Liu Ke, Yang Qing, Lang Yanlin, Zou Yutong, Yuan Jiamin, Yang Jia, Ma Jing, Cai Linli, Kong Xianglin, Yang Fuhai, Liu Fang
Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China.
Laboratory of Diabetic Kidney Disease, Kidney Research Institute, Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China.
J Diabetes. 2025 Aug;17(8):e70140. doi: 10.1111/1753-0407.70140.
This study aims to explore the effect of the ketogenic diet (KD) on the occurrence of end-stage renal disease (ESRD) and the longitudinal relationship between circulating β-hydroxybutyrate (β-OHB) and kidney outcomes.
We used the dietary ketogenic ratio (DKR) to estimate the nutritional ketosis probability of KD and analyzed the association with ESRD using NHANES cross-sectional data by Spearman correlation coefficient and multivariate logistic regression model. We also used the Kaplan-Meier method, Cox regression analysis, and restricted cubic splines (RCS) to analyze the relationship between circulating β-OHB and renal outcomes in the T2DM-DKD longitudinal cohort of West China Hospital. Mendelian randomization (MR) was also employed to evaluate potential causal associations.
The cross-sectional analysis revealed that non-ESRD patients had significantly higher baseline age, BMI, serum albumin, and DKR values, with a weak negative correlation between DKR and serum creatinine (ρ = -0.072, p = 0.011). Logistic regression consistently indicated a reduced ESRD prevalence in higher DKR quartiles. In the longitudinal study, elevated β-OHB levels were associated with improved renal survival and a lower risk of ESRD, with RCS analysis identifying the lowest risk at approximately 0.25 mmol/L. MR analyses supported these findings, showing inverse correlations between genetically predicted β-OHB and creatinine (p = 0.007) and cystatin c (p < 0.001).
These findings suggest that KD may be associated with a lower incidence of ESRD in DKD patients, with elevated β-OHB levels independently associated with a reduced risk of ESRD, warranting further research to confirm causality and elucidate underlying mechanisms.
本研究旨在探讨生酮饮食（KD）对终末期肾病（ESRD）发生的影响以及循环β-羟基丁酸（β-OHB）与肾脏结局之间的纵向关系。
我们使用饮食生酮比（DKR）来估计KD的营养性酮症发生概率，并通过Spearman相关系数和多变量逻辑回归模型，利用美国国家健康与营养检查调查（NHANES）的横断面数据分析其与ESRD的关联。我们还使用Kaplan-Meier法、Cox回归分析和限制性立方样条（RCS）来分析华西医院2型糖尿病-糖尿病肾病（T2DM-DKD）纵向队列中循环β-OHB与肾脏结局之间的关系。还采用了孟德尔随机化（MR）来评估潜在的因果关联。
横断面分析显示，非ESRD患者的基线年龄、体重指数、血清白蛋白和DKR值显著更高，DKR与血清肌酐之间呈弱负相关（ρ = -0.072，p = 0.011）。逻辑回归一致表明，在较高DKR四分位数中ESRD患病率降低。在纵向研究中，β-OHB水平升高与肾脏存活率提高和ESRD风险降低相关，RCS分析确定在约0.25 mmol/L时风险最低。MR分析支持了这些发现，显示基因预测的β-OHB与肌酐（p = 0.007）和胱抑素C（p < 0.001）之间呈负相关。
这些发现表明，KD可能与DKD患者中较低的ESRD发病率相关，β-OHB水平升高与ESRD风险降低独立相关，需要进一步研究以确认因果关系并阐明潜在机制。
