Serum CXCL16 as a novel marker of renal injury in type 2 diabetes mellitus

Abstract

Background: Soluble C-X-C chemokine ligand 16 (CXCL16), a scavenger receptor for oxidized low density lipoprotein, has been shown to promote atherogenic effects in vivo and to predict long-term mortality in acute coronary syndrome. The aim of this study was to explore the association of circulating CXCL16 levels with diabetic subjects with and without renal disease.

Methodology/principal findings: One hundred twenty Chinese subjects, which included patients with type 2 diabetes mellitus (T2DM), diabetic nephropathy (DN), and CKD, as well as healthy controls, were enrolled in this study. Serum CXCL16 levels were examined by immunoassay and other clinical biochemical parameters were tested based on standard methods. Our results indicated that, HDL and LDL cholesterol levels are significantly different in DN but not in T2D patients in comparison with healthy subjects. On the other hand, Serum CXCL16 levels were significantly increased in DN subjects compared with age and gender matched healthy and T2DM subjects (p<0.05 respectively). However, no significant changes in serum CXCL16 levels were found between T2DM and healthy subjects. Furthermore, serum CXCL16 concentration negatively correlated with estimated glomerular filtrate rate, creatinine clearance rate and blood albumin, and positively with 24 h proteinuria, blood urea nitrogen (BUN), creatinine, and uric acid after adjusting for age, gender and BMI in subjects with DN. Multiple stepwise regression analyses indicated that serum CXCL16 levels were independently associated with serum 24 h proteinuria, and BUN (p<0.05 respectively).

Conclusion: Serum CXCL16 may be an indicator of renal injury in subjects with T2DM. Understanding the exact mechanism of elevated CXCL16 in subjects with DN requires further study.

Figure 1. Serum concentration of total cholesterol(A), HDL (B), LDL (C), and triglycerides (D) among T2DM, DN, CKD, and healthy subjects.

*, p<0.05.

Figure 2. Serum concentration of CXCL16 (A), creatinine (B), BUN (C), and uric acid (D) among T2DM, DN, CKD, and healthy subjects.

*, p<0.05; **, p<0.01; ***, p<0.001.

Figure 3. Correlation of serum CXCL16 levels with CCR (A), eGFR (B), creatinine (C), BUN (D), 24 h proteinuria (E), and blood albumin (F) in subjects with DN.