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 plateaus with 20-25%WL postbariatric surgery (BS) but further WL increases normoglycemia/normotension. We undertook bidirectional inverse variance weighted Mendelian randomization (IVMR) to investigate potential independent causal associations between increased BMI and CKDeGFR (estimated glomerular filtration rate, eGFR < 60 ml/min1.73m2) and microalbuminuria (MA). In 5337 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 suggests increased BMI increases CKDeGFR (beta=0.13, p=1.64x10-4), Odds ratio, OR (95% confidence interval, CI)=1.14(1.07-1.23) and MA (b=0.25, p=2.14 x 10-4,OR(95%CI)=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(95%CI)=0.98(0.87-1.1) or MA (b=0.19, p=0.08, OR (95%CI)=1.21 (0.98, 1.51). Post-BS WL significantly reduced the primary outcome with 30-<40%WL (Hazard ratio HR=0.53, 95%CI=0.32-0.87), but not 20-<30%WL (HR=0.72, 95%CI=0.44-1.2) and ≥40%WL (HR=0.73, 95%CI=0.41-1.30). For CKD hospitalization, progressive reduction was seen with increased WL which was significant for 30-<40%WL (HR=0.37, 95%CI=0.17-0.82) and ≥40%WL (HR=0.24, 95%CI=0.07-0.89), but not 20-30%WL (HR=0.60, 95%CI=0.29-1.23). The data suggests obesity is likely not an independent cause of CKD. WL thresholds previously associated with normotension and normoglycemia, likely causal mediators, may reduce CKD post-BS.

中文翻译：

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肥胖与慢性肾病之间的关联：来自减肥手术队列的多变量孟德尔随机化分析和观察数据

假设肥胖会独立增加慢性肾病 (CKD)，即使在针对 2 型糖尿病 (T2D) 和高血压进行调整后也是如此。血糖异常低于 T2D 阈值（常见于肥胖症）也会增加 CKD 风险。肥胖是否独立于血糖异常和高血压而增加 CKD 尚不清楚，并且可能影响减少 CKD 所需的最佳减重 (WL)。T2D 缓解率稳定在 20-25%WL 减肥手术后 (BS)，但进一步的 WL 会增加正常血糖/正常血压。我们采用双向逆方差加权孟德尔随机化 (IVMR) 来研究增加的 BMI 和 CKDeGFR（估计的肾小球滤过率，eGFR < 60 ml/min1.73m2）和微量白蛋白尿 (MA) 之间潜在的独立因果关系。在 5337 名 BS 患者中，我们评估了 WL 是否影响 >; 使用 <20% WL 作为比较，eGFR（主要结果）或 CKD 住院（次要结果）下降 50%。IVWMR 表明增加 BMI 会增加 CKDeGFR (beta=0.13, p=1.64x10-4)、优势比或 (95% 置信区间, CI)=1.14(1.07-1.23) 和 MA (b=0.25, p=2.14 x 10 -4,OR(95%CI)=1.29(1.13-1.48)。在调整高血压和空腹血糖后，增加的 BMI 并未显着增加 CKDeGFR (b=-0.02, p=0.72)，OR(95%CI)= 0.98(0.87-1.1) 或 MA (b=0.19, p=0.08, OR (95%CI)=1.21 (0.98, 1.51)。BS 后 WL 显着降低主要结果，30-<40%WL（危险比率 HR=0.53，95%CI=0.32-0.87），但不是 20-<30%WL（HR=0.72，95%CI=0.44-1.2）和≥40%WL（HR=0.73，95%CI= 0.41-1.30）。对于 CKD 住院治疗，随着 WL 的增加，WL 逐渐减少，这对于 30-<40%WL 是显着的（HR=0.37，95%CI=0.17-0。82) 和≥40%WL（HR=0.24，95%CI=0.07-0.89），但不是 20-30%WL（HR=0.60，95%CI=0.29-1.23）。数据表明肥胖可能不是 CKD 的独立原因。先前与正常血压和正常血糖相关的 WL 阈值可能是因果介质，可能会减少 BS 后 CKD。