Norcholic acid: a novel biomarker of early kidney injury in patients with metabolic dysfunction-associated fatty liver disease

Abstract

Background Bile acids (BAs) are signaling molecules that regulate numerous metabolic processes in metabolic dysfunction-associated (MAFLD) and chronic kidney disease (CKD). Whether BAs are also associated with early abnormalities in renal function in MAFLD is uncertain.Methods We quantitatively measured plasma BA concentrations in biopsy-proven MAFLD patients with or without abnormal albuminuria (defined as albumin-to-creatinine ratio ≥ 30 mg/g) and in healthy controls, by using ultraperformance liquid chromatography coupled to tandem mass spectrometry.Results Plasma BA profiles (conjugated BAs, glycine-conjugated BAs, glycine-conjugated primary BAs, total conjugated primary BAs, and glycine-conjugated primary BAs) were up-regulated in MAFLD patients with abnormal albuminuria compared to their counterparts with normal albuminuria and healthy controls. In particular, we identified a distinct individual BA, i.e., norcholic acid (NorCA) that was markedly upregulated in MAFLD patients with abnormal albuminuria, and that was also positively correlated with albuminuria. Moreover, the combination of NorCA, tauro-deoxycholic acid, tauro-lithocholic acid and cholic acid, improved identification of abnormal albuminuria in MAFLD patients in a predictive model, that also included diabetes, hypertension, body mass index, and serum alanine aminotransferase levels (AUC = 0.80, 95%CI 0.740–0.863).Conclusion BA biomarkers are increased in patients with MAFLD and abnormal albuminuria and further investigation of their role in renal function is warranted.