260 Prognosis of acute kidney injury The prognosis of AKI is highly dependent on the underlying etiology of the AKI. Children who have AKI as a component of multisystem failure have a much higher mortality rate than children with intrinsic renal disease such as HUS, RPGN, and AIN. Recovery from intrinsic renal disease is also highly dependent on the underlying etiology of the AKI. Children with nephrotoxic AKI and hypoxic/ ischemic AKI usually recover normal renal function. In the past it has been thought that such patients are at a low risk for late complications, but several recent studies have demonstrated that chronic kidney disease can evolve from AKI [83–88]. Children who have suffered substantial loss of nephrons, as in HUS or RPGN, are at risk for late development of renal failure long after the initial insult has occurred. Several studies in animal models have docu- mented that hyperfiltration of the remnant nephron may eventually lead to progressive glomerulosclerosis of the remaining nephrons. Thus, children who have had cortical necrosis during the neonatal period and whose renal function has recovered, or children with an episode of severe Henoch–Schönlein purpura or HUS, are clearly at risk for the late development of renal complications. Such children need life-long monitoring of their renal function and blood pressure, and life-long urinalyses. As described above, it has been thought that acute kidney injury due to hypoxic/ischemic and nephrotoxic insults were reversible, with a return of renal function to normal. However, recent studies have demonstrated that hypoxic/ischemic and nephrotoxic insults can lead to physiologic and morphologic alterations in the kidney that may lead to kidney disease at a later time [50]. Studies of adults demonstrate that CKD may evolve from AKI [83, 84]. Thus, acute kidney injury from any cause can be a concern for later kidney disease. Importantly, acute kidney injury is likely to be especially deleterious when the kidney has not yet grown to adult size and/or before the full complement of nephrons have developed. Since nephro- genesis is not complete until approximately 34 weeks’ gestation, acute kidney injury during this interval might lead to a decreased number of nephrons, and, indeed, studies have suggested that acute kidney injury during nephrogenesis results in decreased numbers of nephrons and subsequent glomerulomegaly [86]. Acute kidney injury in the full-term neonate is also associated with later kidney disease [88]. In one study of six older children with a history of AKI not requiring dialysis in the neonatal period, only two were healthy, three had chronic renal failure and one was on dialysis. Studies on older children have also shown that AKI leads to CKD in a higher percentage of children than was previously appreciated [85]. In a prospective study of renal insufficiency in children under- Pediatr Nephrol (2009) 24:253–263 going bone marrow transplantation, the incidence of acute renal insufficiency was high and was predictive of chronic renal insufficiency. Of those who survived, 11% developed chronic kidney disease, and AKI was the sole predictor of chronic kidney disease [89]. Thus, children with a history of AKI from any cause need long-term follow-up. Questions (answers appear following the reference list) 1. Epidemiology studies of AKI in children has shown that a. the incidence of AKI is decreasing: true or false b. genetic factors may play a role in the susceptibility to AKI: true or false c. hypoxic/ischemic AKI is a rare cause of AKI in children: true or false d. nonsteroidal anti-inflammatory therapy is a risk factor for AKI in newborns: true or false 2. Diagnosis and etiology of AKI in children a. the definition of AKI in children is well established: true or false b. the serum creatinine is a sensitive marker of AKI: true or false c. in utero exposure to ACE inhibitors is associated with AKI in neonates: true or false d. AKI in hospitalized children may be the result of multiple etiologies: true or false e. urinary sodium concentration is a reliable indicator of pre-renal versus hypoxic/ischemic AKI in pre- mature newborns: true or false 3. Hypoxic/ischemic AKI a. alterations in blood flow are not thought to play a role in hypoxic/ischemic AKI: true or false b. reactive oxygen molecules generated by activated PMNs may play a role in hypoxic/ischemic ATN: true or false c. ATP depletion is an early response to hypoxic/ ischemic AKI: true or false d. hypoxic/ischemic AKI is always reversible and has no long-term consequences: true or false 4. Management of AKI in children a. diuretic therapy in AKI shortens hospital stay, decreases the need for dialysis therapy and decreases mortality rates: true or false b. ‘renal-dose’ dopamine therapy has not been shown to be effective in adult patients: true or false c. prevention of AKI is important on a global scale in lowering the number of deaths from AKI: true or false