Acute Kidney Injury in Critically Ill Children

__Abstract__ Acute kidney injury (AKI) (previously called acute renal failure) is characterized by the abrupt inability of the kidneys to adequately excrete waste products and regulate fl uid and electrolyte homeostasis appropriately. This results in an at least partially reversible increase in the blood concentration of creatinine and nitrogenous waste products. Renally eliminated medication will accumulate, and nephrotoxic drugs may provide a “second hit” to the already injured kidneys. Furthermore, fl uid management and nutrition will be hampered by oliguria. AKI is typically classifi ed as pre-renal, intrinsically renal, or post-renal. Pre-renal AKI may occur as a consequence of a reduced renal blood fl ow due to several conditions leading to intravascular volume depletion and/or compromised cardiac output. Since the kidneys are intrinsically normal, pre-renal injury is considered reversible once the hemodynamic conditions have been restored to normal. When pre-renal injury persists for a longer period of time, hypoperfusion of the kidneys will lead to hypoxic or ischemic acute tubular necrosis (ATN), a form of intrinsic AKI. During the evolution of pre-renal to intrinsically renal injury several compensatory pathways in the kidney are activated to maintain renal perfusion. These compensatory pathways include intra-renal generation of vasodilatory prostaglandins and angiotensin II, which increases eff erent arteriolar resistance, thereby increasing intraglomerular pressure to maintain or even raise the glomerular fi ltration rate. There are, however, certain clinical circumstances (e.g., administration of cyclo-oxygenase inhibitors, angiotensin converting enzyme inhibitors or nephrotoxic drugs) that may inhibit or interfere with one of the compensatory mechanisms and thus precipitate AKI . In intrinsic AKI, the pathology lies within the kidney itself. In the critically ill patient it is often caused by ATN or interstitial nephritis, elicited by a wide range of drugs or infectious agents. Other causes are glomerulonephritis and hemolytic uremic syndrome. Post-renal AKI is caused by an obstruction of the urinary outfl ow tract such as intraluminal obstruction due to urethral valves or coagulated blood, functional obstruction due to a neurogenic bladder or extraluminal obstruction which may result from malignant conditions. This form of AKI can be restored by removal of the actual obstruction or by insertion of a urinary deviation proximal to the obstruction. Altogether, AKI occurs with variable severity and in many clinical scenarios

Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission

__Introduction__ Children admitted to a pediatric intensive care unit (ICU) are at high risk of developing acute kidney injury (AKI). Although serum creatinine (SCr) levels are used in clinical practice, they are insensitive for early diagnosis of AKI. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (KIM-1) are novel AKI biomarkers whose performance in pediatric ICU patients is largely unknown. In this study, we aimed to characterize uNGAL and KIM-1 patterns in children following ICU admission and to assess their properties in relation to identifying children at risk for AKI development. __Methods__ From June 2010 until January 2014, we conducted a prospective observational cohort study of term-born children ages 1day to 1year on mechanical ventilation. Blood and urine samples were obtained every 6 to 12hours up to 72hours post-admission. Blood samples were assayed for SCr, and urine samples were assayed for uNGAL and KIM-1. The RIFLE (risk, injury, failure, loss, end-stage renal disease) classification as 150%, 200% or 300% of median SCr reference values was used to define AKI. __Results__ A total of 100 children were included (80 survived). Their median age at admission was 27.7days (interquartile range (IQR), 1.5 to 85.5). The median duration of mechanical ventilation was 5.8days (IQR, 3.1 to 11.4). Thirty-five patients had evidence of AKI within the first 48hours post-admission, of whom 24 (69%) already had AKI when they entered the ICU. uNGAL and KIM-1 concentrations in AKI peaked between 6 to 12hours and between 12 to 24hours post-admission, respectively. The maximal area under the receiver operating characteristic curve (AUC) for uNGAL was 0.815 (95% confidence interval (CI), 0.685 to 0.945, P <0.001) at 0 to 6hours post-admission. The discriminative ability of KIM-1 was moderate, with a largest AUC of 0.737 (95% CI, 0.628 to 0.847; P <0.001) at 12 to 24hours post-admission. At the optimal cutoff point (126ng/ml), uNGAL concentration predicted AKI development correctly in 16 (84%) of 19 children, up to 24hours before a rise in SCr became apparent. __Conclusions__ Levels of uNGAL and KIM-1 increase in patients with AKI following ICU admission and peak at 6 to 12hours and 12 to 24hours post-admission, respectively. uNGAL seems to be a reliable marker for identifying children who will develop AKI 24hours later

Acute kidney injury is a frequent complication in critically ill neonates receiving extracorporeal membrane oxygenation: A 14-year cohort study

Introduction: Newborns in need of extracorporeal membrane oxygenation (ECMO) support are at high risk of developing acute kidney injury (AKI). AKI may occur as part of multiple organ failure and can be aggravated by exposure to components of the extracorporeal circuit. AKI necessitates adjustment of dosage of renally eliminated drugs and avoidance of nephrotoxic drugs. We aimed to define systematically the incidence and clinical course of AKI in critically ill neonates receiving ECMO support. Methods: This study reviewed prospectively collected clinical data (including age, diagnosis, ECMO course, and serum creatinine (SCr)) of all ECMO-treated neonates within our institution spanning a 14-year period. AKI was defined by using the Risk, Injury, Failure, Loss of renal function, and End-stage renal disease (RIFLE) classification. SCr data were reviewed per ECMO day and compared with age-specific SCr reference values. Accordingly, patients were assigned to RIFLE categories (Risk, Injury, or Failure as 150%, 200%, or 300% of median SCr reference values). Data are presented as median and interquartile range (IQR) or number and percentage. Results: Of 242 patients included, 179 (74%) survived. Median age at the start o

Proenkephalin as a new biomarker for pediatric acute kidney injury - Reference values and performance in children under one year of age

Acute kidney injury (AKI) is common in critically ill children, but current biomarkers are suboptimal. Proenkephalin A 119-159 (PENK) is a promising new biomarker for AKI in adults, but pediatric data is lacking. We determined PENK reference intervals for healthy children, crucial for clinical implementation, and explored concentrations in critically ill infants aged under 1 year. Observational cohort study in healthy infants and critically ill children aged 0-1 years. Reference values were determined using generalized additive models. Plasma PENK concentrations between healthy children and critically ill children with and without AKI, were compared using linear mixed modelling. The performance of PENK as AKI biomarker was compared to cystatin C (CysC) and β-trace protein (BTP) using receiver-operating-characteristic (ROC) analysis. PENK concentrations in 100 healthy infants were stable during the first year of life (median 517.3 pmol/L). Median PENK concentrations in 91 critically ill children, were significantly higher in those with AKI (n=40) (KDIGO Stage 1 507.9 pmol/L, Stage 2 704.0 pmol/L, Stage 3 930.5 pmol/L) than non-AKI patients (n=51, 432.2 pmol/L) (p < 0.001). PENK appeared to relate better to AKI diagnosis than CysC and BTP (AUROC PENK 0.858, CysC 0.770 and BTP 0.711) in the first 24 h after recruitment. PENK reference values are much higher in young infants than adults, but clearly discriminate between children with and without AKI, with comparable or better performance than CysC and BTP. Our results illustrate the importance of establishing age-normalized reference values and indicate PENK as a promising pediatric AKI biomarker