Association of amino acids related to urea cycle with risk of diabetic nephropathy in two independent cross-sectional studies of Chinese adults

OBJECTIVE: To investigate the association between amino acids related to the urea cycle and diabetic nephropathy (DN) in two independent cross-sectional studies. METHODS: We obtained the medical records of 145 individuals with DN and 596 individuals without DN who attended an annual health examination at Liaoning Medical University First Affiliated Hospital (LMUFAH), China, from May 2015 to August 2016. From April 2018 to April 2019, we collected medical records of another 741 individuals: 338 individuals with DN and 403 individuals without DN from the Second Affiliated Hospital of Dalian Medical University (DALIAN), China. Binary logistic regression was used to obtain the odds ratio (OR) and 95% confidence interval (CI). RESULTS: In two independent cross-sectional studies, we observed that citrulline was consistently associated with DN risk [OR (95% CI) of per standard deviation (SD) increase for citrulline in the LMUFAH population: 1.200 (1.006, 1.432); OR (95% CI) of per SD increase for citrulline in the DALIAN population: 1.189 (1.012, 1.396); pooled effect size for citrulline: 1.194 (1.060, 1.345)]. However, ornithine, arginine, and the ratio of arginine to ornithine were consistently unrelated to DN risk, and the ratios of other amino acids in the urea cycle were inconsistently associated with DN risk. CONCLUSIONS: Citrulline was consistently associated with DN risk in two independent cross-sectional studies in Chinese adults.