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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 ...