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Introduction As periods of famine were an important aspect of the human evolutionary environment, the body's adaptive ability during periods of starvation was a key survival advantage. Fibroblast growth factor [...], In mice, FGF21 is rapidly induced by fasting, mediates critical aspects of the adaptive starvation response, and displays a number of positive metabolic properties when administered pharmacologically. In humans, however, fasting does not consistently increase FGF21, suggesting a possible evolutionary divergence in FGF21 function. Moreover, many key aspects of FGF21 function in mice have been identified in the context of transgenic overexpression or administration of supraphysiologic doses, rather than in a physiologic setting. Here, we explored the dynamics and function of FGF21 in human volunteers during a 10-day fast. Unlike mice, which show an increase in circulating FGF21 after only 6 hours, human subjects did not have a notable surge in FGF21 until 7 to 10 days of fasting. Moreover, we determined that FGF21 induction was associated with decreased thermogenesis and adiponectin, an observation that directly contrasts with previous reports based on supraphysiologic dosing. Additionally, FGF21 levels increased after ketone induction, demonstrating that endogenous FGF21 does not drive starvation-mediated ketogenesis in humans. Instead, a longitudinal analysis of biologically relevant variables identified serum transaminases--markers of tissue breakdown--as predictors of FGF21. These data establish FGF21 as a fasting-induced hormone in humans and indicate that FGF21 contributes to the late stages of adaptive starvation, when it may regulate the utilization of fuel derived from tissue breakdown.

Introduction Fibroblast growth factor 23 (FGF23), a phosphaturic hormone that suppresses renal 1 α-hydroxylase activity, has been implicated in the development of secondary hyperpara-thyroidism in chronic kidney disease (CKD) [1], [...], Background The relationship between fibroblast growth factor 23 (FGF23) and vitamin D production and catabolism post-renal transplantation has not been characterized. Methods Circulating creatinine, calcium, phosphorus, albumin, parathyroid hormone, FGF23, and 1,25[(OH).sub.2] vitamin D (calcitriol) values were obtained pre-transplantation, daily postoperatively for 5 days, and at 6 months post-transplantation in 44 patients aged 16.4 ± 0.4 years undergoing renal transplantation at UCLA from 1 August 2005 through to 30 April 2007. 25(OH) Vitamin D and 24,25[(OH).sub.2] vitamin D concentrations were obtained at baseline and on post-operative days 5 and 180, and urinary concentrations of creatinine, phosphorus, and FGF23 were measured on post-operative days 1, 3, 5, and 180. Results Circulating phosphate concentrations declined more rapidly and the fractional excretion of phosphorus was higher in the first week post-transplantation in subjects with higher FGF23 values. Fractional excretion of FGF23 was low at all time-points. Circulating 1,25[(OH).sub.2] vitamin D levels rose more rapidly and were consistently higher in patients with lower FGF23 values; however, 25(OH) vitamin D and 24,25[(OH).sub.2] vitamin D values were unrelated to FGF23 concentrations. Conclusions Inhibition of renal 1α-hydroxylase, rather than stimulation of 24-hydroxylase, may primarily contribute to the relationship between FGF23 values and calcitriol. The rapid decline in FGF23 levels post-transplantation in our patient cohort was not mediated solely by the filtration of intact FGF23 by the new kidney. Keywords FGF23 * PTH Vitamin * D Renal transplantation * Phosphorus

Introduction Acute kidney injury (AKI) is considered an independent risk factor for mortality in critically ill children admitted to pediatric intensive care units [1-7]. The current management of these patients [...], Background Acute kidney injury (AKI) increases the morbidity of critically ill children. Thus, it is necessary to identify better renal biomarkers to follow the outcome of these patients. This prospective case-control study explored the clinical value of a urinary biomarker profile comprised of neutrophil gelatinase lipocalin (uNGAL), fibroblast growth factor-2 (uFGF-2), and epidermal growth factor (uEGF) to follow these patients. Methods Urine samples were collected from 21 healthy children, and 39 critically ill children (mean age 7.5 years ± 6.97 SD) admitted to a pediatric intensive care unit with sepsis or requiring extra corporeal membrane oxygenation (ECMO). uNGAL, uFGF-2, and uEGF levels were measured using ELISA kits during the first 24 h of admission to PICU, at peak of illness, and upon resolution of the critical illness. Results On admission, the uNGAL and uFGF-2 levels were increased, and the uEGF levels were decreased, in critically ill children with AKI (n = 19) compared to those without AKI (n = 20), and healthy controls. A biomarker score using the combined cut-off values of uNGAL, uFGF-2, and uEGF (AUC = 0.90) showed the highest specificity to identify children with AKI, relative to each biomarker alone. uNGAL and uFGF-2 on admission showed high sensitivity and specificity to predict mortality (AUC = 0.82). Conclusions The biomarker profile comprised of uNGAL, uFGF-2, and uEGF increased the specificity to detect AKI in critically ill children, when compared to each biomarker used alone. uNGAL and uFGF-2 may also predict the risk of death. Further validation of these findings in a large sample size is warranted. Keywords Acute kidney injury * Neutrophil gelatinase lipocalin (NGAL) * Fibroblast growth factor (FGF-2) * Epidermal growth factor (EGF) * Biomarkers * Sepsis

Introduction Critically ill neonates frequently suffer significant hypoxic and/or ischemic events resulting in multisystem injury, and are at especially high risk for developing acute kidney injury (AKI) [1-3]. Two such [...], Background The goal of this study was to assess the value of a urinary biomarker profile comprised of neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-2 (FGF-2), and epidermal growth factor (EGF), to detect acute kidney injury (AKI) in critically ill neonates. Methods We conducted a prospective cohort pilot study of atrisk neonates treated in a level IIIC neonatal intensive care unit (NICU) with therapeutic hypothermia (HT) (n=25) or extra-corporeal membrane oxygenation (ECMO) (n=10). Urine was collected at baseline, 48 h of illness, and>24 h post-recovery of their corresponding treatments. Control samples were collected from 27 healthy newborns. The data were expressed as urinary concentrations and values normalized for urinary creatinine. AKI was defined as the presence of oliguria > 24 h and/or elevated serum creatinine (SCr), or the failure to improve the estimated creatinine clearance (eCCL) by >50 % post-recovery. Non-parametric statistical tests and ROC analyses were used to interpret the data. Results Fifteen at-risk newborns had AKI. In the first 48 h of illness, the urinary levels of NGAL and FGF-2 had high sensitivity but poor specificity to identify neonates with AKI. At recovery, low urinary EGF levels identified neonates with AKI with a sensitivity of 74 % and specificity of 84 %. Overall, in the early stages of a critical illness, the urinary levels of NGAL and FGF-2 were sensitive, but not specific, to identify neonates at risk of AKI. Low EGF levels post-recovery identified critically ill neonates with AKI. Conclusions These findings require validation in larger prospective studies. Keywords Neonate * Acute kidney injury * Urinary biomarkers * Hypothermia