336-OR: Females Undergoing Islet Transplantation with CNI-Based Immunosuppression May Be at Higher Risk of Renal Function Decline

Islet transplantation (ITx) is an established treatment for recurrent, severe hypoglycemia in type 1 diabetes, however, requires lifelong immunosuppression (IS) which can be nephrotoxic. We conducted a risk regression to identify factors associated with progression to Stage 3 CKD (S3CKD) or worse post-ITx. We used data from adults undergoing ITx alone at the University of Alberta Hospital between March 11 1999 and Oct 1 2019 with >1 year follow up. IS included tacrolimus and sirolimus/mycophenolate. We identified episodes of irreversible S3CKD as eGFR <60 ml/min/1.73m² for ≥90d in addition to a final 12m average eGFR below threshold. We conducted multivariable competing risk (death) regression with the covariates: baseline eGFR, age at first ITx, diabetes duration, total ITx count, mean tacrolimus trough levels in year 1 post-ITx, number of acute kidney injury (AKI) events in year 1 post-ITx, sex, baseline hypertension and sirolimus exposure. We identified 199 adults (41% M followed for a median 76.1m [IQR 38.0-131.6]), of which 47.7% progressed to S3CKD within a median 28m [IQR 9-57]. Female sex and more AKI events substantially increased the risk of progression to S3CKD (HR 1.50, [95% CI 1.31,1.80, p =0.004; HR 1.21, [95% CI 1.02, 1.45, p=0.028] respectively). Older age at first-ITx, lower baseline eGFR and longer diabetes duration had modest effect of significance on the risk of progression. Mean tacrolimus level in the first year post-ITx, number of ITx, baseline hypertension and exposure to sirolimus were not significant predictors for the risk of progression to S3CKD. No sex differences were found in risk for Stage 4 or 5 CKD. IS may put female ITx recipients at greater hazard of progressing to S3CKD, independently of other potential risk factors. Further study is required to elucidate this association, which could translate into sex-specific strategies to manage IS post-ITx. Effective IS regimens without nephrotoxicity remain an important goal.