The Role of Netrin-1 and Interleukin-6 in Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus

Background: Netrin-1 is a laminin like protein highly induced after acute and chronic kidney injury, represent tubular damage and excreted in urine of both animals and humans. Netrin-1 is a potential biomarker predicting the development of diabetic kidney disease. Interleukin-6 (IL-6) is an inflammatory cytokine that has a role in the transformation from acute to chronic inflammation. The aim of this work was to evaluate the role of Netrin-1 and IL-6 in the development of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM).

Methods: Our study included 75 patients with T2DM and 25 healthy control group. The study duration started from October 2019 to January 2021. Participants were subdivided into four equal groups: group I: 25 healthy subjects as control group, group II: 25 diabetic patients with albumin/creatinine ratio < 30 mg/g, group III: 25 diabetic patients with albumin/creatinine ratio 30-300 mg/g, group IV: 25 diabetic patients with albumin/creatinine ratio > 300 mg/g. All subjects underwent complete clinical examination, laboratory investigations and measurement of serum Netrin-1 and IL-6 by ELISA.

Results: Nertin-1 was significantly higher in group III and group IV than group II and control group (P<0.001*). Netrin-1 was positively correlated with IL-6, fasting BG, 2HPP, HbA1C, B. urea, S. creatinine and urinary ACR, but it was negatively correlated with eGFR, Hb and S. albumin. IL-6 was significantly higher in group IV than group III, group II and control group (p<0.001*). There was a positive correlation between IL-6 and 2HPP, HbA1C, B. urea, S. creatinine and urinary ACR, but there was a negative correlation between IL-6 and eGFR, Hb and S. albumin. Netrin-1 was more sensitive 96.5% and more specific 99.8% than IL-6 sensitivity 83.3% and specificity 85.0%.

Conclusions: Netrin-1 and IL-6 were significantly higher in diabetic nephropathy patients with macroalbuminuria than other groups. Netrin-1 was more sensitive and specific than IL-6 in predicting DN and its progression.