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

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.