YKL-40: A biomarker for early nephropathy in type 2 diabetic patients and its association with inflammatory cytokines

Abstract

Diabetic Nephropathy (DN) is an important cause of morbidity and death amongst diabetes. Persistent micro and macroalbuminuria are well known predictors of DN leading to progressive end-stage renal disease. However, albuminuria has several limitations. Increasing evidences show that YKL-40 is highly expressed in variety of inflammatory diseases and also recognized as a non-invasive prognostic biomarker for inflammation. In the present study, we measured plasma YKL-40 levels in different stages of albuminuria and assessed its diagnostic accuracy as a biomarker for DN and correlated with different families of circulatory cytokines. A total of 306 subjects were recruited and divided into three groups [Group-I, control (n = 83), Group-II, Normoalbuminuria (n = 81), Group-III, DN (n = 142)]. Group-III is further subdivided into: Group-IIIa, microalbuminuria (n = 73), Group-IIIb, macroalbuminuria (n = 69). The median levels of YKL-40 (p = 0.001) showed a marked stepwise increase from normo to macroalbuminuria and positively correlated with eGFR. The AUC_ROC for YKL-40 was found to be high [0.95; (95% CI: 0.88-1.0)], when compared to other acute phase markers. Plasma YKL-40 showed a positive correlation with LIGHT/TNFSF14, sIL-6Ra, gp130/sIL-6Rβ, IFN-β, IL-8, TNFSF14, sCD-30 and eGFR meanwhile a negative correlation with TWEAK/TNFSF12, IL-7 like cytokine and IFN-λ2. Plasma YKL-40 could be a potential biomarker for early diagnosis of incipient DN among South Indian population.

Keywords: Cytokines; Diabetic Nephropathy; Inflammation; Type-2-diabetes; YKL-40.