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Infant Acute Kidney Injury
Maricor Grio, MD, MS
Orlando Health
Arnold Palmer Hospital for Children
Orlando, Florida
[email protected]
Infant AKI
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How common is this problem?
What are the causes?
Who are the patients at risk?
What are the prevention and treatment options?
What are the long term consequences?
Definition of AKI
 Reduction of GFR to a level insufficient to adequately filter and
excrete solute and water and maintain fluid and electrolyte
balance
 Urine volume below 0.5-1ml/kg/hr after 1st day
 Urine volume is a poor indicator of renal function
 Increased serum creatinine > 1.5mg/dl
 Serum creatinine is a poor indicator of renal function
 Daily rise in serum creatinine of 0.3mg/dL to 0.5 mg/dL?
Creatinine Clearance According
to Gestational Age
CCr (ml/min/1.73M2
35
30
25
20
15
10
5
0
28wks
32wks
36wks
40wks
Gestational age (wks)
Chevalier.J Urol.1996:156
Serum Creatinine During First Three
Months in LBW Infants < 2000g
1.5
Creatinine (mg/dl)
1.3
1.1
0.9
0.7
0.5
0.3
0.1
-0.1
10
20
30
40
50
60
70
80
90
Age (days)
Stonestreet. Pediatr.1978:61:788-789
Incidence and Epidemiology of AKI
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Precise incidence and prevalence is unknown
Incidence of AKI in NICU patients is 6-24%
60% non-oliguric / 25% oliguric / 15% anuric
Higher incidence in patients undergoing cardiac
surgery
 More common in neonates with severe asphyxia
 Some infants may have genetic risk factors for
development of AKI
Andreoli. Seminars in Perinat.2004:28 (2):112-123
Pediatric AKI Epidemiology at a Tertiary
Care Center 1999-2001 (n=254 pts)
0-30 days
1-12 mos
1-5 yrs
6-15 yrs
16-21 yrs
Hui-Stickle et al. AJKD.2005: 45:96
AKI in Neonates 1999-2001 n=62 pts
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Ischemic ATN most common in 16 pts (26%)
Estimated GFR 11.5 + 89.8 ml/1.73m2
56% survived
Length of ICU stay 97 days
58% required renal replacement therapy
Hui-Stickle et al. AJKD.2000545:96
Infant AKI

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


How common is this problem?
What are the causes?
Who are the patients at risk?
What are the prevention and treatment options?
What are the long term consequences?
Etiology of AKI
Pre-renal AKI
Intrinsic AKI
Obstructive AKI
Prenatal AKI
Etiology of Prenatal AKI
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Obstructive uropathy
Renal hypoplasia/dysplasia
Renal cystic disease
Agenesis
Nephrotoxic agents
Intrauterine infection
Intrauterine medications- NSAIDs, ACE-i
Complications during pregnancy and delivery
Etiology of Pre-renal AKI
 Hypovolemia
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Dehydration
Gastrointestinal losses
Hemorrhage
Salt wasting (renal or
adrenal)
 Central or nephrogenic
diabetes insipidus
 Third space losses
(sepsis, traumatized
tissue)
 Cardiac Failure
 Congenital heart
disease
 Congestive heart
failure
 Pericarditis
 Cardiac tamponade
Etiology of Pre-renal AKI
 Hypotension
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Sepsis
DIC
Bleeding
hypothermia
 Hypoxemia
 Neonatal asphyxia
 Severe hyaline
membrane disease
 Pneumonia
 Cardiac surgery
Etiology of Acquired Intrinsic AKI

Acute Tubular Necrosis
 Ischemic / hypoxic insults
 Drug induced
 Aminoglycosides
 NSAIDS
 Antifungal agents
 Antiviral agents
 Chemotherapy
 Intravascular contrast
 Toxin mediated
 Uric acid nephropathy
 Hemoglobinuria
 Myoglobinuria
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Interstitial Nephritis
 Infectious
 Drug induced
 Idiopathic
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Vascular Lesions
 Cortical necrosis
 Renal artery thrombosis
 Renal vein thrombosis
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Infectious Causes
 Sepsis
 Pyelonephritis
Etiology of Congenital Intrinsic AKI
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Bilateral renal agenesis
Dysplasia/ Hypoplasia
Cystic renal diseases
Congenital nephrotic syndrome
Congenital nephritis
Etiology of Obstructive AKI
 Congenital obstructive uropathy
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Obstruction in a solitary kidney
Bilateral UPJO
Bilateral UVJO
Large obstructive ureterocele
Posterior urethral valves
Urethral stenosis/atresia
Neurogenic bladder
 Acquired obstruction
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Foley catheter obstruction
Fungus balls
Urethral trauma
External compression
Posterior urethral valves
Hydronephrosis
Cystic Renal Disease
Infant AKI
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How common is this problem?
What are the causes?
Who are the patients at risk?
What can we do to prevent this problem?
What are the prevention and treatment options?
What are the long term consequences?
Patients at Risk
Prematurity
LBW infants
IDM
CHD
Perinatal asphyxia
Sepsis
RDS
Ventilators
Vasopressors
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Volume depletion
Hemorrhage
Aminoglycosides
NSAIDS
Antifungal
Chemotherapy
Hemolysis
Postoperative (cardiac)
Contrast Agents
AKI in Asphyxiated Term Neonates
Points
0
1
2
3
Fetal
HR
Nl
Variable
Decel.
Late
Decel.
Prolonge
d
Brady
Apgar
(5min)
>6
5-6
3-4
0-2
Base
Deficit
<10 10-14
15-19
>19
Scores 6-9
Inc. LFT
Death
Sz
ARF
Scores 1-5
0
20
40
% of pts
60
80
100
Karlowics. Ped.
Nephrol.1995
TNF-, IL-1B, IL-6 & IL-10 haplotype variants
in VLBW infants with AKI & non-AKI
60
%
50
*p<0.05
*
40
30
20
10
0
AKI
TNF-308/IL-1B
IL-1/IL-6
TNF-308/IL-6
IL-10/IL-6
non-AKI
TNF-308/IL-10
Vasarheli et al. Pediatr Nephrol .2002:17:713
Variance of ACE and AT1 receptor gene in
VLBW infants with AKI and non-AKI
40
35
%30
25
20
15
10
5
0
AKI
ACE-II
ACE-ID
non-AKI
ACE-DD
ATr-AA
Atr-AC
Atr-CC
Vasarheli et al. Pediatr Nephrol .200116:1063
Diagnostic Evaluation in AKI
 Prenatal history
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Family history
Medications
Oligohydramnios
Complications during pregnancy
Prenatal ultrasounds
 Delivery
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Fetal distress
Bleeding
Infections
Medications
Clinical Evaluation of AKI
 Chart review
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Intake and output
Infections
Respiratory distress
Medications
Contrast studies
Surgical procedures
 Physical examination
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General appearance (Potter’s sequence)
Hydration status
Cardiac examination
Pulmonary examination
Abdominal masses
Diagnostic Evaluation in AKI
 Laboratory studies
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Urinalysis and culture
Urine electrolytes / creatinine / osmolality
Urine protein / creatinine
Electrolytes BUN and creatinine / osmolality
Calcium / phosphorus and uric acid
 Imaging studies
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Renal ultrasound with doppler
VCUG
CT
Renal scan (DTPA or MAG3)
Echocardiogram
CXR
Diagnostic studies in AKI
Prerenal
ATN
BUN/Cr
>20:1
<20:1
Urine Na
< 20 mEq/L
30-40mEq/L
U. Osmo
> 350
< 300
FeNa
< 2.5%
2.5-3%
U/P Osmo
> 1.3
< 1.3
UA
Increased specific Prot / Heme
gravity . Minor
Granular &
changes or NL
epithelial casts
Infant AKI
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
How common is this problem?
What are the causes?
Who are the patients at risk?
What are the prevention and treatment options?
What are the long term consequences?
Treatment of AKI
Conservative
Medical Therapy
Renal Replacement
Therapy
Renal Transplantation
Conservative treatment in AKI
 Avoiding other nephrotoxic insults
• Antibiotics
• Antifungal
• NSAIDS
• Contrast agents
• Surgical procedures
 Fluid allowance
• Insensible losses
• Ongoing losses
Insensible Water Loss During the First Week of Life
100
(ml/kg/24hr)
80
60
40
20
0
750-1000
1001-1250
1251-1500
>1501
Birth weight (g)
Clolherty. Manual of Neonatal Care.1998
Factors Affecting Insensible Water Losses
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Prematurity: 100-300%
Radiant Warmer: 50-100%
Phototherapy: 25-50%
Hyperventilation: 20-30%
In. activity: 5-25%
Hyperthermia: 120C
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Incubator: 25-50%
Humidified air: 15-30%
Sedation: 5-25%
Dec. activity: 5-25%
Hypothermia: 5-15%
Protein Requirements in Newborns with AKI
Protein g/kg/d
4
3
PD
2
HD
1
CRI
0
0-6 month
6-12 month
CRI
HD
PD
Yiu VW et al. J Renal Nutr .1996.6:203
Energy, Calcium and Phosphorus Requirements in
Newborns with AKI
500
400
300
200
100
0
0-2 moth
Ca (mg/d)
2-6 month
P04 (mg/d)
Kcal/Kg/d
Yiu VW et al. J Renal Nutr.1996 6:203
Conservative Management of AKI
 Adjustments of medications according to renal function
 Prevention and management of complications
• Fluid overload with HTN and RDS
• Electrolyte imbalance
 Sodium
 Potassium
 Uric acid
• Metabolic acidosis
• Anemia
• Bone and mineral metabolism disorders
 Hypocalcemia
 Hyperphosphatemia
Treatment of AKI
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Dopamine
Diuretics
Phosphorus binders
Non-dialytic treatment for hyperkalemia
 NaHC03: 1-2meq/kg IV over 10-30 min
 Glucose / Insulin: (0.5g/kg) /( 0.1U/kg) IV over 30 min
 Calcium gluconate (10%): 0.5-1cc/kg IV over 5-15 min
 B-Agonist (albuterol): 5-10mg nebulizer in adults 2.5mg in
children?
 Kayexalate (0.5-1g/kg) PO or PR Q6h
Future Therapy to Decrease Injury and
Promote Recovery?
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IGF-1
ANP
Epidermal growth factor
Hepatocyte growth factor
Melatonin stimulating factor
Thyroxine
C5a receptor antagonist
Selective inhibitors of inducible nitric oxide synthase
Inhibition of monocyte chemoattractant protein-1
Theophylline Prophylaxis in Perinatal Asphyxia
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Randomized, placebo controlled study
Single theophylline dose vs. placebo (n=70)
Theophylline group (n=40) ; placebo group( n=30)
Higher GFR and lower beta 2 microglobulin excretion
in theophylline group
 Single dose theophylline (8mg/kg) in the 1st hour of
birth may prevent AKI in asphyxiated term infants
Bhat et al..J Pediatr.2006:149:180-184
Indications for Renal Replacement Therapy (RRT)
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Oliguria with fluid overload
 Respiratory distress
 Hypertension
 CHF
Electrolyte imbalance
 Hyperkalemia
 Hyponatremia
 Hyperphosphatemia
 Hypocalcemia
 Hyperuricemia
Uremic symptoms
Nutritional needs
Others (blood products, medications, other fluids)
Options for RRT
 Peritoneal dialysis
 Manual PD
 Cycler PD
 Hemodialysis
 Continuous renal replacement therapy
 CAVH
 CAVHD
 CVVH
 CVVHD
Renal Replacement Modality
40
30
% of
patients 20
10
0
Hemodialysis
Peritoneal dialysis
CRRT
Beisha et al. Pediatr. Nephrol.1995
Peritoneal Dialysis
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Access less of a problem
No special equipment needed
Can be done by NICU nurses
Can be done in pts of all size
Less need for blood products
No need for anticoagulation
Gradual change in volume
and electrolyte composition
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Relatively few if any
contraindications
 Recent abdominal surgery
 Ostomies
 V-P shunt?
 Peritonitis?
 Peritoneal scarring
 Abnormal anatomy
Modality of choice for infants
with ESRD
Hemodialysis in Infants Less Than 5Kg
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216 acute hemodialysis treatments 1980-1991
33 pts (32-43wks) with wt of 2.2-4kg / total of 216 treatments
Age 2-120 days (median 10 days)
Indications for hemodialysis
 Hyperammonemia (8pts)
 Intrinsic or primary renal disease (7pts)
 Acute kidney injury (18pts)
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Hemodialysis Access
 7 Fr double lumen catheter (49%)
 ECMO circuit (24%)
 Umbilical vessels (27%)
Jabs et al. KI.Vol45.1994.903-906
Hemodialysis in Infants Less Than 5Kg
100
• 9 Rx discontinued prematurely
• Hypotension
• Technical problems
• Mortality not influenced
• Weight
• # of HD treatments
% survival
80
60
40
20
0
AKI
Hyperammonemia
Renal
Jabs et al. KI.Vol45.1994.903-906
Who are the non-candidates for RRT?
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Severe neurological injury
Inoperable life threatening congenital heart disease
Severe lung disease
Severe congenital anomalies
Extreme prematurity?
Anticipated mortality?
Parents wishes need to be considered
The decision needs to be individualized
Close communication with parents is important
Factors Influential in Deciding to initiate ESRD in
Infants 217 Pediatric Nephrologist Around the World
Family socioeconomic status
1.8 + 1.7
1.7 + 1.7
Hospital / Government budget
0.5 +1.1
0.5 + 0.9
Family’s right to decide
3.7 + 1.3
4.0 + 1.2
Doctor’s right to decide
2.9 + 1.3
3.0 + 1.3
Coexistent serious medical abnormalities 4.8 + 0.6
4.8 + 0.5
Anticipated morbidity for child
4.1 + 1.2
4.3 + 1.0
Presence of oliguria
1.8 + 1.8
1.9 + 1.9
No influence = 0
Strong influence = 5
Responses 1-12 mo (x + SD)
Geary et al. J Pediatr.1998:133:154
If parents reject RRT for otherwise normal infants with ESRD, is
this USUALLY or EVER ethically acceptable to you ?
Usually acceptable
< 1mo
1-12mo
Ever acceptable
< 1mo
1-12mo
Canada
6/11
2/16
11/12
11/16
France
4/7
3/10
5/7
8/11
Germany
13/19
11/25
19/19
18/25
Holland
1/3
0/3
3/3
3/3
Italy
0/5
0/7
2/6
0/7
Japan
3/11
2/13
3/11
3/13
UK
19/26
5/26
25/26
20/25
USA
38/88
24/93
71/89
59/98
Unidentified
3/4
0/6
3/3
4/6
Total
87/174
49/199
142/176
126/204
Geary et al. J Pediatr.1998. 133:154
Infant AKI
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
How common is this problem?
What are the causes?
Who are the patients at risk?
What are the prevention and treatment options?
What are the long term consequences?
Outcome and Prognosis
 Highly dependent on the etiology of AKI
 Factors associated with poor prognosis
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Multiorgan system failure
Hypotension / hemodynamic instability
Need for pressors
RDS with need for mechanical ventilation
Oligoanuria and need for dialysis
 Overall mortality 10-61%
 Nephron loss can lead to long-term complications
 Proteinuria
 Hypertension
 Chronic renal insufficiency
36 Month Post Transplant Patient Survival
100
80
60
40
20
0
CRT
0-1yr
2-5yr
LRD
6-12yr
>12yr
NAPRTCS 2004
Neurodevelopmental Outcome of Children
Initiating PD During Early Infancy
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34 infants initiated long-term PD
< 3mo of age
28/34 pts survived >1 year of
life and underwent a formal
neurodevelopment evaluation
27/28 pts received
supplemental nasogastric tube
feedings
Calcium carbonate was used as
the only P04 binder
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At 1yr HC SDS 0.96 + 1.2
At 1yr, developmental score in
22 pts (79%) were within avg
range and in 1 pt (4%)
significantly delayed
19 pts retested at > 4yrs, 15 pts
(79%) performed in the average
range and 1pt (5%) in the
impaired
15/16pts (94%) > 5yrs of age
attended regular school in age
appropriate classrooms
Warady et al. Pediatr.Nephrol. 1999:13(9)759
Summary
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AKI is a relatively common among sick infants
 Certain infants are at higher risk
Probably under diagnosed in NICU nurseries
 Non-oliguric presentation is most common
 The diagnosis should follow a stepwise approach
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 History
 Physical examination
 Diagnostic evaluations
Clinical knowledge and technological advancements have allowed
for a variety of therapeutic options
Long-term renal follow up is necessary
Management of AKI in infants is challenging but reasonable longterm outcome is now possible
More data is needed