Circulating bile acids up risk of CKD in adults with T2D

Higher concentrations of most circulating primary bile acids (PBAs) and total secondary BAs (SBAs) appear to increase the risk of chronic kidney disease (CKD) among adults with type 2 diabetes (T2D), suggests a study.

Moreover, genetic variations in farnesoid X receptor (FXR) modify the relationship between unconjugated SBAs and CKD.

A total of 729 participants with newly diagnosed T2D without prevalent CKD from the Dongfeng-Tongji Cohort study in China were included in this study. The authors used liquid chromatography‒tandem mass spectrometry to measure circulating concentrations of BA subtypes, such as PBAs and SBAs in both unconjugated and conjugated forms.

Some 113 incident cases of CKD were recorded over 5 years of follow-up. Higher concentrations of most PBA species and total unconjugated SBAs significantly correlated with increased risks of incident CKD.

Comparing the highest with the lowest tertile, the odds ratios of CKD were 2.54 (95 percent confidence interval [CI], 1.47‒4.39) for chenodeoxycholate, 3.04 (95 percent CI, 1.69‒5.47) for glycocholate, 2.78 (95 percent CI, 1.58‒4.88) for glycochenodeoxycholate, 2.12 (95 percent CI, 1.23‒3.63) for taurochenodeoxycholate, 2.63 (95 percent CI, 1.52‒4.54) for total unconjugated PBAs, 2.48 (95 percent CI, 1.40‒4.38) for total conjugated PBAs, and 2.17 (95 percent CI, 1.27‒3.71) for total unconjugated SBAs (p_trend<0.05 for all).

In restricted cubic spline analysis, the risk of CKD showed linear associations with chenodeoxycholate, glycocholate, glycochenodeoxycholate, taurochenodeoxycholate, and total unconjugated PBAs, conjugated PBAs, and unconjugated SBAs.

Furthermore, three single-nucleotide polymorphisms in FXR (rs2025801, rs56163822, and rs17030295) showed a significant association with the risk of CKD. Significant multiplicative interactions were observed between these polymorphisms and unconjugated SBAs.