ACUTE RENAL
FAILURE
Academic Half Day
February 9, 2012
Objectives
To review:
 the etiologies of acute kidney injury (AKI) in the
pediatric population
 the work-up/diagnosis of AKI
 the management of AKI
 What is AKIs?
“abrupt reduction in kidney function as measured
by a rapid decline in GFR”

Previously known as Acute Renal Failure

Now failure represents one end of the spectrum
Classification - pRIFLE
U/O
Risk
eCCl dec 25%
Injury
eCCl dec 50%
Failure
eCCl dec 75%/ <0.3cc/kg/h x 24h/
< 35ml/min/1.73m2 Anuric x 12h
Loss
End-stage
<0.5cc/kg/h x 8h
U/O
<0.5cc/kg/h x 16h
Persistent failure >4wks
Failure > 3 months
Leads to:
 Impaired excretion of nitrogenous waste
 Impaired water and electrolyte balancing
 Impaired acid/base regulation
 Impaired vascular tone regulation
Burden of disease
Incidence (US): 0.8/100 000; ~1/10 in ICU
 Increasing
Independent risk factor for ICU mortality
Increases length of hospital stay
May lead to chronic renal failure (40-50% ICU)
Etiologies: a general approach
Though likely multifactorial, can be divided into:
Pre-renal
Renal
Post-renal
Pre-renal causes:
Any cause which results from kidney
seeing to little blood flow
Volume deplete:
 GI
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Bleeding
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Trauma
Surgery
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Vomiting
Diarrhea
Kidney sees less volume:
 Sepsis
 CHF
 Cirrhosis
 Vascular - also consider in renal
Diuresis

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Diabetes - DM, DI
Drugs

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RAS
Thrombus
Takayasu, PAN, KD
Drugs


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NSAIDs
ACEi
ARBs
Renal causes
Vascular:
Glomerular:
Microvasculature:
Glomerulonephritis: Acute tubular necrosis
•Post-infectious
-secondary to nephrotoxic
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Sickle cell disease
HUS
Tumour lysis
rhabdomyolysis
?Syndromes


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Hepatorenal
Cardiorenal
Pulmonary-renal
?Sepsis
inflamm, not all volume
related
•membranoproliferative
•SLE
•HSP
Tubulo/Interstitial:
insults or poor perfusion
Acute interstitial nephritis
-drugs
-infxn
Cortical dysplasia
-hypoxia/ischemia->infarct
-toxins/severe HUS
Hemolytic Uremic
Syndrome
History of Ecoli, Shigella, shiga-toxin…
Atypical (non-diarrhea, non-shiga-toxin)
Hemolytic anemia with fragmented RBCs
Thrombocytopenia
Renal injury
CNS, liver, pancreas can also be affected
Post-infectious
glomerulonephritis
Occurs in ages 5-12, post-GAS.
Presentation can be asymptomatic to nephritis
complete with gross hematuria, proteinuria,
HTN, edema
Labs: abnormal urinalysis, low complement
Rx: supportive.
Prognosis: most make complete recovery.
HSP
-Causes renal issues d/t IgA deposition.
-A/W palpable purpura, arthritis, abdo pain.
-Renal more likely to be an issue in older kids
-Rx: if crescenteric, GN - steroids.
-prognosis: often relapses. Can have late
deterioration even if full recovery. 10-30%
adults go on to have end-stage disease.
Acute Tubular
Necrosis
Describes an end effect of tubular damage…
 Secondary to perfusion insults
 Secondary to toxins
Change in blood flow, obstruction and passive
filtrate backflow into tubular cells can cause a
cycle leading to further death…
AIN
Drugs (71%) - 1/3 antibiotics

Penicillins, cephalosporins, NSAIDs, sulfonamides, cipro,
rifampin, PPIs, allopurinol… and more
Infection (15%)

Strep, Legionella, leptospirosis, CMV, EBV… many
Tubulointersitial nephritis and uveitis (5%)
Autoimmune: SLE, Sjogren’s
Sarcoidosis
Idiopathic (8%)
Nephrotoxins
Vascular effect

ACEi, cyclosporine, tacrolimus
Tubular effect



AIN
Proximal: aminoglycosides, amphotericin B,
cisplatin, immunoglobulins, contrast
Distal: NSAIDs, ACEi, lithium, cyclophosphamide
Obstruction: sulfa, acylovir, methotrexate
Post-renal causes
Two kidneys - distal or bilateral proximal obstruction
Single kidney - obstruction anywhere
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Posterior urethral valves
Ureteropelvic junction obstruction
Ureterovesicular junction obstruction
Ureterocele
Stones
Tumour
Hemorrhagic cystitis
Neurogenic bladder
On history…
? pre-renal:


Vomiting, diarrhea, bleeding, sepsis, dec PO
Drug use - inc NSAIDs
? renal:


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Bloody diarrhea? (HUS) Recent illness? (PSGN) Crush
injury?
Drug use: aminoglycosides, antifungals, chemo
Associated lung/heart/liver symptoms? (dual organ)
? post-renal:
On physical…
Pre-renal:

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Dehydration
Signs of heart failure/cirrhosis/sepsis
Renal:

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Edema (nephrotic syndrome)
Purpura (HSP
Post-renal: palpable bladder?
What to order?
BUN, Cr, lytes, fractional excretion of sodium
Urinalysis
On labs…
Everyone gets a urinalysis…
NORMAL:
-pre-renal
(may be concentrated)
-post-renal
-ATN
ABNORMAL:
-brown granular/epithelial
casts = ATN
-red cell casts =
glomerulonephritis
-proteinuria = glomerular
-pyuria, white cell casts = UTI
or glomerulonephritis (postinfxn)
-hematuria = AIN, vasculitis,
infarction, obstruction
And even more information
from urine…
Urine osmolality:


Typically low in ATN (<350 mosmol/kg)
Typically high in pre-renal disease (>500)
Urine volume:
Often low, especially given criteria for AKI.
However, some ATN is non-oliguric
Urine eosinophils
Urine sodium…
Sodium excretion
Why? Helps distinguish pre-renal vs ATN…


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>30-40 mEq/L = ATN
<10 mEq/L = effective volume depletion
(20-30 in infants)
BUT what if there is a large urine output?
Fractional Excretion of Sodium
FENa compensates for the urine output…
UNa x PCr
PNa x UCr
…can also be thought of as
UNa/PNa
UCr/PCr
<1% --> pre-renal disease
1-2% --> ??
>2% --> ATN
Bloodwork…
CBC: look for MAHA, thrombocytopenia
Extended lytes. Renal injury can result in:

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Hyperkalemia
Hyperphosphatemia
Hypocalcemia
Metabolic acidosis
Other options, depending on history: ANCA,
ANA, ASOT, complement, drug levels…
And of course, creatinine
Creatinine is usually elevated

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Normal Cr varies by age
Age
Normal range (umol/L)
Newborn
27-88
Infant
18-35
Child
27-62
Adolescent
44-88
Note Cr can NOT be used to estimate GFR in
acute kidney injury…
This is why the search is on for a “troponin of the
kidneys”
Troponin of the kidneys?
Unfortunately, not yet… Some ideas:

Urinary neutrophil gelatinase-associated lipocalin
(NGAL)

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Increased 50-fold, and 24h before serum Cr
Has been shown to predict AKI severity in SLE, HUS, renal
transplant patients
Kidney injury molecule - 1 (KIM-1)
IL-18
Imaging
Ultrasound - in all children if etiology unclear
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# of kidneys
Size of kidneys
Obvious parenchymal damage
Obstruction
Thrombus/vessel occlusion
Renal biopsy
Only when diagnosis remains unknown, or
there is a failure to respond to treatment
Approach summary:
pRIFLE met
-estimated CrCl
-oliguria
NORMAL
urinalysis
ABNORMAL
urinalysis
Ultrasound
PRE-RENAL
Low ECF volume
-GI loss
-diuresis
-hemorrhage
RENAL
POST-RENAL
Low vol to kidney
-bilateral ureteric obstruction
-heart failure
-single kidney + ureter obs
-m eds (NSAIDs, ACEi, ARB)
-bladder/urethra obs
-vascular disease
Vascular disorders
Artery
-RAS
-Takayasu, PAN, KD
-can think of drugs here too
Veins
-thrombosis
Parenchymal disorders
Glomerular disorders
Tubular disorders
AIN
-drugs
-infection
-autoimmune
ATN
-ischemia
-contrast
plugged
-crystals
-globins
-drugs
Treatment
Principles:
1. FEN
2. Avoid complications
3. Treat underlying cause
Generally pediatric nephrology will be involved.
FEN - fluids
Child can be hypo-, eu- or hypervolemic.
FLUID STATUS
Hypovolemia
Goal:
maintain renal perfusion
Euvolemia
Hypervolemia
Type Title Here
Crystalloids (NS)
-bolus, rpt
-no change?
Consider invasive monitors
Monitor ins/outs
-daily weights
-ins=outs + insensibles
Fluid removal/restriction
-furosemide (2-5mg/kg)
-no change?
Consider RRT
HTN can occur and is usually secondary to volume overload.
Treatment based on diuretic response, severity.
FEN - electrolytes
Hyperkalemia - if severe (>7) - C BIG K Die…
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Don’t give K (IVs, low K diet)
stabilize the cardiac membrane - IV calcium
gluconate
Move K ECF -> ICF by:
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Insulin (with glucose)
Sodium bicarb
Beta agonists
Remove K from the body - kayexalate
Can try diuretics - unlikely to do enough
RRT if the above doesn’t work
FEN - electrolytes
Acidosis

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Respiratory compensation can be enough
Sodium bicarb ONLY if life-threatening and/or
contributing to hyperkalemia
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Def not if pH >7.2 or bicarb >14mEq/L
Can decrease Ca further -> seizures
Can increase intravascular volume
If refractory volume overload, hypernatremia ->
RRT
FEN - electrolytes
Hyperphosphatemia:

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Low phosphate diet
Binders
Hypocalcemia:

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Calcium gluconate
Can pre-empt if sodium bicarb being given
FEN - Nutrition
AKI is a catabolic state
Ensure adequate calories
- 120kcal/kg/d in infants
- usual maintenance for children
PO -> enteral -> TPN
If fluid balance off with adequate nutrition: RRT
Avoid complications
Including making things worse…so no:
Aminoglycosides
NSAIDs
Antifungals
Immunosuppressive drugs
Contrast media
Renal Replacement Therapy
(RRT)
Indications:
1. Uremia s/s - pericarditis, neuropathy,
decline
2. Azotemia - BUN >36
3. Refractory fluid overload - HTN, pulm
edema, CHF
4. Refractory hyperK, hypo/hyperNa, acidosis
5. Nutritional support with fluid balance issues
RRT
Options:
Continuous renal replacement therapy
Peritoneal dialysis
Hemodialysis
Prognosis
Mortality: 60% (critically ill)
20-25% go on to have some degree of
chronic renal issues
Take home points
Etiology:
Best divided into pre-, renal and post-renal
Work-up:
Urinalysis, ultrasound, bloodwork…
Treatment:
Fluids - close balance
Electrolytes - esp K, PO4, Ca
Acidosis
Nutrition
Dialysis - talk later today
References
Akcan-Arikan A, Zappitelli M, Loftis L, Washburn K, Jerrerson L, and Goldstein S. Modified RIFLE
criteria in critically ill children with acute kidney injury. Kidney International; 2007: 71: 1028-35.
Basu R, Devarajan P, Wong H, and Wheeler S. An update and review of acute kidney injury in
pediatrics. Pediatric Critical Care Medicine; 2011: 12(3): 339-47.
Imam A. Clinical presentation, evaluation, and diagnosis of acute kidney injury (acute renal failure)
in children. Uptodate. Accessed Feb 8, 2012 at
http://www.uptodate.com.ezproxy.lib.ucalgary.ca/contents/clinical-presentation-evaluation-anddiagnosis-of-acute-kidney-injury-acute-renal-failure-inchildren?source=search_result&search=acute+kidney+injury&selectedTitle=2~150
Imam A. Prevention and management of acute kidney injury (acute renal failure) in children.
Uptodate. Accessed Feb 8, 2012 at
http://www.uptodate.com.ezproxy.lib.ucalgary.ca/contents/prevention-and-management-of-acutekidney-injury-acute-renal-failure-inchildren?source=search_result&search=acute+kidney+injury&selectedTitle=1~150
Kliegman R, Stanton B, Geme J, Schor N, and Behrman R. Nelson Textbook of Pediatrics 19th e.
Elsevier; 2011: 1814-22.