Assessment and prediction of diabetic kidney disease in patients with type 2 diabetes mellitus by using an advanced biomarkers

Background

Diabetic kidney disease (DKD), is the major microvascular complication of diabetes, affecting on 40% of type 2 diabetic patients, is the leading cause of end-stage renal failure. Microalbuminuria has limited diagnostic role in early-stage diabetic kidney disease, because renal damage usually occurs before proteinuria. Therefore, more sensitive and specific biomarkers are needed for early detection of DKD.

Aims

The aim of this study was to determine the levels of monocyte chemoattractant protein-1 (MCP-1) and Wnt inducible signaling pathway protein 1 (WISP1) in type 2 diabetic patients and using them as a better diagnostic biomarker in the early phase of DKD.

Materials and methods

A case–control study involved 180 participants aged from 40 to greater than 60 years, 60 individuals are healthy, 120 person with type 2 diabetes mellitus (T2DM), they were divided in three groups by using urinary albumin/creatinine ratio (UACR): Group 1: 40 patients with normoalbuminuria (ACR < 30 mg/g creatinine). Group 2: 40 patients with microalbuminuria (ACR 30–300 mg/g creatinine). Group 3: 40 patients with proteinuria (ACR > 300 mg/g creatinine). Both serum MCP-1 and WISP1 levels were measured by an enzyme-linked immunosorbent assay (ELISA) the sandwich method. The patients were also assessed for duration of disease, fasting blood glucose, glycated hemoglobin, serum creatinine and blood urea. Urine albumin/creatinine ratio was determined by measurements of albumin and creatinine in morning urine sample.

Results

There was a significant elevation for all parameters in diabetic patients compared to control when estimated glomerular filtration rate (eGFR) decreased. The prevalence of DKD was found higher in male than in female and the majority of patients were older than ≥60 years. A significant difference with regards to age, body mass index (BMI) and duration of DM was found p ≤ 0.001. The mean of MCP-1 and WISP1 levels were higher in T2DM patients as compared with control group. MCP-1 was (152.85 ± 129.78), (137.24 ± 93.3), (70.93 ± 24.34) and (20.43 ± 6.04 pg/mL) in proteinuria, microalbuminuria, normoalbuminuria and control groups respectively. WISP1 was (125.83 ± 41.4), (94.58 ± 26.9), (59.44 ± 21.28) and (24.64 ± 7.6 pg/mL) in proteinuria, microalbuminuria, normoalbuminuria and control groups respectively. MCP-1 had a strong association with blood urea, serum creatinine and an inverse association with eGFR. There was significant positive correlation between the WISP1 and urea. In contrast there was positive correlations with creatinine only in microalbuminuria and proteinuria groups, while no correlation was found with eGFR. For early diagnosis and detection of DKD revealed that the cut-off value of serum MCP-1 was >34.9 pg/mL, with 97.5% sensitivity and 100% specificity in normoalbuminuria; >41.8 pg/mL, with 97% sensitivity and 100% specificity in microalbuminuria; and >49.25 pg/mL with both 100% sensitivity and specificity in proteinuria. Whereas, WISP1 was >25 pg/mL with 80% sensitivity and 51% specificity in normoalbuminuria; >34.3 pg/mL with 50% sensitivity and 96% specificity in microalbuminuria; and >60 pg/mL with 97% sensitivity and 83% specificity in proteinuria.

Conclusion

These findings proposed that MCP-1 may considered as potential predictor and prognostic biomarkers for the DKD while WISP1 may be considered as potential prognostic biomarkers for the DKD.