Association of Indoxyl Sulfate With Fibroblast Growth Factor 23 in Patients With Advanced Chronic Kidney Disease

Abstract

BackgroundProtein-bound uremic toxins–indoxyl sulfate (IS) and p-cresyl sulfate (PCS)–can not only predict clinical outcomes but also may relate to bone-mineral disorders in patients with chronic kidney disease (CKD). However, the relationship between protein-bound uremic toxins and fibroblast growth factor 23 (FGF23) has not been studied before. The objective of this study was to explore the association of IS and PCS with FGF23 in a CKD-based cohort. MethodsThis is a cross-sectional study that enrolled 80 stable CKD stage 3 to 5 patients who met the inclusion criteria in a single medical center. Serum levels of IS, PCS and FGF23 were measured concurrently. General biochemistry and patient background were also investigated. ResultsSerum FGF23 and IS concentrations were elevated commensurately with deteriorating renal function. Pearson's analysis showed that FGF23 levels were significantly associated with blood urea nitrogen (r=0.381, P<0.05), creatinine (r=0.632, P<0.01), estimated glomerular filtration rate (r=–0.447, P<0.05), phosphate (r=0.543, P<0.01), intact parathyroid hormone (r=0.543, P<0.01), IS (r=0.432, P<0.01) and PCS (r=0.318, P<0.05). After adjusting other confounding factors by stepwise multiple linear regression analysis, only creatinine (β=0.82, P<0.01), phosphate (β=0.28, P=0.02) and IS (β=0.39, P=0.04) retained statistically significant associations with FGF23. Moreover, serum levels of IS were higher in patients with high FGF23 concentration (>90pg/mL, median value) than those with lower FGF23 (P<0.01). ConclusionsResults indicated that only IS but not PCS correlated independently with FGF23 in worsening CKD. IS may be an independent factor involved in regulation of bone-mineral metabolism.