Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
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Nephrol. Dial. Transplant. · Sep 2013
ReviewFibroblast growth factor-23: what we know, what we don't know, and what we need to know.
Traditional risk factors of cardiovascular morbidity and mortality such as hypertension, hypercholesterolemia and obesity are paradoxically associated with better outcomes in dialysis patients, and the few trials of interventions targeting modifiable traditional risk factors have yielded disappointing results in this patient population. Non-traditional risk factors such as inflammation, anemia and abnormalities in bone and mineral metabolism have been proposed as potential explanations for the excess mortality seen in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), but without clear understanding of what the most important pathophysiologic mechanisms of these risk factors are, which ones might be ideal treatment targets and which therapeutic interventions may be effective and safe in targeting them. Among the novel risk factors, fibroblast growth factor-23 (FGF23) has recently emerged as one of the most powerful predictors of adverse outcomes in patients with CKD and ESRD. ⋯ While it is possible that 'off target' effects of FGF23 present in very high concentrations could induce LVH, this possibility is controversial, since α-klotho is not expressed in the myocardium. Another possibility is that FGF23's effect on the heart is mediated indirectly, via 'on target' activation of other humoral pathways. We will review the physiology and pathophysiology of FGF23, the outcomes associated with elevated FGF23 levels, and describe putative mechanisms of action responsible for its negative effects and potential therapeutic strategies to treat these.
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A standardized classification of acute kidney injury (AKI) has recently been proposed with the RIFLE (Risk, Injury, Failure, Loss of function, End-stage kidney disease) score. Such definition/classification has been applied both in adult and in paediatric patients. ⋯ Their so-called 'immature kidneys' require careful management and neonatal AKI is frequently complicated by unfavourable outcomes. A recent attempt to implement the RIFLE score with a neonatal modification might lead to improvement on the knowledge of AKI incidence and epidemiology.