Association of redox and inflammation-related biomarkers with prognosis in IgA nephropathy: A prospective observational study

Abstract

Background: IgA nephropathy (IGAN) has a variable prognosis. Risk stratification tools are usually based on clinical parameters combined with histologic Oxford-MEST-C score. Circulating redox- and inflammation-related biomarkers may be related to histological changes in IGAN. Therefore, we studied the performance of these biomarkers in predicting the rate of GFR-loss in IGAN.

Methods: This was an observational prospective study. Fifty-seven stable patients with IGAN were examined at baseline and after a mean observational time of 5.9 ± 1.1 years. The main outcome measure was eGFR-loss per year with predefined groups, stable (<1.5 ml/min/1,73 m²/year, intermediate (between 1.5 and 2.5), and progressive (>2.5).

Results: Fifteen patients were in the progressive, 11 in the intermediate, and 31 in the stable groups. Positive relationships were detected between eGFR-loss per year and baseline nitrate, oxidized free cysteine, parathyroid hormone, APRIL, TNFR1, CD30, chitinase 3, and LIF-5. The progressive group had elevated concentrations of these markers plus AOPP and osteopontin. Through ROC analysis, it was observed that AOPP, oxidized free cysteine, TNFR1, osteopontin, and LIF-5 had the best ability to identify progressive vs. non-progressive diseases. The combination of urinary albumin/creatinine ratio with AOPP and TNFR1 significantly improved the ability to identify progressive eGFR decline with ROC AUC 95% (adjusted 85%).

Conclusions: We found prognostic biomarkers related to the rate of eGFR-loss in IGAN. These biomarkers may help identify patients at risk of progressive disease. AOPP, oxidized free cysteine, TNFR1, and osteopontin are promising prognostic biomarkers in IGAN, however, further validation studies are needed.

Keywords: Biomarkers; IgA nephropathy; Inflammation; Oxidative stress; Prognosis.