Diagnostic Performance of Biomarkers Urinary KIM-1 and YKL-40 for Early Diabetic Nephropathy, in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Abstract

There is a lack of prediction markers for early diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). The aim of this systematic review and meta-analysis was to evaluate the performance of two promising biomarkers, urinary kidney injury molecule 1 (uKIM-1) and Chitinase-3-like protein 1 (YKL-40) in the diagnosis of early diabetic nephropathy in type 2 diabetic patients. A comprehensive search was performed on PubMed by two reviewers until May 2020. For each study, a 2 × 2 contingency table was formulated. Sensitivity, specificity, and other estimates of accuracy were calculated using the bivariate random effects model. The hierarchical summary receiver operating characteristic curve hsROC) was used to pool data and evaluate the area under curve (AUC). The sources of heterogeneity were explored by sensitivity analysis. Publication bias was assessed using Deek’s test. The meta-analysis enrolled 14 studies involving 598 healthy individuals, 765 T2DM patients with normoalbuminuria, 549 T2DM patients with microalbuminuria, and 551 T2DM patients with macroalbuminuria, in total for both biomarkers. The AUC of uKIM-1 and YKL-40 for T2DM patients with normoalbuminuria, was 0.85 (95%CI; 0.82–0.88) and 0.91 (95%CI; 0.88–0.93), respectively. The results of this meta-analysis suggest that both uKIM-1 and YKL-40 can be considered as valuable biomarkers for the early detection of DN in T2DM patients with the latter showing slightly better performance than the former.

Novel Cardiovascular Risk Factors in Patients with Diabetic Kidney Disease

“…Kidney injury molecule-1 (KIM-1) is a type 1 epithelial transmembrane glycoprotein, and its expression is upregulated in the proximal tubules of the kidney following an ischemic insult [ 20 ]. Patients with diabetic nephropathy have higher KIM-1 levels than controls [ 5 , 21 , 22 , 23 ]. Moreover, KIM-1 levels correlate with GFR and urinary albumin excretion [ 5 , 8 , 24 , 25 , 26 ].…”

Myokines: Novel therapeutic targets for diabetic nephropathy

“…Serum YKL-40 levels were significantly increased in the group with persistent proteinuria compared with those in the other groups and correlated with the urinary albumin/creatinine ratio ( 64 ). Similarly, the level of YKL-40 was found to be increased in the early stage of DN and was correlated DN progression ( 65 , 66 ). These findings suggest that YKL-40 may be used as a diagnostic indicator for early-stage of DN.…”

Potential biomarkers of chronic kidney disease progression among kidney-derived proteins; a review

“…A study revealed that patients who underwent peritoneal dialysis and hemodialysis had elevated levels of YKL-40 when compared to healthy individuals. YKL-40 is a predictor of diabetic nephropathy with a sensitivity of 83% and specificity of 85% (24). Elevated levels of YKL-40 measured by ELISA in patients with different stages of CKD.…”