Elevated urinary IL-36α and IL-18 levels are associated with diabetic nephropathy in patients with type 2 diabetes mellitus

BACKGROUND: Inflammatory cytokines have been reported to be pathogenic factors for the development and progression of diabetic nephropathy (DN). Interleukin (IL)-36 alpha is a newly discovered member of the IL-1 cytokine family that has been implicated in animal models of renal impairment. However, little is known about the role of IL-36 alpha in DN in humans. The purpose of the present study was to assess the levels of IL-36 alpha and IL-18 in type 2 diabetic patients (T2DM) patients with and without DN. METHODS: Subjects were divided into 3 groups: Control (N.=20), T2DM without DN (N.=30), and T2DM with DN (N.=30). Urinary IL-36 alpha and IL-18 levels were assessed using ELISA. Correlation analysis was performed to determine the association of the IL levels with clinical markers of T2DM and DN. RESULTS: IL-36 alpha and IL-18 levels were significantly elevated in T2DM patients with DN, when compared to T2DM patients without DN (P<0.0001, P=0.0025, respectively) and controls (P<0.0001, for both). IL-36 alpha levels showed a positive correlation with urinary albumin excretion (r=0.754, P<0.0001), HbA1c (r=0.433, P=0.0168), fasting plasma glucose (r=0.433, P=0.0168) and negative correlation with glomerular filtration rate (r=-0.852 P<0.0001). CONCLUSIONS: The results highlighted the association of IL-36 alpha with DN. However, further extensive studies are suggested for evaluating the association.

Automated summary

Inflammatory cytokines such as IL-36 alpha have been implicated in the pathogenesis of diabetic nephropathy, with levels significantly elevated in T2DM patients with DN. IL-36 alpha levels were found to correlate positively with urinary albumin excretion, HbA1c, and fasting plasma glucose, and negatively with glomerular filtration rate. Further extensive studies are recommended to evaluate this association.