Fibroblast growth factor 23 (FGF23) which is produced in bone participates

Fibroblast growth factor 23 (FGF23) which is produced in bone participates LY-411575 in the maintenance of phosphate metabolism and can serve as a LY-411575 biomarker for cardiovascular adverse outcomes in patients with chronic kidney and end-stage renal disease. 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 usually a more reliable biomarker of AKI than FGF23 C-terminal ELISA (a mixed LY-411575 readout of C-terminal fragment Rabbit Polyclonal to C1QB. 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 usually 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. =0.97) suggesting that in this animal model the augmentation of circulating FGF23 was first driven by the C-terminal fragment at early phase and possibly later by intact FGF23 following the kidney insult (Table 1) [34]. The exact time profile of FGF23 C-terminal fragment vs. intact FGF23 in AKI still needs to be defined. To identify novel risk factors for AKI hospitalizations which frequently occur in the elderly Brown and colleagues screened single measurements of plasma FGF23 C-terminal ELISA in 3241 community-dwelling elderly individuals without significant pre-existing kidney disease in the cohort of the Cardiovascular Health Study and analyzed the association of plasma FGF23 (sum of intact and C-terminal fragment) at study entry with the annual AKI event rate. After a median 10-year follow-up 119 (3.7%) subjects were hospitalized because of AKI. Adjudication of AKI hospitalizations was based on hospital discharge International Classification of Disease Ninth Revision Clinical Modification (ICD-9-CM) diagnosis codes for AKI as the primary diagnosis. The highest quartile of signal from FGF23 C-terminal ELISA (>100 RU/ml) was independently associated with a 2-fold higher risk of AKI hospitalization when the lowest quartile was used as the reference of comparison and after adjustment for kidney disease parameters such as estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (Table 1). A similar risk of AKI hospitalization was found in the lowest quartile of eGFR inferred from LY-411575 serum cystatin C. However no linear relationship (eg the higher the levels the higher the risk) between FGF23 levels and AKI hospitalization risk was found when FGF23 C-terminal ELISA-based levels were 54-100 RU/ml particularly after adjustment for cardiovascular and kidney disease parameters as confounders. Only FGF23 C-terminal ELISA signal >100 RU/ml was found to be consistently and independently associated with a higher risk of AKI hospitalization in this community-dwelling elderly population [35]. Again the biologic significance of this obtaining is usually unclear. It is conceivable that FGF23 may be a covariate of factors that were not accounted for in the adjustment of confounders. High circulating FGF23 and adverse outcomes in acute kidney injury One case-control study of 30 AKI patients and 30 non-AKI controls performed FGF23 C-terminal ELISA at enrollment (within 24 hours of AKI onset) and 5 days later [31]. This study showed that FGF23 C-terminal ELISA-based levels at enrollment were significantly higher in AKI patients (1471 RU/ml) than in controls (263 RU/ml) (Table 1). The levels were reduced to 459 RU/ml at day 5 in patients with AKI characterizing the transient nature of the elevation. Interestingly the plasma FGF23 C-terminal ELISA signal was higher in both AKI cases and controls if the subjects LY-411575 were in the medical ICU (1893 and 322 RU/ml respectively) when compared to those in the hospital wards (710 and 205 RU/ml respectively). The obtaining of higher FGF23 in non-AKI subjects in the ICU than those in the general wards indicates that this elevation of FGF23 in critically ill nonsurgical patients is usually impartial of AKI episode which was comparable to that in non-AKI subjects post cardiac surgery [34]. This observation highlights the potential contribution of.