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Acute renal failure (ARF) is classically defined as a rapid decline in glomerular filtration rate (GFR), leading to accumulation of nitrogenous wastes such as blood urea nitrogen (BUN) and creatinine. ARF is a common condition, associated with serious consequences and unsatisfactory therapeutic options.1-18 Oliguria, defined as a urine output of less than 0.5 ml/kg/hour, is an important clinical sign but occurs in only about half the cases. ARF may be classified as (1) prerenal azotemia, due to a functional response of structurally normal kidneys to hypoperfusion; (2) intrinsic ARF, due to structural damage to the kidneys from prolonged ischemia, nephrotoxins, sepsis, or intrinsic renal disease; and (3) postrenal ARF, due to obstruction of the urinary tract.

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Even the basic definition of ARF is evolving. Acute kidney injury (AKI) is a term recently proposed to reflect the entire spectrum of ARF and is characterized by “an abrupt (within 48 hours) reduction in kidney function defined as an absolute increase in serum creatinine by > 0.3 mg/dl or a relative increase of > 50% from baseline, or oliguria of < 0.5 ml/kg/hour for > 6 hours.”13,14Prerenal azotemia is usually rapidly reversed by restoration of renal perfusion, but early treatment is essential in order to prevent the progression to intrinsic ARF. Once established, there is no effective treatment for ARF, and the clinician can provide only supportive care with dialysis. While the worst outcomes are encountered in patients requiring dialysis, even mild degrees of ARF, such as occurs with only a small increases in serum creatinine, is predictive of an increase in mortality and morbidity rate, irrespective of the underlying cause.19-22 Fortunately, the cellular and molecular tools of modern science are providing critical new insights into the pathogenetic mechanisms and early diagnosis of ARF. Novel strategies that target these pathways hold considerable promise for the prevention and treatment of ARF.

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Pediatric studies from the 1980s and 1990s report hemolytic uremic syndrome, other primary renal causes, and infections as the most prevalent causes leading to acute renal failure (ARF).23 More recent studies in developed countries show a dramatic shift in the epidemiology of ARF such that it is primarily a hospital-acquired illness, with the most common causes being renal ischemia, nephrotoxin use, congenital heart disease, bone marrow transplantation, and sepsis.24,25In contrast, in the undeveloped world of Africa and tropical Asia, children are most likely to develop ARF secondary to gastroenteritis, septicemia, acute glomerulonephritis, or falciparum malaria. Hemolytic uremic syndrome and leptospirosis are common in Latin America, and ARF due to snakebites is often encountered in rural Asia.

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The overall incidence of ARF in adults is reported to be 5% of all hospitalized patients and 30% of patients in intensive care units.9-12 Hospital-acquired pediatric ARF rates are escalating at an alarming rate, over ninefold from the 1980s through 2004.26 The incidence of the most severe forms of ARF, defined by dialysis requirement, ranges from 1% to 2% ...

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