ALICE L.J. CARR, BRAULIO A. MARFIL-GARZA, ANNA LAM, BLAIRE L. ANDERSON, DOUG O'GORMAN, TATSUYA KIN, DAVID BIGAM, A.M. JAMES SHAPIRO, PETER A. SENIOR
{"title":"336-OR: 女性接受胰岛移植手术并接受基于 CNI 的免疫抑制可能会增加肾功能衰退的风险","authors":"ALICE L.J. CARR, BRAULIO A. MARFIL-GARZA, ANNA LAM, BLAIRE L. ANDERSON, DOUG O'GORMAN, TATSUYA KIN, DAVID BIGAM, A.M. JAMES SHAPIRO, PETER A. SENIOR","doi":"10.2337/db24-336-or","DOIUrl":null,"url":null,"abstract":"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. Disclosure A.L.J. Carr: None. B.A. Marfil-Garza: None. A. Lam: None. B.L. Anderson: None. D. O'Gorman: None. T. Kin: None. D. Bigam: None. A. Shapiro: Consultant; Vertex Pharmaceuticals Incorporated, Betalin Therapeutics, Hemostemix Inc, ViaCyte, Inc., Aspect Biosystems. P.A. Senior: Consultant; Abbott, Bayer Inc., Dexcom, Inc., Eli Lilly and Company, GlaxoSmithKline plc, Insulet Corporation, Novo Nordisk Canada Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Speaker's Bureau; Abbott, Dexcom, Inc., Insulet Corporation, Novo Nordisk Canada Inc. Research Support; Novo Nordisk Canada Inc.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":6.2000,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"336-OR: Females Undergoing Islet Transplantation with CNI-Based Immunosuppression May Be at Higher Risk of Renal Function Decline\",\"authors\":\"ALICE L.J. CARR, BRAULIO A. MARFIL-GARZA, ANNA LAM, BLAIRE L. ANDERSON, DOUG O'GORMAN, TATSUYA KIN, DAVID BIGAM, A.M. JAMES SHAPIRO, PETER A. SENIOR\",\"doi\":\"10.2337/db24-336-or\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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. Disclosure A.L.J. Carr: None. B.A. Marfil-Garza: None. A. Lam: None. B.L. Anderson: None. D. O'Gorman: None. T. Kin: None. D. Bigam: None. A. Shapiro: Consultant; Vertex Pharmaceuticals Incorporated, Betalin Therapeutics, Hemostemix Inc, ViaCyte, Inc., Aspect Biosystems. P.A. 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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. Disclosure A.L.J. Carr: None. B.A. Marfil-Garza: None. A. Lam: None. B.L. Anderson: None. D. O'Gorman: None. T. Kin: None. D. Bigam: None. A. Shapiro: Consultant; Vertex Pharmaceuticals Incorporated, Betalin Therapeutics, Hemostemix Inc, ViaCyte, Inc., Aspect Biosystems. P.A. Senior: Consultant; Abbott, Bayer Inc., Dexcom, Inc., Eli Lilly and Company, GlaxoSmithKline plc, Insulet Corporation, Novo Nordisk Canada Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Speaker's Bureau; Abbott, Dexcom, Inc., Insulet Corporation, Novo Nordisk Canada Inc. Research Support; Novo Nordisk Canada Inc.
期刊介绍:
Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes.
However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.