Abstract
BACKGROUND: Endothelial dysfunction is the primary step for the development of CKD-related cardiovascular disease. Early prediction and management can influence patient survival. Serum testing of FGF 23 hormone and urinary phosphate excretion were studied as predictors of all-cause cardiovascular morbidity in CKD patients; however, their relation to endothelial dysfunction is controversial. A combination of both in one index is hypothesized to increase their sensitivity in detecting endothelial dysfunction, especially in the early stages of CKD before the dominance of hyperphosphatemia, the original risk. METHODS: A cross-sectional comparative analysis between thirty CKD stage 3 patients and sixty stage 4-5 CKD patients was conducted. All patients were tested for markers of mineral bone disorders including serum FGF 23 and 24-h urinary phosphate excretion. A combination of both in one index (nephron index) is calculated and hypothesized to correlate with nephron number. Endothelial dysfunction was assessed by measuring the post-occlusion brachial flow-mediated dilatation (FMD). RESULTS: In univariate and multivariate regression analyses, the nephron index was the only predictor of endothelial dysfunction in individuals with stage 3 CKD (r = 0.74, P 0.01). This was not applied to stage 4-5 CKD patients where serum phosphorus (r = - 0.53, P 0.001), intact PTH (r = - 0.53, P 0.001), uric acid (r = - 0.5, P 0.001), and measured GFR (r = 0.59, P 0.001) were the highest correlates to FMD; the Nephron index had the weakest correlation (r = 0.28, P = 0.02) and is not predictive of endothelial dysfunction. CONCLUSION: Nephron index calculation showed better correlation with endothelial dysfunction than using any of its determinants alone in early stages of CKD when FGF 23 levels are just beginning to rise. In advanced CKD patients, hyperphosphatemia, hyperparathyroidism, hyperuricemia, and measured GFR are more reliable than nephron index.