Early prediction of pediatric acute kidney injury from the emergency department: A pilot study.

BACKGROUND: Identifying acute kidney injury (AKI) early can inform medical decisions key to mitigation of injury. An AKI risk stratification tool, the renal angina index (RAI), has proven better than creatinine changes alone at predicting AKI in critically ill children. OBJECTIVE: To derive and test performance of an "acute" RAI (aRAI) in the Emergency Department (ED) for prediction of inpatient AKI and to evaluate the added yield of urinary AKI biomarkers. METHODS: Study of pediatric ED patients with sepsis admitted and followed for 72 h. The primary outcome was inpatient AKI defined by a creatinine >1.5× baseline, 24-72 h after admission. Patients were denoted renal angina positive (RA+) for an aRAI score above a population derived cut-off. Test characteristics evaluated predictive performance of the aRAI compared to changes in creatinine and incorporation of 4 urinary biomarkers in the context of renal angina were assessed. RESULTS: 118 eligible subjects were enrolled. Mean age was 7.8 ± 6.4 years, 16% required intensive care admission. In the ED, 27% had a +RAI (22% had a >50% creatinine increase). The aRAI had an AUC of 0.92 (0.86-0.98) for prediction of inpatient AKI. For AKI prediction, RA+ demonstrated a sensitivity of 94% (69-99) and a negative predictive value of 99% (92-100) (versus sensitivity 59% (33-82) and NPV 93% (89-96) for creatinine ≥2× baseline). Biomarker analysis revealed a higher AUC for aRAI alone than any individual biomarker. CONCLUSIONS: This pilot study finds the aRAI to be a sensitive ED-based tool for ruling out the development of in-hospital AKI.

Pre-operative level of FGF23 predicts severe acute kidney injury after heart surgery in children.

BACKGROUND: Early detection of acute kidney injury (AKI) after cardiac surgery has improved recently with the discovery and validation of novel urinary biomarkers. However, objective tools to predict the risk of AKI before the insult are still missing. We tested the hypothesis that pre-operative serum fibroblast growth factor 23 (FGF23) concentrations would be elevated in children who develop AKI after heart surgery with cardiopulmonary bypass (CPB). We also compared post-operative FGF23 concentrations to other biomarkers for early detection of AKI. METHODS: Blood and urine samples were collected in a prospective observational study from 83 children with congenital heart disease. Severe AKI (sAKI) development (KDIGO stages II-III) in the first seven days after surgery was the primary outcome. RESULTS: Thirty of 76 (39.5%) and 11/76 (14.5%) of patients developed AKI and sAKI, respectively. Pre-operative serum creatinine, cystatin C, and urine biomarker concentrations did not differ between sAKI patients and controls. Pre-operative serum FGF23 levels were higher in patients who developed sAKI (median [IQR] value of 819 RU/ml [397.7, 1196.8] vs. 324.3 RU/ml [124.6, 679.8] (p = 0.02). FGF23 12-24 h after the termination of CPB was also associated with sAKI in the first week after surgery (498 RU/ml [226, 928] vs. 1435 RU/ml [831, 12,996]). CONCLUSIONS: Pre- and post-operative FGF23 levels are higher in children who develop sAKI after cardiac surgery. We suggest FGF23 may be able to detect sub-clinical kidney injury and can be used with demographic AKI risk factors to enhance post-operative sAKI risk prediction.

Early postoperative measurement of fibroblast growth factor 23 predicts severe acute kidney injury in infants after cardiac surgery
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AIMS: Acute kidney injury (AKI) occurs in 30 - 40% of children after cardiac surgery (CS) and is associated with poor prognosis. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone with a pivotal role in phosphorus and vitamin D metabolism. We assessed FGF23 as an early marker for severe AKI (sAKI) in infants after CS. MATERIALS AND METHODS: Samples were previously collected in a multicenter observational study from children after CS. Serum FGF23 (n = 41) and urine AKI biomarker levels (n = 35) were assessed 4 - 8 hours after bypass. sAKI was defined as ≥ 100% rise in serum creatinine over baseline. Non-parametric and ROC analyses were used to evaluate the association between FGF23, urine AKI markers, and sAKI in the week after CS. RESULTS: Serum FGF23, urine NGAL, and urine KIM1 were higher in sAKI patients. The AUC-ROC for urine NGAL (0.74, [0.49 - 0.99]), urine KIM1 (0.79, [0.68 - 0.98]), and serum FGF23 (0.74, [0.5 - 0.9]) showed fair prediction of sAKI. CONCLUSION: Early measurement of FGF23 has predictive ability in infants who develop sAKI after CS with cardiopulmonary bypass.
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Novel urinary tubular injury markers reveal an evidence of underlying kidney injury in children with reduced left ventricular systolic function: a pilot study.

BACKGROUND: Evolving data suggest tubular injury markers (TIM) to be diagnostic and prognostic biomarkers of kidney injury in adults with chronic cardiac dysfunction. Such data are not well delineated in asymptomatic children with cardiomyopathy. This study sought to evaluate kidney involvement in children with left ventricular (LV) systolic dysfunction. METHODS: We conducted a cross-sectional case-control study in 61 asymptomatic children (aged 1.7-21.9 years) with dilated cardiomyopathy (DCM) and LV ejection fraction (LVEF) < 55 %. Routine conventional kidney function markers and the following urinary TIM were measured: KIM-1, IL-18, neutrophil gelatinase-associated lipocalin (NGAL), and L-FABP. Characteristics and TIM data of cases were compared with those of 61 age- and gender-matched healthy controls. RESULTS: Children with DCM had higher TIM concentrations compared with controls for IL-18 (28.2 pg/mg, IQR [15.9-42.5] vs19.0 [12.6-28.6], p < 0.001), NGAL (13.2 ng/mg [6.5-44.3] vs 8.3 [3.1-17.5], p = 0.01), and KIM-1 (386 pg/mg (248-597) vs 307 [182-432], p = 0.02). All conventional kidney function markers were within normal limits in the DCM cohort. A combined model using cut-off values of KIM-1 ≥ 235, IL-18 ≥ 17.5, and (BNP) > 15 pg/ml resulted in distinction between patients with mildly depressed LV (55 > LVEF ≥ 45) and those with LVEF < 45 %. The sensitivity of this model was ≥80 % when any of the cut-off values was met and specificity 83 % when all cut-off values were met. CONCLUSIONS: Our data suggest that asymptomatic children with LVEF < 55 % might have subclinical kidney injury that cannot be detected with conventional kidney function markers. TIM in conjunction with other cardiac function markers may be utilized to distinguish asymptomatic children with DCM and moderate or worse LV dysfunction (LFEV < 45 %) from those with mild LV dysfunction (55 > LVEF ≥ 45 %).