The Relationship of Certain Physiological Parameters and VEGF with chronic kidney disease

Abstract

Chronic kidney disease (CKD) is a major health burden affecting over 10% of the global population. As kidney function deteriorates across progressive CKD stages, systemic inflammation and cytokine activity are upregulated which further drive disease advancement. Vascular endothelial growth factor (VEGF) also becomes increasingly dysregulated with implications for vascular pathology. However, step-wise changes in these pathways correlating with declining renal filtration have not been clearly elucidated : Objective: This study aimed to evaluate the utility of estimated glomerular filtration rate (eGFR) using the MDRD equation for disease staging, and to explore potential non-invasive biomarkers, including inflammatory markers and vascular endothelial growth factor (VEGF) expression, for early prediction of renal dysfunction; Methods: 50 CKD patients categorized into stages 1-4 (n=10 each) and 10 healthy controls were recruited. Serum creatinine was measured enzymatically and eGFR calculated. Plasma TNF-alpha and CRP concentrations were determined by ELISA. Relative VEGF mRNA levels were quantified by RT-qPCR and normalized to GAPDH; Results: Advancing CKD stage showed step-wise increases in serum creatinine (p<0.001) and reductions in mean eGFR (p<0.001). TNF-alpha and CRP also demonstrated significant stage-dependent elevations beginning from early stage 2 disease relative to controls (p<0.01). VEGF expression escalated progressively from ~3 fold in stage 2 to ~129 fold in stage 4 CKD compared to normal individuals (p<0.001); Conclusions: Deteriorating renal function is associated with substantive aggravations in systemic inflammation and VEGF expression. Tracking these biomarkers could enable early detection of underlying pathology prior to onset of severe kidney impairment.