Serum albumin is the major intravascular antioxidant. Though oxidative stress plays an important role in the pathophysiology of Immunoglobulin A nephropathy (IgAN), the association between serum albumin and the progression of IgAN is not entirely understood. This retrospective cohort study of 1,352 participants with biopsy-proven IgAN determined the associations between serum albumin level and the incidence of end-stage renal disease (ESRD) using a Cox proportional hazards model. Patients were divided into three groups by tertiles of serum albumin level: Low, Middle, and High group (3.9 g/dL, 4.0–4.3 g/dL, 4.4 g/dL, respectively). During the median 5.1-year follow-up period, 152 patients (11.2%) developed ESRD. Participants in the Low group had a 1.88-fold increased risk for ESRD compared with those in the High group after adjustment for clinical parameters, including urinary protein excretion, and pathological parameters (Oxford classification). We also experimentally proved the antioxidant capacity of albumin on mesangial cells. The intracellular reactive oxygen species and mitochondrial injury, induced by hydrogen peroxide were significantly attenuated in albumin-pretreated mouse mesangial cells and human kidney cells compared with γ-globulin-pretreated cells. Low serum albumin level is an independent risk factor for ESRD in patients with IgAN. The mechanism could be explained by the antioxidant capacity of serum albumin.
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