Oxidative stress, macrophage infiltration and CD163 expression are determinants of long-term renal outcome in macrohematuria-induced acute kidney injury of IgA nephropathy.

ABSTRACT

BACKGROUND: Macroscopic hematuria (MH) may cause acute kidney injury (AKI) in IgA nephropathy. Up to 25% of patients with MH-associated AKI do not recover baseline renal function. Our objective was to identify subjects at high risk for an adverse renal function. METHODS: We examined macrophages, oxidative stress markers (NADPH-p22 and HO-1) and the hemoglobin scavenger receptor (CD163) in renal biopsy specimens from 33 MH-AKI patients with complete recovery (CR, n = 17) or incomplete recovery (IR, n = 16) of renal function after 6.72 (range 0.5-21.5) years of follow-up. RESULTS: CD163-expressing macrophages, HO-1 and NADPH-p22 expression were located in areas surrounding tubules with iron deposits and filled with erythrocyte casts. CD163-positive macrophages score and HO-1- and p22-positive staining correlated positively with percentage of tubules with erythrocyte casts and tubular necrosis. Macrophage infiltration, CD163-positive macrophage score, NADPH-p22- and HO-1-positive staining areas were significantly greater in IR patients when compared with CR patients. The CD163-positive macrophage score and oxidative stress markers (p22 and HO-1) were negatively correlated with renal function outcome, as determined by estimated glomerular filtration rate (eGFR) and proteinuria, at the end of the follow-up period. In multivariate analysis, the CD163-positive macrophage score remained significantly associated with final eGFR and proteinuria after adjustment by age, gender, duration of MH, initial eGFR and proteinuria. CONCLUSIONS: Increased macrophage infiltration, CD163 expression and oxidative stress are significant prognostic factors for an IR of renal function in patients with MH-associated AKI. These molecular pathways may be involved in the renal response to injury and could be useful to improve diagnosis and therapeutics.