Loss of NGAL protects against albumin-induced kidney inflammation and fibrosis.

Abstract

Increased albuminuria represents a risk factor for chronic kidney disease (CKD), and it is associated with the development and progression of kidney inflammation and fibrosis. The expression of neutrophil gelatinase-associated lipocalin (NGAL), a biomarker for kidney damage, is increased in CKD patients and experimental animal models of kidney damage. However, it is unknown whether NGAL is necessary for the promotion of kidney inflammation and fibrosis associated with the albumin exposition. Male C57BL6/J wild-type (WT) and NGAL (knockout) KO mice (8-12&#x2009;weeks,&#x2009;=&#x2009;5-6) were subjected to the albumin overload (AO) model (10&#x2009;mg/g/day i.p.) or Vehicle (0.9% NaCl i.p.) for 7&#x2009;days. Kidney function and inflammatory and fibrotic status in the kidney were assessed. In WT and NGAL-KO mice, AO significantly increased plasma protein (1.3-fold,&#x2009;<&#x2009;0.001) and albuminuria (5.6-fold,&#x2009;<&#x2009;0.01). In WT mice, AO induced a significant increase in F4/80-positive kidney macrophages, which was prevented in NGAL-KO mice (&#x2009;<&#x2009;0.01). This effect was in accordance with the prevention of kidney increases in TNF-&#x3b1; and iNOS mRNA levels after AO (&#x2009;<&#x2009;0.05). Finally, AO significantly increased collagen deposition in the kidneys of WT mice (&#x2009;<&#x2009;0.05) and the expression of collagen-1, which was prevented in NGAL-KO mice (&#x2009;<&#x2009;0.01). Our results suggest that NGAL is required for albumin-induced kidney inflammation and fibrosis in mice in the AO model, which appears to be independent of changes in kidney function.