SummaryBackground and objectives Fibroblast growth factor 23 plays an important role in regulating phosphate and vitamin D homeostasis. Elevated levels of fibroblast growth factor 23 are independently associated with mortality in patients with CKD and ESRD. Whether fibroblast growth factor 23 levels are elevated and associated with adverse outcomes in patients with AKI has not been studied.Design, setting, participants, & measurements This study had 30 participants with AKI, which was defined as an increase in serum creatinine$0.3 mg/dl or $50% from baseline, and 30 controls from the general hospital wards and intensive care units. Plasma levels of C-terminal fibroblast growth factor 23 and vitamin D metabolites were measured within 24 hours of AKI onset and 5 days later. The composite endpoint was death or need for renal replacement therapy.Results Enrollment fibroblast growth factor 23 levels were significantly higher among participants with AKI than controls (median [interquartile range]=1471 [224-2534] versus 263 [96-574] RU/ml, P=0.003). Enrollment fibroblast growth factor 23 correlated negatively with 25-hydroxyvitamin D (r=20.43, P,0.001) and 1,25-dihydroxyvitamin D (r=20.39, P=0.003) and positively with phosphate (r=0.32, P=0.02) and parathyroid hormone (r=0.37, P=0.005). Among participants with AKI, enrollment fibroblast growth factor 23 (but not other serum parameters) was significantly associated with the composite endpoint, even after adjusting for age and enrollment serum creatinine (11 events; adjusted odds ratio per 1 SD higher ln[fibroblast growth factor 23]=13.73, 95% confidence interval=1.75-107.50).Conclusions Among patients with AKI, fibroblast growth factor 23 levels are elevated and associated with greater risk of death or need for renal replacement therapy.

OBJECTIVES Early thrombosis (ET) contributes to autogenous arteriovenous fistula (AVF) failure. We studied patients undergoing AVF placement in the Hemodialysis Fistula Maturation (HFM) Study, a prospective, observational cohort study, using a nested case-control analysis to identify pre-operative and intra-operative predictors of ET. METHODS ET cases were compared to controls who were matched on gender, age, diabetes, dialysis status, and surgeon fistula volume. ET was defined as thrombosis diagnosed by physical exam or ultrasound within 18 days of AVF creation. Conditional logistic regression models were fit to identify risk factors for ET. RESULTS Thirty-two ET cases (5.3%) occurred among 602 study participants; 198 controls were matched. ET was associated with female gender (OR=2.75, CI 1.19–6.38, P=0.018), fistula location (forearm vs. upper arm) (OR=2.76, CI 1.05–7.23, P=0.039), feeding artery (radial vs. brachial) (OR=2.64, CI 1.03–6.77, P=0.043) and arterial diameter (OR=1.52, CI 1.02–2.26, P=0.039, per mm smaller). Draining vein diameter was nonlinearly associated with ET, with highest risk in 2–3 mm veins. Surprisingly, ET risk was lower in diabetics (OR=0.19, CI 0.07–0.47, P=0.0004), lower with less nitroglycerin-mediated brachial artery dilatation (NMD%) (OR=0.42, CI 0.20–1.92, P=0.029 for each 10% lower) and higher with lower carotid-femoral pulse wave velocity (OR=1.49, CI 1.02–2.20, P=0.041, for each m/sec lower). Intraoperative protamine use was associated with a higher ET risk (OR 3.26, CI 1.28-∞, P=0.038). Surgeon’s intraoperative perceptions were associated with ET: surgeons’ greater concern about maturation success (likely, marginal, unlikely) was associated with higher thrombosis risk (OR 8.09, CI 4.03-∞, p<0.0001, per category change), as were absence vs. presence of intraoperative thrill (OR 21.0, CI 5.07-∞, P=0.0002) and surgeons’ reported frustration during surgery (OR 6.85, CI 2.70-∞, P=0.0004). Reduced extent of intraoperative thrill (proximal, mid or distal third of the forearm or upper arm, based on AVF placement) was also associated with ET (OR 2.91, CI 1.31-∞, P=0.014, per diminished level). Oral antithrombotic medication use was not significantly associated with ET. CONCLUSIONS ET was found to be associated with female gender, forearm AVF, smaller arterial size, draining vein diameter of 2–3 mm, and protamine use. Paradoxically, diabetes and stiff, noncompliant feeding arteries were associated with lower frequency of ET. Absent or attenuated intraoperative thrill, and both surgeon frustration and concern about successful maturation during surgery, were strongly correlated with ET.

Multiple processes of care and complications are associated with AVF maturation outcomes.

Objective Numerous studies have evaluated the prevalence and importance of vitamin D deficiency among patients with chronic kidney disease and end-stage renal disease, however, little is known about vitamin D levels in acute kidney injury (AKI). We evaluated the association between vitamin D metabolites and clinical outcomes among patients with AKI. Design Prospective cohort study. Patients 30 participants with AKI and 30 controls from general hospital wards and intensive care units at a tertiary care hospital. Measurements Plasma levels of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], 24R,25-dihydroxyvitamin D3, vitamin D binding protein (VDBP), and fibroblast growth factor 23 (FGF23) were measured within 24 hours of AKI onset and 5 days later. Bioavailable 25(OH)D and 1,25(OH)2D levels, defined as the sum of free- and albumin-bound 25(OH)D and 1,25(OH)2D, were estimated using equations. Results Compared to controls, participants with AKI had lower levels of 1,25(OH)2D [17 (10-22) versus 25 (15-35) pg/ml, p=0.01], lower levels of VDBP [23 (15-31) versus 29 (25-36) mg/dl, p=0.003], and similar levels of bioavailable 25(OH)D and 1,25(OH)2D at enrollment. Levels of bioavailable 25(OH)D were inversely associated with severity of sepsis in the overall sample (p<0.001). Among participants with AKI, bioavailable 25(OH)D, but not other vitamin D metabolites, was significantly associated with mortality after adjusting for age and serum creatinine (adjusted odds ratio per 1 SD ln [bioavailable 25(OH)D]=0.16, 95% confidence interval=0.03 to 0.85). Conclusions Bioavailable 25(OH)D could have a role as a biomarker or mediator of adverse outcomes among patients with established AKI.

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Supplemental 5% albumin solution given to maintain CVP values of >8 mm Hg prevented sodium and fluid losses but did not have an impact on blood volume in our patients, who were hypervolemic in base line measurements. The natriuresis that occurs after SAH may be mediated in part by elevations of GFR. In addition to acting as a colloid volume expander, 5% albumin solution lowers the GFR and promotes renal sodium retention after SAH. These properties may limit the amount of total fluid required to maintain a given CVP value and hence may minimize the frequency of pulmonary edema.

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Rhabdomyolysis-induced acute kidney injury (AKI) is characterized by hyperphosphataemia and hypocalcaemia. Despite appropriate secondary elevation of parathyroid hormone (PTH) in response to hypocalcaemia, rhabdomyolysis and AKI are associated with acute deficiency of 1,25-dihydroxycholecalciferol (1,25(OH)(2)D(3)), and yet, the mechanism responsible for such a deficiency remains unclear. Fibroblast growth factor 23 (FGF-23), a potent phosphaturic hormone that inhibits 25-hydroxyvitamin D(3)-1alpha-hydroxylase, could explain the deficiency of 1,25(OH)(2)D(3) in this setting. Here, we document, for the first time, elevated levels of FGF-23 in a patient with rhabdomyolysis-induced AKI.