The American journal of clinical nutrition · 2025
Circulating bile acids, bile acid receptor polymorphisms, and risk of chronic kidney disease among individuals with newly diagnosed type 2 diabetes: a prospective study.
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Zhu Kai, Li Rui, Qiu Zixin, Yu Hancheng, Xu Kun, Li Ruyi, Li Lin, Cheng Xu, He Meian, Geng Tingting, Tang Huiru, Pan An, Liu Gang
Аннотация
BACKGROUND: Bile acids (BAs), synthesized in the liver as primary BAs (PBAs) and converted by gut microbiota into secondary BAs (SBAs), are implicated in renal health. Diet could influence gut microbiome and BA levels.
OBJECTIVES: We aimed to prospectively investigate the associations of circulating BA and their receptor polymorphisms (e.g., nuclear farnesoid X receptor [FXR]) with chronic kidney disease (CKD) risk in individuals with T2D.
METHODS: This study included 729 participants with newly diagnosed T2D without prevalent CKD from the Dongfeng-Tongji Cohort study in China. Circulating concentrations of BA subtypes, including PBAs and SBAs in both unconjugated and conjugated forms, were measured via liquid chromatography-tandem mass spectrometry.
RESULTS: During the 5-y follow-up, 113 incident cases of CKD were documented. Higher concentrations of most PBA species and total unconjugated SBAs were significantly associated with higher risks of incident CKD. The odds ratios (95% CIs) of CKD comparing the highest with the lowest tertile were 2.54 (95% CI: 1.47, 4.39) for chenodeoxycholate, 3.04 (95% CI: 1.69, 5.47) for glycocholate, 2.78 (95% CI: 1.58, 4.88) for glycochenodeoxycholate, 2.12 (95% CI: 1.23, 3.63) for taurochenodeoxycholate, 2.63 (95% CI: 1.52, 4.54) for total unconjugated PBAs, 2.48 (95% CI: 1.40, 4.39) for total conjugated PBAs, and 2.17 (95% CI: 1.27, 3.71) for total unconjugated SBAs (all P-trend < 0.05). Restricted cubic spline analysis showed linear relationships between chenodeoxycholate, glycocholate, glycochenodeoxycholate, taurochenodeoxycholate, and total unconjugated PBAs, conjugated PBAs, and unconjugated SBAs and risk of CKD. Additionally, a total of 3 single-nucleotide polymorphisms in FXR (rs2025801, rs56163822, and rs17030295) were significantly associated with CKD risk; and significant multiplicative interactions were found between these single-nucleotide polymorphisms and unconjugated SBAs.
CONCLUSIONS: Among adults with T2D, higher concentrations of most circulating PBAs and total unconjugated SBAs are linearly associated with higher risk of CKD, and genetic variations in FXR modify the association of unconjugated SBAs with CKD.
OBJECTIVES: We aimed to prospectively investigate the associations of circulating BA and their receptor polymorphisms (e.g., nuclear farnesoid X receptor [FXR]) with chronic kidney disease (CKD) risk in individuals with T2D.
METHODS: This study included 729 participants with newly diagnosed T2D without prevalent CKD from the Dongfeng-Tongji Cohort study in China. Circulating concentrations of BA subtypes, including PBAs and SBAs in both unconjugated and conjugated forms, were measured via liquid chromatography-tandem mass spectrometry.
RESULTS: During the 5-y follow-up, 113 incident cases of CKD were documented. Higher concentrations of most PBA species and total unconjugated SBAs were significantly associated with higher risks of incident CKD. The odds ratios (95% CIs) of CKD comparing the highest with the lowest tertile were 2.54 (95% CI: 1.47, 4.39) for chenodeoxycholate, 3.04 (95% CI: 1.69, 5.47) for glycocholate, 2.78 (95% CI: 1.58, 4.88) for glycochenodeoxycholate, 2.12 (95% CI: 1.23, 3.63) for taurochenodeoxycholate, 2.63 (95% CI: 1.52, 4.54) for total unconjugated PBAs, 2.48 (95% CI: 1.40, 4.39) for total conjugated PBAs, and 2.17 (95% CI: 1.27, 3.71) for total unconjugated SBAs (all P-trend < 0.05). Restricted cubic spline analysis showed linear relationships between chenodeoxycholate, glycocholate, glycochenodeoxycholate, taurochenodeoxycholate, and total unconjugated PBAs, conjugated PBAs, and unconjugated SBAs and risk of CKD. Additionally, a total of 3 single-nucleotide polymorphisms in FXR (rs2025801, rs56163822, and rs17030295) were significantly associated with CKD risk; and significant multiplicative interactions were found between these single-nucleotide polymorphisms and unconjugated SBAs.
CONCLUSIONS: Among adults with T2D, higher concentrations of most circulating PBAs and total unconjugated SBAs are linearly associated with higher risk of CKD, and genetic variations in FXR modify the association of unconjugated SBAs with CKD.