Circulating 18-Glycosyl Hydrolase Protein Chitiotriosidase-1 is Associated with Renal Dysfunction and Systemic Inflammation in Diabetic Kidney Disease

Int J Appl Basic Med Res. 2023 Jul-Sep;13(3):159-167. doi: 10.4103/ijabmr.ijabmr_42_23. Epub 2023 Sep 25.

Abstract

Introduction: Chitotriosidase-1 (CHIT-1) is a marker of macrophage activation and recently attributed to type 2 diabetes mellitus (T2DM). However, its role in the development and progression of diabetic kidney disease (DKD) has been sparsely discussed in the recent literature.

Materials and methods: In this cross-sectional exploratory study, 81 participants with T2DM were classified into two groups based on the presence of DKD. Their anthropometric, biochemical, and pathological profiles were estimated. Circulatory CHIT-1 concentration was determined using the enzyme-linked immuno-sorbent assay (ELISA) in plasma.

Results: CHIT-1 was significantly elevated in diabetic nephropathy, independent of age and gender. It is associated with severity of kidney disease, as assessed using urinary protein-creatinine ratio (uPCR) in a multiple linear regression model, independent of age, gender, diabetes duration, and insulin resistance. CHIT-1 positively predicted the likelihood of DKD in the study population (area under the curve = 0.724, P < 0.05). The duration of diabetes correlated positively with uPCR and negatively with estimated glomerular-filtration rate. Neutrophil-Lymphocyte ratio was elevated in participants with DKD. This well-established marker of systemic inflammation exhibited significant positive association with CHIT-1.

Conclusion: Plasma CHIT-1 protein is elevated in DKD and associated with disease progression. It is capable of reflecting disease severity and is closely related to systemic inflammation possibly caused by pro-inflammatory circulatory immune cells.

Keywords: Chronic low-grade inflammation; diabetic kidney disease; neutrophil-lymphocyte ratio; systemic inflammation; type 2 diabetes mellitus.