MO630: Association Between Inflammatory Markers and Progression of Diabetic Kidney Disease
Authors: Vasilkova Volha , Mokhort Tatiana , Pchelin Ivan 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Diabetes mellitus is the major cause of end-stage renal disease. Patients with diabetic kidney disease (DKD) have a higher risk of mortality, mostly from cardiovascular complications. Previous studies have shown that inflammatory cytokines are involved in the pathogenesis of microvascular diabetic complications, including DKD. Standard biomarkers including serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria are relatively insensitive to small changes in renal function. Thus, availability of novel biomarkers is necessary to detect kidney injury and predict clinically significant outcomes in diabetic patients. The aim of our study was to find relation between serum inflammatory and growths markers and CKD in patients with DT2.

METHOD
A total of 155 patients with DT2, aged 34–84 years [60 (60; 72)], were examined. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein (hs-CRP), vascular endothelial growth factor A (VEGF-A) and fibroblast growth factor-23 (FGF-23) in baseline plasma samples. Renal function was assessed based on the levels of serum creatinine, cystatin C, eGFR, which was calculated according to the CKD-EPI formula, and albuminuria, which was assessed as albumin/creatinine ratio (A/C).

RESULTS
The levels of VEGF-A, FGF-23, TNF-α, hs-CRP and Il-6 were significantly higher in diabetic patients with CKD 5 in comparison with stages 1–4. There were positive significant association between VEGF-A, FGF-23, TNF-α, hs-CRP, IL-6 and markers of renal function (creatinine, A/K). Thus VEGF-A, TNF-α and hs-CRP showed a weak and moderate correlation with creatinine, while IL-6 and FGF-23 showed a strong correlation (r = 0.70, P &lt; 0.001, r = 0.71, P &lt; 0.001, respectively). In addition, IL-6 significantly correlated with cystatin C (r = 0.71, P &lt; 0.001). A strong negative correlation was also observed between IL-6 and eGFR (r=−0.73, P &lt; 0.001).
In both unadjusted and adjusted analyses, probability of decreased eGFR was associated strongly with FGF-23 (COR (95% CI 1.890); 1.362–2.622, P &lt; 0.001), IL-6 (1.527; 1.251–1.863, P &lt;.001), hs-CRP (1.405; 1.231–1.602, P &lt;.001).
When evaluating the dependence of the probability of decreased eGFR on the FGF-23 using the ROC analysis, the cut-off value of FGF-23 which corresponds to the highest Youden's J statistic was 0.9 pmol/L. The sensitivity and specificity of the method were 75.3% and 74.5%, respectively [AUC 0.832 ± 0.035 (95% CI 0.764–0.901), P &lt; 0.001].
The cut-off value of IL-6 was 3.1 mg/mL. The sensitivity and specificity of the method were 64.3% and 73.7%, respectively [AUC 0.750 ± 0.029 (95% CI 0.694–.807), P&lt;0.001].
The cut-off value of hs-CRP was 5.8 mg/L. The sensitivity and specificity of the method were 72.2% and 75.7%, respectively (AUC 0.749 ± 0.029 (95% CI 0.693–.806) P &lt; 0.001).

CONCLUSION
Involvement of mediators of inflammation and fibrogenesis in the processes of tubulointerstitial damage in patients with diabetes and CKD, confirmed by their negative correlation with GFR and positive with creatinine and albuminuria, indicates a high risk of a decrease in GFR in patients with diabetes with an increase in IL-6 ≥3.1 mg/mL, FGF-23 ≥0.9 pmol/L and hs-CRP ≥5.8 mg/mL along with traditional risk factors.