α1-acid glycoprotein attenuates adriamycin-induced nephropathy via CD163 expressing macrophages induction

Background: Recent clinical studies have shown that proteinuria is a critical factor in the progression of chronic kidney disease (CKD) and onset of cardiovascular disease (CVD). Inflammation and infiltration of macrophages into renal tissue are implicated as a cause of proteinuria. α1-acid glycoprotein (AGP), an acute phase plasma protein, is leaked into the urine in the patients with proteinuria. However, the relationship among the urinary leakage of AGP, renal inflammation and proteinuria remains unclear. Methods: Human AGP (hAGP) was exogenously administrated for five consecutive days to adriamycin-induced nephropathy model mice. Results: Adriamycin treatment increased urinary AGP accompanied by decreasing plasma AGP in mice. Exogenous hAGP administration to adriamycin-treated mice suppressed proteinuria, renal histological injury and inflammation. Then, hAGP administration increased renal CD163 expression, a marker of anti-inflammatory macrophages. Similar changes was observed in phorbol 12-myristate 13-acetate-differentiated THP-1 cells treated with hAGP. Even in the presence of lipopolysaccharide, hAGP treatment increased CD163/IL-10 expression in differentiated THP-1 cells. Conclusions: AGP alleviates proteinuria and renal injury in mice with proteinuric kidney disease via induction of CD163-expressing macrophages with anti-inflammatory function. The results demonstrate that endogenous AGP could work to protect against glomerulus disease. Thus, AGP supplementation could be a possible new therapeutic intervention for patients with glomerular disease.