Urinary monocyte chemotactic protein 1 as a predictive marker of steroid responsiveness in children with idiopathic nephrotic syndrome

Abstract

Objective: We previously reported that macrophages contribute to the pathogenesis of refractory nephrotic syndrome (NS). To elucidate the mechanism behind macrophage accumulation and to identify a predictive biomarker of steroid responsiveness, we compared differences in cytokine and chemokine levels in serum and urine between steroid-sensitive (SSNS) and steroid-resistant (SRNS) children with NS. Methods: Eighteen children with NS (7.1±4.3 years; male-to-female ratio, 12:6) were divided into an SSNS group (n=10) and an SRNS group (n=8) according to their clinical course. Serum and urinary samples were collected at the time of onset and remission. Samples from age-matched healthy children were used as controls (n=15). Cytokines and chemokines were measured using a cytometric bead array kit. Results: Clinical findings and laboratory data at sampling were comparable between the SRNS and SSNS groups. Serum cytokines and chemokines did not significantly differ at the time of onset between remission and control groups. In contrast, at onset, several urinary chemokines were significantly elevated in children with NS (IP-10, MCP-1, MIG, RANTES; all p<0.01). Urinary MCP-1 levels were significantly elevated in the SRNS group compared with the SSNS group (p<0.01). Conclusions: Chemokines might be associated with the pathogenesis of NS. Increased urinary excretion of MCP-1 in children with SRNS is a potential predictive biomarker of steroid responsiveness in idiopathic NS. Further histological studies, including macrophage accumulation, are required to determine the mechanisms of steroid resistance in refractory NS.

Keywords

• biomarkers
• macrophages
• monocyte chemotactic protein-1
• steroid-resistant nephrotic syndrome
• urinary chemokines