitized, etc.), extrarenal allograft recipients, or alternative drug regimens such as steroid or MMF elimination should be subjected to controlled trials.
Authors: Aleksey Nakorchevsky; Johannes A Hewel; Sunil M Kurian; Tony S Mondala; Daniel Campbell; Steve R Head; Christopher L Marsh; John R Yates; Daniel R Salomon Journal: J Am Soc Nephrol Date: 2010-01-21 Impact factor: 10.121
Authors: Kristian L Brown; Olena Y Palyvoda; Jagdish S Thakur; Sandra L Nehlsen-Cannarella; Omar R Fagoaga; Scott A Gruber; Gregory W Auner Journal: Cytometry A Date: 2009-11 Impact factor: 4.355
Authors: Nasrine Bendjilali; Jeffrey Nelson; Shantel Weinsheimer; Stephen Sidney; Jonathan G Zaroff; Steven W Hetts; Mark Segal; Ludmila Pawlikowska; Charles E McCulloch; William L Young; Helen Kim Journal: J Neurol Neurosurg Psychiatry Date: 2014-04-28 Impact factor: 10.154
Authors: Sunil M Kurian; Raymond Heilman; Tony S Mondala; Aleksey Nakorchevsky; Johannes A Hewel; Daniel Campbell; Elizabeth H Robison; Lin Wang; Wen Lin; Lillian Gaber; Kim Solez; Hamid Shidban; Robert Mendez; Randolph L Schaffer; Jonathan S Fisher; Stuart M Flechner; Steve R Head; Steve Horvath; John R Yates; Christopher L Marsh; Daniel R Salomon Journal: PLoS One Date: 2009-07-10 Impact factor: 3.240
Authors: Angela C Webster; Lorenn P Ruster; Richard McGee; Sandra L Matheson; Gail Y Higgins; Narelle S Willis; Jeremy R Chapman; Jonathan C Craig Journal: Cochrane Database Syst Rev Date: 2010-01-20