syndrome at DCM diagnosis conferred an increased risk of 5-year mortality (hazard ratio, 2.4; 95% confidence interval, 0.8 to 7.4), and the estimated glomerular filtration rate was positively correlated with measures of ventricular function Thus these preliminary studies suggest careful attention should be paid to kidney function in children with acute cardiac dysfunction The management of AKI in heart failure has also been the subject of intense clinical study over the past decade in adults, with a focus on diuretic administration versus mechanical fluid removal via ultrafiltration.64,65 While this focus has generated randomized clinical trials comparing diuretics to ultrafiltration with varying results, a potentially more thoughtful approach is to consider diuretics as a first line of treatment and then escalation to ultrafiltration in patients who are resistant to diuretics Patients with heart failure may have AKI from a functional, prerenal cause, from structural intrinsic renal damage, or both.66 Patients with functional AKI may respond well to diuretics if renal perfusion and oncotic pressure are sufficient, whereas patients with structural AKI may not respond well The additional information provided by structural AKI biomarkers in the acute heart failure setting has been recently addressed First, one meta-analysis of pediatric and adult studies demonstrated that 41% of patients with elevated NGAL levels would have had the AKI diagnosis missed by serum creatinine alone, and patients with NGAL+/Cr− AKI has similar morbidity and mortality as patients with NGAL−/SCr+ AKI.67 Second, a prospective adult study revealed that integration of a heart failure marker (B-type natriuretic peptide) and a kidney damage marker (plasma NGAL) improved the prediction of 30-day mortality and hospital readmission rates.68 Finally, in the chronic cardiomyopathy setting, the urinary biomarkers interleukin-18, kidney injury molecule-1, and NGAL were observed in higher concentrations than in healthy matched controls.69 In addition, a combined model using cut-off values of kidney injury molecule-1 of 235 or greater, interleukin-18 of 17.5 or greater, and B-type natriuretic peptide of 15 pg/mL resulted in differentiation of patients with mildly depressed LV (55% > LV ejection fraction ≥45%) and those with a left ventricular ejection fraction less than 45% Summary The complex interplay between clinically apparent heart and kidney dysfunction, as well as subclinical injury detected by novel biomarkers, and the association with increased morbidity and mortality represent an area in cardiology that demands more intense research focus The existence of these associations in children, including the chronic renal consequences of heart disease, validates the concept in the absence of multiple chronic comorbidities that are ubiquitous in adults Enhanced risk stratification, earlier targeted interventions, and systematic follow-up of patients for the development of kidney disease have the potential to improve the immediate and long-term patient outcomes Annotated References Kidney Disease: Improving Global Outcomes (KDIGO) Acute kidney injury work group: KDIGO clinical practice guideline for acute kidney injury Kidney Int 2012;suppl(2):1–138 The KDIGO criteria represent the current standard for diagnosis of AKI development and severity AKI by these criteria have repeatedly demonstrated independent associations between stage 2 or 3 AKI and morbidity and mortality in pediatric populations, including children who develop AKI after cardiac surgery Blinder JJ, Goldstein SL, Lee VV, et al Congenital heart surgery in infants: effects of acute kidney injury on outcomes J Thorac Cardiovasc Surg 2012;143(2):368–374 This retrospective study of more than 400 infants after cardiac surgery assessed for associations between AKI development and severity and outcomes Stage 2 or 3 AKI was independently associated with patient mortality, prolonged mechanical ventilation, the need for inotropic support and ventricular dysfunction (30 days postoperatively) In multivariable analysis, stage 2 or 3 AKI conferred a greater risk of mortality ... as well as subclinical injury detected by novel biomarkers, and the association with increased morbidity and mortality represent an area in cardiology that demands more intense research focus The existence of these associations in children, including the chronic renal consequences of heart disease, validates the... AKI by these criteria have repeatedly demonstrated independent associations between stage 2 or 3 AKI and morbidity and mortality in pediatric populations, including children who develop AKI after cardiac surgery Blinder JJ, Goldstein SL, Lee VV, et al