Effects of Acute Kidney Injury and Chronic Hypoxemia on Fibroblast Growth Factor 23 Levels in Pediatric Cardiac Surgery Patients

Background:Fibroblast growth factor 23 (FGF23) levels are elevated in cardiopulmonary bypass (CPB)-associated acute kidney injury (AKI); however, it is unknown how much of the circulating FGF23 is intact and bioactive. Hypoxia may induce FGF23 production, yet its impact in humans is unknown. Pediatric cardiac surgery patients have both a high incidence of CPB-associated AKI and a high prevalence of chronic hypoxemia. Methods:We assessed the effects of hypoxemia and CPB-associated AKI on C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels in 32 pediatric cardiac surgery patients with normal eGFR. Plasma cFGF23 and iFGF23 were measured pre-operatively and serially post-operatively. Results:Despite normal renal and ventricular function, pre-operative cFGF23 levels were high and elevated out of proportion to iFGF23 levels. Pre-operative oxygen saturation correlated inversely with FGF23. Pre-operative cFGF23 and oxygen saturation both predicted post-operative AKI. Post-operatively, cFGF23 and iFGF23 increased early post-reperfusion; although cFGF23 levels remained elevated, iFGF23 levels soon returned to baseline.Conclusions:Pre-operative cFGF23 may predict CPB-associated kidney dysfunction. Changes over time in cFGF23 and iFGF23 levels post-CPB differ. Chronic hypoxemia may affect FGF23 production in humans

Effects of Acute Kidney Injury and Chronic Hypoxemia on Fibroblast Growth Factor 23 Levels in Pediatric Cardiac Surgery Patients

Background:Fibroblast growth factor 23 (FGF23) levels are elevated in cardiopulmonary bypass (CPB)-associated acute kidney injury (AKI); however, it is unknown how much of the circulating FGF23 is intact and bioactive. Hypoxia may induce FGF23 production, yet its impact in humans is unknown. Pediatric cardiac surgery patients have both a high incidence of CPB-associated AKI and a high prevalence of chronic hypoxemia. Methods:We assessed the effects of hypoxemia and CPB-associated AKI on C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels in 32 pediatric cardiac surgery patients with normal eGFR. Plasma cFGF23 and iFGF23 were measured pre-operatively and serially post-operatively. Results:Despite normal renal and ventricular function, pre-operative cFGF23 levels were high and elevated out of proportion to iFGF23 levels. Pre-operative oxygen saturation correlated inversely with FGF23. Pre-operative cFGF23 and oxygen saturation both predicted post-operative AKI. Post-operatively, cFGF23 and iFGF23 increased early post-reperfusion; although cFGF23 levels remained elevated, iFGF23 levels soon returned to baseline.Conclusions:Pre-operative cFGF23 may predict CPB-associated kidney dysfunction. Changes over time in cFGF23 and iFGF23 levels post-CPB differ. Chronic hypoxemia may affect FGF23 production in humans

Non-renal-Related Mechanisms of FGF23 Pathophysiology

Purpose of reviewWe will review non-renal-related mechanisms of fibroblast growth factor 23 (FGF23) pathophysiology.Recent findingsFGF23 production and metabolism may be affected by many bone, mineral, and kidney factors. However, it has recently been demonstrated that other factors, such as iron status, erythropoietin, and inflammation, also affect FGF23 production and metabolism. As these non-mineral factors are especially relevant in the setting of chronic kidney disease (CKD), they may represent emerging determinants of CKD-associated elevated FGF23 levels. Moreover, FGF23 itself may promote anemia and inflammation, thus contributing to the multifactorial etiologies of these CKD-associated comorbidities. CKD-relevant, non-mineral-related, bidirectional relationships exist between FGF23 and anemia, and between FGF23 and inflammation. Iron deficiency, anemia, and inflammation affect FGF23 production and metabolism, and FGF23 itself may contribute to anemia and inflammation, highlighting complex interactions that may affect aspects of CKD pathogenesis and treatment