CKD Risk Prediction among Obese Living Kidney Donors

肥胖活体肾捐献者的 CKD 风险预测

• 批准号: 10302301
• 负责人: JAYME ELIZABETH LOCKE
• 金额: $ 67.53万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10302301
• 关键词: Address; Age; Body Weight decreased; Body mass index; Caring; Characteristics; Cohort Studies; Data; Data Sources; Disease; Donor Selection; End stage renal failure; Equilibrium; Ethnic Origin; Family; Funding; General Population; Health; Incidence; Individual; Informed Consent; Kidney; Kidney Failure; Left; Living Donors; Living Wills; Longitudinal cohort study; Medical; Medical Records; Metabolic syndrome; Methods; Modification; Nephrons; Non obese; Obesity; Organ; Outcome; Phenotype; Questionnaires; Recording of previous events; Relaxation; Retrospective cohort study; Risk; Risk Estimate; Risk Factors; Safety; Selection Criteria; Source; Time; Transplantation; United States; United States National Institutes of Health; Update; Weight; Weight Gain; base; cohort; comorbidity; falls; fasting glucose; hazard; high risk; living kidney donor; novel; obese person; obesity risk; outcome prediction; personalized approach; predictive tools; prognostic; response; risk prediction; tool; transplant centers

SUMMARY Living kidney donors continue to be a critical source of organs facilitating timely transplantation and excellent outcomes. Historically, living donors were healthy and free of baseline abnormalities. In response to the organ shortage, transplant centers now commonly approve donors classified as obese (body mass index (BMI) ≥ 30kg/m2), and currently, more than 25% of all living donors are considered obese at donation. Relaxation of selection criteria to include obese living donors has occurred despite a paucity of safety data. Determining candidacy for living donation among obese individuals remains challenging, as the appropriate BMI cutoff above which donation is no longer safe is unknown. Most centers have implemented a “one size fits all” approach to setting BMI limits (e.g. individuals with BMI > 35kg/m2 are excluded from donation) rather than a personalized approach that accounts for individual baseline differences. In the general population, obese individuals have a 3.57-fold higher risk for ESRD compared to individuals with normal weight (BMI 18.5-24.9 kg/m2). Donors are not drawn from the general population, but are very carefully screened, and the impact of obesity might be different in these healthier individuals. In a recent multi-cohort study of individuals healthy enough to be potential donors (healthy non-donors), the adjusted risk for ESRD associated with obesity was only 1.16-fold higher but varied significantly based on other baseline comorbidities. The true risk among obese living donors likely falls somewhere in between these estimates: obese living donors are otherwise healthy at baseline but lose half their nephron mass. Our preliminary findings suggest that risk for post-donation ESRD is significantly higher among obese compared with non-obese donors. However, it remains unclear if this risk is modified by other baseline comorbidities or obesity-related characteristics (e.g. BMI trajectory, metabolic syndrome), reflective of underlying differences between obese and non-obese persons, or directly attributable to donation itself. We hypothesize that the impact of obesity on post-donation ESRD risk varies significantly by obesity-related characteristics and other comorbidities, and an obese phenotype exists in whom living kidney donation is safe. To better understand the relationship between obesity and risk for post-donation kidney failure, we will leverage and build upon an existing NIH-funded retrospective cohort study of live donors to assemble the largest cohort of obese living donors and will: (1) explore the association of baseline health characteristics with risk for post-donation kidney failure among obese living kidney donors; (2) explore the association of obesity-specific risk factors with risk for post-donation kidney failure; (3) develop a tool for kidney failure risk among obese living donors; (4) estimate risk for post-donation kidney failure among obese living donors directly attributable to donation. Our findings will have a major impact on the practice of living donation among obese persons, informing critical aspects of donor selection, informed consent, and post-donation care.

总结 活体肾脏捐献者仍然是促进及时移植的器官的重要来源， 结果。从历史上看，活体供体是健康的，没有基线异常。在回应器官 短缺，移植中心现在通常批准捐赠者被归类为肥胖（体重指数（BMI）≥ 目前，超过25%的活体捐赠者在捐赠时被认为肥胖。放宽 尽管缺乏安全性数据，但已经出现了包括肥胖活体供体的选择标准。确定 肥胖者活体捐献的候选资格仍然具有挑战性，因为适当的BMI临界值 超过这个值捐献就不安全了。大多数中心都实行了“一刀切” 设定BMI限值的方法（例如，BMI > 35 kg/m2的个体被排除在捐赠之外），而不是 个性化的方法，考虑到个人的基线差异。在一般人群中，肥胖 与正常体重的个体相比，个体患ESRD的风险高3.57倍（BMI 18.5-24.9 kg/m2）。捐助者不是从普通民众中挑选的，而是经过非常仔细的筛选， 肥胖在这些健康的个体中可能是不同的。在最近的一项针对健康个体的多队列研究中， 足够成为潜在的供体（健康的非供体），与肥胖相关的ESRD的校正风险为 仅高1.16倍，但基于其他基线合并症而显著变化。肥胖人群的真正风险 活体捐赠者可能福尔斯这些估计值之间：肥胖的活体捐赠者在其他方面都很健康， 但失去一半的肾单位质量。我们的初步研究结果表明，捐赠后终末期肾病的风险是 在肥胖者中显著高于非肥胖者。然而，目前尚不清楚这种风险是否 通过其他基线合并症或肥胖相关特征（例如BMI轨迹、代谢 综合征），反映肥胖和非肥胖者之间的潜在差异，或直接归因于 捐赠自己。我们假设肥胖对捐献后终末期肾病风险的影响在以下方面存在显著差异： 肥胖相关的特征和其他合并症，以及存在肥胖表型的患者， 捐赠是安全的。为了更好地了解肥胖与肾脏捐赠风险之间的关系， 失败，我们将利用和建立在现有的NIH资助的回顾性队列研究的活供体， 收集最大的肥胖活体捐赠者队列，并将：（1）探索基线健康与 肥胖活体供肾者的供后肾衰竭风险特征;（2）探讨肥胖活体供肾者的 肥胖特异性风险因素与捐赠后肾衰竭风险的关联;（3）开发肾脏评估工具， 肥胖活体供肾者的肾衰竭风险;（4）估计肥胖活体供肾者的肾衰竭风险 捐赠者直接捐赠。我们的研究结果将对活体捐赠的实践产生重大影响 在肥胖者中，告知捐赠者选择、知情同意和捐赠后护理的关键方面。

项目成果

Hepatic macrosteatosis in the US pediatric deceased liver donor population.

• DOI: 10.1111/petr.14155
• 发表时间: 2022-03
• 期刊: Pediatric transplantation
• 影响因子: 1.3
• 作者: Purvis JW;Orandi BJ;Dhall D;McLeod C;Gutierrez Sanchez LH;Gray M;Frey K;Sheikh SS;Cannon RM;Terrault NA;Lewis CE;Locke JE
• 通讯作者: Locke JE

Increasing Obesity Prevalence in the United States End-Stage Renal Disease Population

美国终末期肾病人群肥胖患病率不断上升

• 发表时间: 2020
• 作者: B. Shelton

Perpetuating Disparity: Failure of the Kidney Transplant System to Provide the Most Kidney Transplants to Communities With the Greatest Need.

永久差异：肾脏移植系统失败，无法向最需要的社区提供最多的肾脏移植。

• DOI: 10.1097/sla.0000000000005585
• 发表时间: 2022-10-01
• 期刊: Annals of surgery
• 影响因子: 9

Impact of refitted race-free eGFR formula on obesity pharmacotherapy options.

• DOI: 10.1002/oby.23542
• 发表时间: 2022-11
• 期刊: Obesity (Silver Spring, Md.)

Reclassification of CKD in living kidney donors with the refitted race-free eGFR formula.

使用改良的无种族 eGFR 公式对活体肾捐献者的 CKD 进行重新分类。

• DOI: 10.1016/j.amjsurg.2022.09.024
• 发表时间: 2023
• 期刊: American journal of surgery
• 影响因子: 3
• 作者: Orandi,BabakJ;Kumar,Vineeta;Reed,RhiannonD;MacLennan,PaulA;Shelton,BrittanyA;McLeod,Chandler;Locke,JaymeE
• 通讯作者: Locke,JaymeE