Role of kidney injury molecule 1 and nephrin as biomarkers for diagnosis of nephropathy in type 2 diabetes mellitus

Abstract

Background Diabetic nephropathy (DN) is a significant complication of diabetes caused by alterations within the structure and function of the kidneys. This increases the need for novel biomarkers that might predict nephropathy. Kidney injury molecule 1 (KIM-1) is a type 1 membrane protein present on the apical membrane of proximal tubules. It has a possible role in predicting long-term renal outcome. Thus, it serves as a selected and sensitive biomarker for proximal tubule damage. Nephrin is a transmembrane protein in the structure of the slit diaphragm. The study aimed to assess the levels of urinary KIM-1 and nephrin to detect early changes of renal functions in patients with type 2 diabetes mellitus (T2DM) and to assist in the prevention. Patients and methods This is a prospective study comprising 60 patients with T2DM. Patients were divided into three groups by their urinary albumin/creatinine ratio. Peripheral hemogram, liver and renal functions, lipogram, glycosylated hemoglobin (HbA1C), urine albumin/creatinine ratio, urinary KIM-1, and nephrin were done. Patients with type 1 DM, fever, infection, gestational diabetes, as well as evidence of systemic disease were excluded. Moreover, 28 volunteers were included. Results In this study, urinary nephrin and KIM-1 were significantly higher in those with macroalbuminuria, microalbuminuria, and those with normoalbuminuria compared with the control group. Both nephrin and KIM-1 had a significant positive correlation with creatinine in patients with macroalbuminuria and patients with microalbuminuria. Multivariate logistic regression analysis showed that the odds ratio for the presence of DN in the highest KIM-1 was 3.01 (95% confidence interval = 2.11–5.60; P < 0.001), nephrin was 2.9 (95% confidence interval = 1.10–4.65; P < 0.001), and HbA1C was 2.23 (95% confidence interval = 1.94–4.11; P < 0.001). By using receiver operating characteristic, it was noticed that the level of nephrin with cutoff value of more than 10 μg/ml was able to detect the diagnosis and prognosis of DN in our patients with sensitivity of 95%, specificity of 94%, and positive predictive value of 98.2%. Conclusion Urinary KIM-1 and nephrin levels appear to increase in kidney injury secondary to DN in the early period regardless of albuminuria, as urinary KIM-1 and nephrin were increased, even though there was normal urinary albumin excretion in the normoalbuminuric group. The study revealed that KIM-1, nephrin, and HBA1C were independent predictors of DN.