The redox state of human serum albumin (HSA) has attracted interest as a possible biomarker for oxidative stress (OS) in humans. Although previous studies on this topic have taken only clinical settings into consideration, evidence of its efficacy in nonclinical settings remains to be established. The present study aimed to examine and validate the relationship between HSA redox state and renal function in a rural Japanese population. We analyzed two independent data sets from health checkup programs conducted in 2013 and 2016: one for discovery ( n = 267) and the other for replication ( n = 367). The fraction of human mercaptalbumin (HMA) to total HSA [f(HMA)] was determined using our revised method of high-performance liquid chromatography with post-column bromocresol green. The estimated glomerular filtration rate (eGFR) was calculated based on each individual's serum creatinine value, sex, and age. Adjustment for potential confounders revealed positive associations of fraction of human mercaptalbumin [f(HMA)] with eGFR in the discovery and replication analyses ( P < 0.001 and P = 0.03, respectively). Multivariate logistic regression analyses demonstrated significant inverse associations between renal dysfunction (defined as eGFR < 60 ml·min-1·1.73 m-2) and f(HMA) by a factor of 0.50 and 0.65 (confidence intervals of 0.26-0.91 and 0.37-1.00), respectively, with a unit of 10% f(HMA). Our results indicate that HSA redox state is consistently associated with renal dysfunction in both clinical and nonclinical settings.
Keywords: human serum albumin; oxidative stress; redox state; renal dysfunction.