肥胖与慢性肾脏病的关联：基于减肥手术队列的多变量孟德尔随机化分析和观察性数据。
Association Between Obesity and Chronic Kidney Disease: Multivariable Mendelian Randomization Analysis and Observational Data From a Bariatric Surgery Cohort.
机构信息
Department of Medicine, University Health Network and University of Toronto, Toronto, Ontario, Canada.
Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
出版信息
Diabetes. 2023 Apr 1;72(4):496-510. doi: 10.2337/db22-0696.
Obesity is postulated to independently increase chronic kidney disease (CKD), even after adjusting for type 2 diabetes (T2D) and hypertension. Dysglycemia below T2D thresholds, frequently seen with obesity, also increases CKD risk. Whether obesity increases CKD independent of dysglycemia and hypertension is unknown and likely influences the optimal weight loss (WL) needed to reduce CKD. T2D remission rates plateau with 20-25% WL after bariatric surgery (BS), but further WL increases normoglycemia and normotension. We undertook bidirectional inverse variance weighted Mendelian randomization (IVWMR) to investigate potential independent causal associations between increased BMI and estimated glomerular filtration rate (eGFR) in CKD (CKDeGFR) (<60 mL/min/1.73 m2) and microalbuminuria (MA). In 5,337 BS patients, we assessed whether WL influences >50% decline in eGFR (primary outcome) or CKD hospitalization (secondary outcome), using <20% WL as a comparator. IVWMR results suggest that increased BMI increases CKDeGFR (b = 0.13, P = 1.64 × 10-4; odds ratio [OR] 1.14 [95% CI 1.07, 1.23]) and MA (b = 0.25; P = 2.14 × 10-4; OR 1.29 [1.13, 1.48]). After adjusting for hypertension and fasting glucose, increased BMI did not significantly increase CKDeGFR (b = -0.02; P = 0.72; OR 0.98 [0.87, 1.1]) or MA (b = 0.19; P = 0.08; OR 1.21 [0.98, 1.51]). Post-BS WL significantly reduced the primary outcome with 30 to <40% WL (hazard ratio [HR] 0.53 [95% CI 0.32, 0.87]) but not 20 to <30% WL (HR 0.72 [0.44, 1.2]) and ≥40% WL (HR 0.73 [0.41, 1.30]). For CKD hospitalization, progressive reduction was seen with increased WL, which was significant for 30 to <40% WL (HR 0.37 [0.17, 0.82]) and ≥40% WL (HR 0.24 [0.07, 0.89]) but not 20 to <30% WL (HR 0.60 [0.29, 1.23]). The data suggest that obesity is likely not an independent cause of CKD. WL thresholds previously associated with normotension and normoglycemia, likely causal mediators, may reduce CKD after BS.
肥胖症被认为即使在调整了 2 型糖尿病（T2D）和高血压因素后，也会独立增加慢性肾脏病（CKD）的发生风险。肥胖症常伴有血糖异常，但低于 T2D 阈值，也会增加 CKD 风险。肥胖症是否会独立于血糖异常和高血压增加 CKD 尚不清楚，这可能会影响到降低 CKD 所需的最佳减重（WL）效果。减重手术后（BS），体重减轻 20-25% 后 T2D 缓解率达到平台期，但进一步 WL 会增加正常血糖和正常血压。我们进行了双向逆方差加权孟德尔随机化（IVWMR），以研究 CKD（CKDeGFR）（<60 mL/min/1.73 m2）和微量白蛋白尿（MA）中 BMI 增加与估计肾小球滤过率（eGFR）之间潜在的独立因果关系。在 5337 名 BS 患者中，我们使用<20% WL 作为比较，评估 WL 是否会影响 eGFR 下降>50%（主要结局）或 CKD 住院（次要结局）。IVWMR 结果表明，BMI 增加会增加 CKDeGFR（b = 0.13，P = 1.64×10-4；OR 1.14[1.07，1.23]）和 MA（b = 0.25；P = 2.14×10-4；OR 1.29[1.13，1.48]）。在调整了高血压和空腹血糖后，BMI 增加与 CKDeGFR（b = -0.02；P = 0.72；OR 0.98[0.87，1.1]）或 MA（b = 0.19；P = 0.08；OR 1.21[0.98，1.51]）均无显著相关性。BS 后 WL 显著降低了主要结局，其中 30-<40% WL 时（HR 0.53[95%CI 0.32，0.87]），但 20-<30% WL 时（HR 0.72[0.44，1.2]）和≥40% WL 时（HR 0.73[0.41，1.30]）没有显著降低。对于 CKD 住院，随着 WL 的增加，逐渐减少，其中 30-<40% WL 时（HR 0.37[0.17，0.82]）和≥40% WL 时（HR 0.24[0.07，0.89]）有显著相关性，但 20-<30% WL 时（HR 0.60[0.29，1.23]）没有显著相关性。数据表明肥胖症可能不是 CKD 的独立原因。先前与正常血压和正常血糖相关的 WL 阈值，可能是因果中介，可能会降低 BS 后 CKD 的发生风险。
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