Acute renal failure
DR AQEEL ALGHAMDI
MBBS,DCH,JBCP,ABP,FBN
consultant pediatric nephrology
Acute renal failure
Acute kidney injury (AKI) is defined as the
abrupt loss of kidney function that results in
1 ) a decline in glomerular filtration rate (GFR),
2 ) retention of urea and other nitrogenous
waste products,
3 ) dysregulation of extracellular volume and
electrolytes
AKI is manifested by increases
in nitrogenous waste products (BUN) and serum
creatinine,
and, in some cases, a concomitant reduction in
urine output (less than 0.5 to 1 mL/kg per hour
CLASSIFICATION
pRIFLE — pRIFLE is a pediatric modification of
the adult RIFLE classification and consists of
three graded levels of injury (Risk, Injury, and
Failure) based upon the magnitude of change in
estimated GFR (eg, changes in serum creatinine)
or urine output,
and two outcome measures (Loss of kidney
function and End-stage renal disease)
CLASSIFICATION
Pediatric RIFLE Classification of acute kidney injury
pRIFLE stage Estimated creatinine clearance (eCCl)
Urine output
R = Risk for renal dysfunction eCCl decreased by 25%
<0.5 mL/kg per hour for 8 h
I = Injury to the kidney eCCl decreased by 50 % <0.5
mL/kg per hour for 16 h
F = Failure of kidney function eCCl decreased by 75 %
or eCCl <35 mL/min per 1.73 m2 <0.3 mL/kg per hour
for 24 h or anuria for 12 h
L = Loss of kidney function Persistent failure >4 weeks
E = End-stage renal disease Persistent failure >3 months
GFR
Glomerular filtration rate estimate by Schwartz
formula
Glomerular filtration rate = k * Height /
Serumcreatinine
uop
Anuria, no urine output
•Oliguria defined as urine output <1 mL/kg per hour in
infants, and in children and adults, urine output <0.5 mL/kg
per hour for greater than six hours
•Nonoliguria – The majority of neonates with AKI will have
nonoliguric AKI, even those with moderate to severe
impairment of kidney function
•Polyuria – Some patients with a urinary concentrating defect
will present with polyuric AKI, particularly those with acute
tubular necrosis
Causes and mechanisms
Vascular – Blood from the renal arteries is delivered
to the glomeruli. Interruption of perfusion to the
kidneys results in prerenal AKI.
●Glomeruli – Ultrafiltration occurs at the glomeruli
forming an ultrafiltrate, which subsequently flows
into the renal tubules. Glomerular injury resulting in
disruption of glomerular filtration rate (GFR) is one
of the major causes of intrinsic AKI.
●Renal tubule – Reabsorption and secretion of
solute and/or water from the ultrafiltrate occurs
within the tubules. Acute tubular necrosis due
to nephrotoxins or hypoperfusion is one of the
major causes of intrinsic AKI.
●Urinary tract – The final tubular fluid, the
urine, leaves the kidney, draining sequentially
into the renal pelvis, ureter, and bladder, from
which it is excreted through the urethra.
Postrenal AKI is due to obstruction of urine
anywhere along the urinary tract in a single
kidney, and in patients with two kidneys,
bilateral obstruction usually at the bladder or
urethral level
Prerenal disease
is caused by reduced renal perfusion. It is the most
common form of AKI and is due to hypovolemia
(bleeding or gastrointestinal, urinary or cutaneous
losses), or reduction of effective circulation (eg,
heart failure, septic shock, and cirrhosis). (GFR) is
reduced, renal tubular function remains intact with
avid reabsorption of sodium and water in response
to renal hypoperfusion, leading to oliguria. When
normal renal perfusion is restored, urine flow and
GFR usually return to normal.
●Intrinsic renal disease – Intrinsic or intrarenal
AKI is characterized by structural damage to the
renal parenchyma. The most common causes of
intrinsic disease are prolonged hypoperfusion,
sepsis, nephrotoxins, or severe glomerular diseases.
●Postrenal disease – Postrenal or obstructive
AKI is typically the result of congenital or acquired
anatomic obstructions to the lower urinary tract
Intrinsic AKI — The most common
underlying
etiology is prolonged renal hypoperfusion
Vascular disease — include thrombosis (arterial
and venous), hemolytic uremic syndrome, and
vasculitides
Glomerular disease — The principal cause of
AKI is acute glomerulonephritis
Tubular and interstitial disease — Prolonged
prerenal AKI with reduction in renal perfusion, and
tubular nephrotoxins are important causes of
intrinsic AKI
Common exogenous nephrotoxins include
aminoglycosides, amphotericin B, contrast
agents, calcineurin inhibitors, and cisplatin
Intrinsic AKI can also be induced by the
release of endogenous nephrotoxins such as
myoglobinuria due to rhabdomyolysis and
hemoglobinuria due to intravascular hemolysis
Postrenal AKI — Postrenal AKI is due to
bilateral urinary tract obstruction or obstruction
of the urinary tract of a solitary kidney. Causes
of postrenal AKI include renal calculi, clots,
neurogenic bladder, and medications that cause
urinary retention
Clinical presentation
In most children, AKI presents with signs and
symptoms that result directly from alterations of
renal function.
* edema (due to progressive fluid
accumulation),
*decreased or no urine output,
*gross and microscopic hematuria, and/or
hypertension
HISTORY
●A short duration of vomiting, diarrhea, or
decreased oral intake associated with decreased
urine output suggests prerenal AKI.
●A history of bloody diarrhea 3 to 7 days prior
to the onset of oliguria suggests hemolytic
uremic S.
●A history of pharyngitis or impetigo a few
weeks prior to the onset of gross hematuria or
edema suggests PSGN
●In hospitalized patients, nephrotoxic
medications or periods of hypotension are
associated with intrinsic AKI.
●Other systemic complaints (eg, fever, joint
complaints, and rash) may be seen in patients
with autoimmune diseases or vasculitides, such
as Henoch-Schönlein purpura (IgA vasculitis).
Physical examination
The physical examination should include
measurement of blood pressure
assessment for edema and recent weight gain,
signs of systemic disease, such as rash or joint
disease
Laboratory and imaging evaluation
Laboratory tests and renal imaging that may be
useful in determining the underlying etiology of AKI
include:
●Urinalysis
●Fractional sodium excretion to differentiate
between pre- and intrinsic AKI
●Renal ultrasound
URINALYSIS
●Muddy brown granular casts and epithelial cell
casts are highly suggestive of intrinsic AKI or
acute tubular necrosis (ATN
● red cell casts is diagnostic of GN .
The concurrent finding of dysmorphic red cells
and heavy proteinuria indicates an active
“nephritic” urinary sediment, which is also
commonly associated with glomerulonephritis
●Pyuria with white cell, granular, or waxy casts are suggestive
of tubular or interstitial disease, or urinary tract infection .
White cells and white cell casts may also be seen in acute
glomerulonephritis.
●A positive response for heme on a urine dipstick in the
absence of red blood cells in the sediment is seen in patients
with hemolysis or rhabdomyolysis.
●The urinalysis in children with prerenal AKI is typically
normal
●Urine specific gravity – Loss of concentrating ability is an
early and almost universal finding in ATN with a urine
specific gravity below 1.010. In contrast, urine specific
gravity greater than 1.020 is suggestive of prerenal
disease.
Urine osmolality is a more accurate measure of
concentrating ability. Patients with ATN generally have
urine osmolality below 350 mosmol/kg, whereas patients
with prerenal disease usually have values above 500
mosmol/kg
Fractional excretion of sodium — The fractional excretion
of sodium (FENa) is the most commonly used laboratory
test to differentiate between prerenal AKI and intrinsic
disease due to ATN.
FENa is calculated from measured concentrations of
urinary sodium (UNa) and creatinine (UCr), and plasma
sodium (PNa) and creatinine (PCr):
UNa x SCr
FENa, percent =
——————— x 100
SNa x UCr
●A FENa below 1 percent suggests prerenal AKI, in
which the reabsorption of almost all the filtered
sodium represents an appropriate response to
decreased perfusion
●A FENa above 2 percent suggests ATN
●A FENa between 1 and 2 percent is nondiagnostic
Serum creatinine — The most common laboratory
test used to identify reduced glomerular filtration
rate (GFR) as an indication of AKI is serum
creatinine
●Newborn – 0.3 to 1 mg/dL (27 to 88 micromol/L)
●Infant – 0.2 to 0.4 mg/dL (18 to 35 micromol/L)
●Child – 0.3 to 0.7 mg/dL (27 to 62 micromol/L)
●Adolescent – 0.5 to 1 mg/dL (44 to 88 micromol/L
●Complete blood count – Microangiopathic
hemolytic anemia associated with
thrombocytopenia in HUS
Eosinophilia and/or urine eosinophiluria may be
present in some cases of interstitial nephritis
●Complement studies including C3, C4, CH50, and
AH50 – Hypocomplementemia is seen in patients
with poststreptococcal glomerulonephritis (PSGN),
shunt nephritis, and nephritis associated with
subacute bacterial endocarditis
●Serologic testing for streptococcal infection –
●Elevated serum levels of aminoglycosides are
associated with ATN
●Uric acid – AKI may result from markedly elevated
uric acid levels, which may occur in children with
tumor lysis syndrome secondary to chemotherapy
treatment of childhood leukemia or lymphoma
Renal imaging — A renal ultrasound should be
considered in all children with AKI of unclear
etiology
Renal biopsy — A renal biopsy is rarely indicated
in AKI
The most common differential diagnosis for
acute kidney injury (AKI) is the initial
presentation of chronic kidney disease (CKD).
MANAGEMENT
●Fluid management
●Electrolyte management
●Nutritional support
●Adjustment of drug dosing
●Renal replacement therapy
●Specific pharmacologic therapies
PROGNOSIS AND OUTCOME
AKI is associated with increased mortality and longterm morbidity.
Mortality — In the United States, reported in- •
hospital mortality rate of children with AKI is
about 15 percent The mortality rate is lower
among children who develop non-intensive care
unit (ICU) setting, with reports ranging from 1.5
to 9.5 percent .
in the ICU setting about 30 percent