Aim: To estimate the differences in the panel of circulating cytokines mediating low-grade inflammation and fibrosis in patients with type 2 diabetes (T2D) and chronic kidney disease.Methods: We examined 130 patients with T2D duration ≥10 years. Among them, 65 individuals had reduced estimated glomerular filtration rate (eGFR; 15-59 ml/min/1.73 m2) and 64 patients had increased albuminuria. Thirty healthy subjects were acted as control. Serum IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17A, bFGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF were assessed by multiplex analysis. Urinary nephrin and podocin, as podocyte injury markers, and WFDC-2, a marker of tubulointerstitial fibrosis, were assessed by ELISA.
Results: Patients with T2D and reduced eGFR had increased levels of IL-1ra, IL-8, IL-13 and decreased IL-7, IL-9 and IL-15 concentrations when compared to those with preserved renal function and control (all p<0.05). Excretion of WFDC-2, but not podocyte markers, was increased in these patients (p≤0.02). The elevation of albuminuria was associated with enhanced excretion of nephrin and podocin (p<0.0001), but no differences were found in the levels of all measured cytokines between patients with normal and elevated albuminuria. The levels of IL-2, IL-4, IL-5, IL-17A, bFGF, G-CSF, IP-10 and MIP-1α correlated negatively with eGFR. No correlations were found between measured cytokines and glomerular markers. There was positive correlation between WFDC-2 and MIP-1α. The levels of IL-10 and IL-15, two anti-inflammatory cytokines, correlated negatively with WFDC-2.
Conclusion: The obtained results demonstrate that decreased eGFR and increased urinary excretion of WFDC-2, a marker of tubulointerstitial fibrosis, are associated with a predominance of pro-inflammatory and fibrogenic molecules in the panel of circulating cytokines in T2D subjects.
A.I. Korbut: None. O. Fazullina: None. V. Klimontov: None.