254 Type Pre-renal injury Intrinsic renal disease Table 1 Etiology of common causes of acute kidney injury Obstructive uropathy with acute interstitial nephritis, nephrotoxic renal insults including aminoglycoside nephrotoxicity, and contrast nephropathy are more likely to have AKI with normal urine output. The morbidity and mortality rates of non- oliguric AKI are less than those of oliguric renal failure [1–5]. This review will discuss the epidemiology of AKI, the common causes of AKI, the pathophysiology of hypoxia/ischemia-induced AKI, the new aspect of manage- ment of AKI, and potential future therapies for AKI. This review will not address fluid and electrolyte management, nutritional therapy, or renal replacement therapy for AKI, as these aspects of AKI will be the topics of forthcoming reviews. Epidemiology of acute kidney injury While the precise incidence and causes of AKI in pediatric patients is unknown, recent studies suggest that the incidence of AKI in hospitalized children is increasing [1–10]. An important cause of AKI in hospitalized children is in the setting of post-cardiac surgery and in children undergoing stem cell transplantation. AKI in such children is frequently Etiology Decreased true intravascular volume Decreased effective intravascular volume Acute tubular necrosis (vasomotor nephropathy) Hypoxic/ischemic insults Drug induced Toxin mediated Endogenous toxins—hemoglobin, myoglobin Exogenous toxins—ethylene glycol, methanol Uric acid nephropathy and tumor lysis syndrome Interstitial nephritis Drug induced Idiopathic Glomerulonephritis—RPGN Vascular lesions Renal artery thrombosis Renal vein thrombosis Cortical necrosis Hemolytic uremic syndrome Hypoplasia/dysplasia with or without obstructive uropathy Idiopathic Exposure to nephrotoxic drugs in utero Obstruction in a solitary kidney Bilateral ureteral obstruction Urethral obstruction Pediatr Nephrol (2009) 24:253–263 multifactorial, with ischemic/hypoxic injury and nephrotoxic insults being important contributors; the pathophysiology of hypoxic ischemic injury and nephrotoxic insults are descried below. No epidemiology studies using an established definition of AKI have been conducted in pediatric patients. As described below, in pre-renal AKI the kidney is intrinsically normal, and renal function promptly returns to normal with restoration of adequate renal perfusion, while, in acute tubular necrosis, the kidney has sustained intrinsic injury which requires repair and recovery before renal function returns to normal. In a large study of adult patients, the incidence of AKI was 209 per million population, and the most common cause of AKI was pre-renal in 21% of patients and acute tubular necrosis in 45% of patients [11]. Similar epidemiologic studies have not been performed in pediatric patients, but hypoxia/ischemia- and nephrotoxin- induced AKI have been shown to be important causes of AKI in neonates, children and adolescents [1–10]. In a study of pediatric patients in a tertiary care center, 227 children received dialysis during an 8-year interval for an overall incidence of 0.8 per 100,000 total population [2]. In a study of neonates, the incidence of AKI ranged from 8% to 24% of newborns, and AKI was particularly common in neonates who had undergone cardiac surgery [3, 10]. Neonates with severe asphyxia had a higher incidence of AKI, while neonates with moderate asphyxia developed AKI less often [3, 7, 8]. Other studies have demonstrated that very low birth weight (less than 1,500 g), a low Apgar score, a patent ductus arteriosus and maternal receipt of antibiotics and nonsteroidal anti-inflammatory drugs was associated with the development of AKI [6]. A low Apgar score and maternal ingestion of nonsteroidal anti-inflammatory drugs has been associated with decreased renal function in preterm infants [6, 12]. The incidence of AKI in newborns in a developing country was 3.9/1,000 live births and 34.5/1,000 newborns admitted to the neonatal unit [7]. Several studies have demonstrated that, in addition to environmental factors, there may be genetic risk factors for AKI in some newborns and children. Several candidate polymorphisms have not been shown to be associated with AKI, while other polymorphisms have been found to be associated with AKI. Polymorphism of the angiotensin- converting enzyme (ACE) gene or the angiotensin receptor gene, with resultant alterations in activity of the renin– angiotensin system, does not appear to play a role in the development of AKI [13]. In studies of newborns, poly- morphisms of tumor necrosis factor alpha, interleukin 1b, interleukin 6 and interleukin 10 genes were investigated to determine if polymorphisms of these genes would lead to a more intense inflammatory response and predispose newborns to AKI [14]. The allelic frequency of the individual genes did not differ between newborns with AKI and those without AKI, but the TNFa/IL-6 AG/GC