Urinary RANTES and MCP-1 as noninvasive biomarkers for differential diagnosis and prediction of treatment response in acute interstitial nephritis.

Abstract

Background: Although kidney biopsy is definitive for the diagnosis of acute interstitial nephritis (AIN) and acute tubular necrosis (ATN), its invasiveness limits its use. We aimed to identify urine biomarkers for differentiating AIN and ATN and to predict the response of patients with AIN to steroid treatment.

Methods: In this prospective cohort study, biopsy-proven ATN (n = 34) and AIN (n = 55) were included. Urinary cytokine/chemokine [interleukin-9, monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-α, tumor growth factor-β and vascular endothelial growth factor] levels and the proportion of immune cells [expressing cluster of differentiation (CD)45, CD3, CD20] and proliferating tubular cells (expressing Ki-67) were analyzed by immunohistochemistry. Cytokine/chemokine levels and intrarenal immunohistochemistry data according to the response to steroid treatment in the AIN patients were also analyzed.

Results: The urinary RANTES/creatinine ratio and the percentages of intrarenal CD45-, CD3-, CD20- and Ki-67-positive cells were significantly higher in the AIN group than in the ATN group (P < .05 for all). Among steroid-administered patients with AIN, renal function improved significantly in the steroid responder group. These patients had higher urinary MCP-1/creatinine and intrarenal CD45 and Ki-67 levels than those in the non-responder group.

Conclusions: The potential of the urinary RANTES/creatinine ratio as a noninvasive biomarker for differentiating AIN from ATN is highlighted. Urinary MCP-1/creatinine levels and the proportion of total intrarenal leukocytes and proliferating tubular cells may serve as indicators for predicting the response of patients with AIN to steroid treatment.