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

IF 6.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes Pub Date : 2024-07-19 DOI:10.2337/db24-336-or
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
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引用次数: 0

摘要

胰岛移植(ITx)是治疗 1 型糖尿病患者反复发作的严重低血糖症的一种成熟疗法,但需要终身免疫抑制(IS),而免疫抑制可能具有肾毒性。我们进行了一项风险回归研究,以确定与 ITx 后发展为 3 期或更严重的 CKD(S3CKD)相关的因素。我们使用的数据来自 1999 年 3 月 11 日至 2019 年 10 月 1 日期间在阿尔伯塔大学医院接受单纯 ITx 并随访 1 年的成人。IS包括他克莫司和西罗莫司/霉酚酸酯。我们将不可逆的 S3CKD 识别为 eGFR <60 ml/min/1.73m2 ≥90d,以及最终 12m 平均 eGFR 低于阈值。我们对以下协变量进行了多变量竞争风险(死亡)回归:基线 eGFR、首次 ITx 年龄、糖尿病持续时间、ITx 总次数、ITx 后第 1 年他克莫司平均谷值、ITx 后第 1 年急性肾损伤 (AKI) 事件次数、性别、基线高血压和西罗莫司暴露。我们确定了 199 名成人(41% 为男性,随访时间中位数为 76.1m [IQR 38.0-131.6]),其中 47.7% 在中位数 28m [IQR 9-57] 内发展为 S3CKD。女性性别和更多的 AKI 事件大大增加了进展为 S3CKD 的风险(分别为 HR 1.50 [95% CI 1.31,1.80,p=0.004;HR 1.21 [95% CI 1.02,1.45,p=0.028])。首次进行 ITx 时年龄较大、基线 eGFR 较低和糖尿病病程较长对病情进展风险的显著性影响不大。ITx后第一年的平均他克莫司水平、ITx次数、基线高血压和西罗莫司暴露对进展为S3CKD的风险无显著预测作用。4期或5期CKD的风险没有性别差异。除其他潜在风险因素外,IS可能会使女性ITx接受者更容易发展为S3CKD。需要进一步研究来阐明这种关联,从而制定出针对不同性别的策略来管理 ITx 后的 IS。无肾毒性的有效 IS 方案仍是我们的重要目标。披露 A.L.J. Carr:无。B.A. Marfil-Garza: 无。A. Lam:无:无。B.L. Anderson:无。D. O'Gorman: None.T. Kin:无。D. Bigam:无。A. Shapiro:顾问;Vertex Pharmaceuticals Incorporated、Betalin Therapeutics、Hemostemix Inc、ViaCyte, Inc.、Aspect Biosystems。P.A. Senior:顾问;雅培公司、拜耳公司、Dexcom 公司、礼来公司、葛兰素史克公司、Insulet 公司、诺和诺德加拿大公司、赛诺菲公司、Vertex 制药公司。发言人办公室;雅培公司、Dexcom 公司、Insulet 公司、诺和诺德加拿大公司。研究支持;诺和诺德加拿大公司(Novo Nordisk Canada Inc.
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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.
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来源期刊
Diabetes
Diabetes 医学-内分泌学与代谢
CiteScore
12.50
自引率
2.60%
发文量
1968
审稿时长
1 months
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.
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