Preoperative plasma FGF23 levels predict acute kidney injury in children: results of a pilot study

Ali, Farah; Hassinger, Amanda; Price, Heather E.; Langman, Craig B.

doi:10.1007/s00467-012-2395-2

Cited by 29 publications

(37 citation statements)

References 18 publications

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“…Ali et al followed a cohort of 19 pediatric patients without CKD who were scheduled to undergo cardiac surgery. [35] Of those, 5 children developed AKI post-operatively. Pre-operative FGF23 levels were higher in the patients who went on to develop AKI (median 323 vs 69 RU/mL) and peak FGF23 levels measured within 4 days post-operatively were also higher in the AKI group (median 1010 vs 196 RU/mL).…”

Section: Alterations In Fgf23 In Akimentioning

confidence: 99%

“…Interestingly, preoperative FGF23 levels also correlated with increased fluid gain and longer ventilation time post-operatively. [35] While the authors speculate that the elevated levels pre-operatively may indicate a derangement in renal function undetectable by conventional measures such as creatinine or cystatin C, an alternative explanation would be that the pre-operative levels reflect a poorer cardiac status in those 5 patients (who as a group had a nearly double cross-clamp time during the surgery compared with controls). Elevated FGF23 levels have been reported in pediatric patients with heart failure but without CKD and correlate with severity of heart failure and left ventricular dilation.…”

Section: Alterations In Fgf23 In Akimentioning

confidence: 99%

“…[7] In the above admittedly small studies, elevated FGF23 levels correlated with mortality, the composite of death/ need for RRT or with length of ICU stay and length of ventilation. [33-35] Analysis of larger cohorts of patients with AKI is necessary to see if these findings can be replicated. Even if they are, many unanswered questions will still remain regarding causality and potential mechanisms to explain these observations.…”

Section: Implications For Elevated Fgf23 In Akimentioning

confidence: 99%

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Fibroblast growth factor 23 in acute kidney injury

Christov

2014

Current Opinion in Nephrology and Hypertension

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Purpose of review to review emerging literature on changes in fibroblast growth factor 23 (FGF23) levels in the setting of acute kidney injury. Recent findings studies suggest that FGF23 levels are elevated in patients with acute kidney injury, and correlate with increased risk of death or need for dialysis (in adults) or prolonged ventilation time and higher fluid gain (in children). Animal work shows that the etiology behind this FGF23 increase is multi-factorial and includes increased production in bone and decreased clearance, but not vitamin D or PTH-activated pathways. Interestingly, FGF23 levels were found to be mildly elevated even in hospitalized patients without kidney injury, although this observation may be limited to only c-terminal FGF23 fragments. The prognostic implications of an elevated FGF23 value in patients with acute kidney injury need to be confirmed in larger cohorts and evaluated for long-term outcomes such as development of new CKD or CKD progression, as well as cardiovascular disease, similar to studies of FGF23 in the prevalent CKD population. Summary FGF23 levels are elevated in patients with AKI and are associated with morbidity and mortality is small human studies. Mechanistic work in animals suggests that the elevation is independent of PTH or vitamin D-signaling pathways. Much work remains to understand the physiology behind FGF23 elevation and the long-term effects of FGF23 in AKI.

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Section: Alterations In Fgf23 In Akimentioning

confidence: 99%

Section: Alterations In Fgf23 In Akimentioning

confidence: 99%

Section: Implications For Elevated Fgf23 In Akimentioning

confidence: 99%

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Fibroblast growth factor 23 in acute kidney injury

Christov

2014

Current Opinion in Nephrology and Hypertension

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“…In a murine model of AKI, circulating FGF23 levels increased as early as one hour after AKI induction, and did so independently of phosphate, calcitriol, and PTH (7). Studies in humans with AKI have demonstrated that FGF23 concentrations, determined by the C-terminal assay, are increased in both adult (7–9) and pediatric (10) patients, and that these elevated levels are associated with poor clinical outcomes (8,9). However, it is unknown whether the high FGF23 levels in AKI reflect the intact, bioactive molecule or C-terminal fragments.…”

Section: Introductionmentioning

confidence: 99%

Effects of acute kidney injury and chronic hypoxemia on fibroblast growth factor 23 levels in pediatric cardiac surgery patients

et al. 2015

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Background 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 measurements correlated inversely with FGF23 levels. Pre-operative cFGF23 and oxygen saturation both predicted post-operative AKI. Post-operatively, cFGF23 and iFGF23 increased by 2 hours post-reperfusion; iFGF23 then returned to baseline, but cFGF23 remained elevated through 24 hours post-reperfusion. Group status (AKI vs. non-AKI) modified the effect of time on changes in iFGF23 levels, but not cFGF23 levels. 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.

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“…Children with CKD were excluded and both pre- and post-operative plasma samples were analyzed [33]. Patients who developed AKI following cardiac surgery had elevated FGF23 C-terminal ELISA readings both pre- and post-operatively compared with children who did not develop AKI (Table 1).…”

Section: High Circulating Fgf23 Is Associated With Higher Risk Of Akimentioning

confidence: 99%

Fibroblast growth factor 23 and acute kidney injury

Neyra

Moe

2014

Pediatr Nephrol

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Fibroblast growth factor 23 (FGF23) which is produced in bone, participates in the maintenance of phosphate metabolism and can serve as a biomarker for cardiovascular adverse outcomes in patients with chronic kidney and end-stage renal disease. Circulating FGF23 rapidly increases after acute kidney injury (AKI), preceding other known markers such as neutrophil gelatinase-associated lipocalin and serum creatinine. The increase in FGF23 in AKI appears to be independent of parathyroid hormone, vitamin D signaling pathways and dietary phosphate. The potential mechanisms include: 1) increased production of FGF23 in the bone by yet-to-be-identified factors; 2) ectopic production of FGF23 by injured renal tubules; and 3) decreased renal clearance of circulating FGF23. Circulating FGF23 determined by intact FGF23 enzyme-linked immunosorbent assay (ELISA) is a more reliable biomarker of AKI than FGF23 C-terminal ELISA (a mixed readout of C-terminal fragment and intact FGF23). Given that FGF23 can be ectopically expressed in differentiated renal tubules and iron modulates FGF23 metabolism, an effect of iron on FGF23 expression in renal tubules is conceivable but remains to be confirmed. More clinical and experimental studies are required to validate the use of circulating FGF23 as a biomarker for the early identification of AKI and prediction of short- and long-term adverse outcomes post-AKI. More importantly, the biologic effect of increased FGF23 in AKI needs to be defined.

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Preoperative plasma FGF23 levels predict acute kidney injury in children: results of a pilot study

Cited by 29 publications

References 18 publications

Fibroblast growth factor 23 in acute kidney injury

Fibroblast growth factor 23 in acute kidney injury

Effects of acute kidney injury and chronic hypoxemia on fibroblast growth factor 23 levels in pediatric cardiac surgery patients

Fibroblast growth factor 23 and acute kidney injury

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