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 %).

Cardiac calcifications are more prevalent in children receiving hemodialysis than peritoneal dialysis.

BACKGROUND: Children receiving maintenance dialysis exhibit high cardiovascular (CV) associated mortality. We and others have shown high prevalence of cardiac calcifications (CC) in children with endstage renal disease (ESRD). However, no pediatric study has examined modality difference in CC prevalence. The current study was conducted to assess for a difference in CC prevalence between hemodialysis (HD) and peritoneal dialysis (PD) in children with ESRD. METHODS: 38 patients (19 female, 19 male; mean age 15.5 ± 4.1 years) receiving dialysis (21 HD, 17 PD) were included in the study. CC were assessed by ultrafast gated CT and quantified by Agatston score. Patients received thrice weekly HD for 3 - 3.5 hours or daily continuous cycler PD (CCPD). FGF 23, IL-6, IL-8, and CRP levels were obtained at time of CT. Time-averaged (6 months prior to CT) serum Ca, P, Alb, iPTH, and cholesterol levels were obtained. Patients on aspirin, with evidence of infection, underlying collagen vascular disease were excluded. RESULTS: CC were present in 11/38 patients, but more prevalent in HD vs. PD (9/21 vs. 2/17, p = 0.04). Subjects with CC were older (p = 0.0003), had longer dialysis vintage (p = 0.02) and higher serum phosphorus (p = 0.02) and FGF 23 levels (p = 0.03). HD patients also had significantly higher phosphorus (p = 0.02), FGF 23 (p = 0.009), and IL-8 levels (p = 0.02) when compared to PD patients. Residual renal function was not different between modalities or patients with CC. On a multinomial regression model, modality, and age remained independent associations for CC prevalence. CONCLUSION: We have shown that pediatric patients receiving CCPD have lower CC prevalence conferring lower CV risk. The better control of mineral imbalance in patients receiving PD may play an important role in lower CC prevalence.

Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children.

Reliable prediction of severe acute kidney injury (AKI) has the potential to optimize treatment. Here we operationalized the empiric concept of renal angina with a renal angina index (RAI) and determined the predictive performance of RAI. This was assessed on admission to the pediatric intensive care unit, for subsequent severe AKI (over 200% rise in serum creatinine) 72 h later (Day-3 AKI). In a multicenter four cohort appraisal (one derivation and three validation), incidence rates for a Day 0 RAI of 8 or more were 15-68% and Day-3 AKI was 13-21%. In all cohorts, Day-3 AKI rates were higher in patients with an RAI of 8 or more with the area under the curve of RAI for predicting Day-3 AKI of 0.74-0.81. An RAI under 8 had high negative predictive values (92-99%) for Day-3 AKI. RAI outperformed traditional markers of pediatric severity of illness (Pediatric Risk of Mortality-II) and AKI risk factors alone for prediction of Day-3 AKI. Additionally, the RAI outperformed all KDIGO stages for prediction of Day-3 AKI. Thus, we operationalized the renal angina concept by deriving and validating the RAI for prediction of subsequent severe AKI. The RAI provides a clinically feasible and applicable methodology to identify critically ill children at risk of severe AKI lasting beyond functional injury. The RAI may potentially reduce capricious AKI biomarker use by identifying patients in whom further testing would be most beneficial.

Electronic health record identification of nephrotoxin exposure and associated acute kidney injury.

BACKGROUND AND OBJECTIVE: Nephrotoxic medication exposure represents a common cause of acute kidney injury (nephrotoxin-AKI) in hospitalized children. Systematic serum creatinine (SCr) screening has not been routinely performed in children receiving nephrotoxins, potentially leading to underestimating nephrotoxin-AKI rates. We aimed to accurately determine nephrotoxin exposure and nephrotoxin-AKI rates to drive appropriate interventions in non-critically ill hospitalized children. METHODS: We conducted a prospective quality improvement project implementing a systematic electronic health record (EHR) screening and decision support process (trigger) at a single quaternary pediatric hospital. Patients were all noncritically ill hospitalized children receiving an intravenous aminoglycoside for ≥3 days or ≥3 nephrotoxins simultaneously (exposure). Pharmacists recommended daily SCr monitoring in exposed patients. AKI was defined by the modified pediatric Risk, Injury, Failure, Loss and End-stage Renal Disease criteria (≥25% decrease in estimated creatinine clearance). We developed 4 novel metrics: exposure rate per 1000 patient-days, AKI rate per 1000 patient-days, AKI rate (%) per high nephrotoxin admission, and AKI days per 100 exposure days (AKI intensity). RESULTS: This study included 21 807 patients accounting for 27 711 admissions. A total of 726 (3.3%) unique exposed patients accounted for 945 hospital admissions (6713 patient-days). AKI occurred in 25% of unique exposed patients and 31% of exposure admissions (1974 patient-days). Our EHR-driven SCr nephrotoxin-AKI surveillance process was associated with a 42% reduction in AKI intensity. CONCLUSIONS: Nephrotoxin-AKI rates are high in noncritically ill children; systematic screening for nephrotoxic medication exposure and AKI detection was accomplished reliably through an EHR based trigger tool.