238-OR: Changes In Renal Function after Islet Transplantation in a Single-Centre Cohort in Canada over 20 Years

Abstract

Islet transplantation (ITx) is an established treatment for recurrent, severe hypoglycemia in type 1 diabetes, but requires lifelong immunosuppression (IS) which can be nephrotoxic. We examined long term changes in renal function after ITx, through estimated GFR (eGFR), in a single centre cohort followed for up to 20 years. We used data from adults undergoing islet after kidney or ITx alone (94%) at the University of Alberta Hospital between March 11 1999 and Oct 1 2019 with >1 year of follow up. IS included tacrolimus and sirolimus/mycophenolate, balancing side effects with graft and renal function. We calculated individuals mean CKD EPI eGFR (ml/min/1.73m2) at baseline (≤1y pre transplant), 6m and yearly timepoints across follow up. We assessed the overall slope/year of eGFR against time from first transplant in 3 time periods; ≤1y, 1-5y and 5-20y, using mixed effects models. We also compared slopes between subjects with preserved (>60, n=217) vs. reduced (<60, n=38) eGFR at baseline. We included 255 adults (42% M) followed for 88.3m [50.2, 144.9] (median [IQR]). Whole cohort eGFR declined over follow up, most rapidly in the first year; -28.3 [-31.8, -24.5], with slower decline later post transplant 1-5y; -2.9 [-3.5, -2.3] and 5-20y; -1.2 [-1.4, -1.04]. Those with preserved baseline eGFR experienced steeper decline across all time phases as compared to those with reduced eGFR, with the steepest decline ≤1y post transplant (-29.8 [-33.8, -25.9], -18.3 [-27.8, -8.9], p=0.027). Between 5-20y post transplant renal function continued to decline slowly in those with preserved baseline eGFR but was stable in those with reduced baseline eGFR, (-1.4 [-1.6, -1.2], 0.2 [-0.3, 0.7] p<0.001). Nine (3.5%) developed ESRD. Initiation of IS associates with a rapid decline in eGFR the first year post ITx, with minimal decline beyond 5y. With careful IS management, rates of eGFR decline are not greater in those with reduced baseline eGFR. Effective IS regimens without nephrotoxicity remain an important goal. Disclosure A.L.J.Carr: None. A.Shapiro: n/a. P.A.Senior: Advisory Panel; Novo Nordisk Canada Inc., Consultant; Novo Nordisk Canada Inc., Bayer Inc., Viatris Inc., Vertex Pharmaceuticals Incorporated, ViaCyte, Inc., Insulet Corporation. B.A.Marfil-garza: None. Y.Ling: None. R.A.Oram: Consultant; Janssen Research & Development, LLC, Research Support; Randox R & D. A.Lam: None. B.L.Anderson: None. D.O'gorman: None. T.Kin: None. D.Bigam: None.