Pro-inflammatory cytokines are associated with podocyte damage and proximal tubular dysfunction in the early stage of diabetic kidney disease in type 2 diabetes mellitus patients

Abstract

Aims: To evaluate if there is a link between inflammation (expressed by inflammatory cytokines) and the early stage of diabetic kidney disease (DKD), as shown by markers of podocyte damage and proximal tubular (PT) dysfunction.

Methods: In this study were enrolled 117 type 2 DM patients (36-normoalbuminuria, 42-microalbuminuria, 39- macroalbuminuria), and 11 healthy subjects. Serum and urinary IL-1 alpha, IL-8, IL-18, urinary albumin:creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (podocalyxin, synaptopodin, nephrin) and of PT dysfunction (KIM-1, NAG) were assessed.

Results: In multivariable regression urinary Il-1 alpha correlated positively with podocalyxin and NAG (p < 0.0001, R²= 0.57); urinary IL-8 correlated directly with synaptopodin, NAG, nephrin, and KIM-1 (p < 0.0001, R² = 0.67); urinary IL-18 correlated directly with synaptopodin, NAG, and nephrin (p < 0.0001, R² = 0.59). Serum IL-1 alpha correlated positively with nephrin, synaptopodin, NAG (P < 0.0001, R² = 0.68); serum IL-8 correlated directly with synaptopodin and NAG (p < 0.0001, R² = 0.66); serum IL-18 correlated directly with NAG, KIM-1, and podocalyxin (p < 0.0001, R²=0.647).

Conclusions: Pro-inflammatory interleukins are associated with podocyte injury and PT dysfunction in early DKD. These could exert a key role in the pathogenesis of early DKD, before the development of albuminuria.

Keywords: Albuminuria; Diabetic kidney disease; Interleukins; Podocyte biomarkers; Proximal tubular dysfunction.