258 [55]. Rasburicase has been shown to be effective and well tolerated in the prevention of renal failure in pediatric patients with tumor lysis syndrome [55]. AKI during tumor lysis syndrome can also result from extreme hyperphos- phatemia from rapid breakdown of tumor cells and the precipitation of calcium phosphate crystals [56]. Acute interstitial nephritis Acute interstitial nephritis (AIN) may cause renal failure as a result of a reaction to a drug or due to idiopathic AIN. Children with AIN may have rash, fever, arthralgias, eosinophilia, and pyuria with or without eosinophiluria. Medications commonly associated with AIN include methicillin and other penicillin analogs, cimetidine, sulfo- namides, rifampin, nonsteroidal anti-inflammatory drugs, and proton pump inhibitors, whereas other drugs have been associated with AIN less commonly [57]. AIN associated with nonsteroidal anti-inflammatory drugs may also present with high-grade proteinuria and nephrotic syndrome. Specific therapy for AIN includes withdrawal of the drug implicated in causing the AIN. In addition, corticosteroids may aid in the resolution of the renal failure [57]. Rapidly progressive glomerulonephritis Any form of glomerulonephritis in its most severe degree can present with AKI and RPGN. The clinical features include hypertension, edema, hematuria that is frequently gross, and a rapidly rising levels of blood urea nitrogen (BUN) and creatinine. The characteristic pathological finding in RPGN is extensive crescent formation. RPGN due to postinfectious glomerulonephritis typically does not lead to CKD, while other glomerulonephritides, such as antineutrophil cytoplasmic antibody (ANCA)-positive glo- merulonephritis, Goodpasture’s syndrome, and idiopathic RPGN, typically present with AKI and may quickly evolve into CKD, with or without therapy. Serological tests including an antinuclear antibody (ANA), ANCA, anti– glomerular basement membrane (GBM) titers, and comple- ment studies are required to evaluate the etiology of the RPGN. Because specific therapy will depend on the pathological findings, a biopsy should be performed relatively quickly when a child presents with clinical characteristics suggestive of RPGN. Vascular insults Cortical necrosis as a cause of AKI is much more common in young children, particularly in neonates. Cortical necrosis is associated with hypoxic/ischemic insults due to perinatal anoxia, placenta abruption, and twin–twin or twin–mother transfusions, with resultant activation of the Pediatr Nephrol (2009) 24:253–263 coagulation cascade. Children and newborns with cortical necrosis usually have gross or microscopic hematuria and oliguria and may have hypertension as well. In addition to laboratory features of elevated levels of BUN and creatinine, thrombocytopenia may also be present, due to the microvas- cular injury. Radiographic features include normal findings of renal ultrasound in the early phase, and ultrasound in the later phases may show that the kidney has undergone atrophy and has substantially decreased in size. The prognosis for cortical necrosis is much worse than that for ATN. Children with cortical necrosis may partially recovery or not recover at all. HUS is a common cause of AKI in children and leads to substantial morbidity and mortality rates and long-term complications that may not become apparent until adulthood [58]. While an important cause of AKI in children, HUS will not be further discussed here, as a review of HUS has recently been published [58]. Obstructive uropathy Obstruction of the urinary tract can cause acute kidney injury if the obstruction occurs in a solitary kidney, if it involves the ureters bilaterally, or if there is urethral obstruction. Obstruc- tion can result from congenital malformations such as posterior urethral valves, bilateral ureteropelvic junction obstruction or bilateral obstructive ureteroceles. Acquired urinary tract obstruction can result from passage of kidney stones or, rarely, from tumors. It is important to evaluate for obstruction, since the management is to relieve the obstruction promptly. Management of acute kidney injury in children Preventive measures Two studies from different geographic regions of Nigeria demonstrated that the most common cause of AKI in children was volume depletion and that the AKI was due to preventable cause [59, 60]. Since dialytic resources were scare, the mortality rate in these studies was quite high [59, 60]. Thus, on a global scale, the prevention of AKI is likely to have a larger impact on mortality rates than other measures. Intravenous infusion of theophylline, given to severely asphyxiated neonates within the first hour of birth, was associated with improved fluid balance, creatinine clearance, and reduced serum creatinine levels and had no effects on neurological and respiratory complications [61–63]. Adenosine is a potent vasoconstrictor that is released from the catabolism of ATP during ischemia; the potential mechanisms that theophylline could protect from AKI could be the blocking of the adenosine receptor. Other studies of asphyxiated