8th International Conference On
Paediatric Continuous Renal Replacement
Therapy (pCRRT)
16th - 18th July 2015
Queen Elizabeth II Conference Centre, London, UK
Acute Kidney Injury in Neonates
Jordan M. Symons, MD
University of Washington School of Medicine
Seattle Children’s Hospital
Seattle, WA - USA
AKI: Definition and Diagnosis
• Abrupt reduction in GFR
• Differential diagnosis includes:
– Pre-renal
• Volume depletion; cardiac dysfunction
– Renal
• Vascular; glomerular; tubular; interstitial
– Post-renal
• Obstruction
• Complex, multi-factorial physiology
Neonatal AKI: Special Challenges
• Specific stresses unique to the neonate
– Different renal physiology in newborn
• Risks associated with neonatal illness
and its treatment
– Low birth weight; fluid loss; infection; drugs
• Our ignorance of details in neonatal AKI
– Do we really know which babies have AKI?
Neonatal Physiology with
Implications for the Kidney
GFR is Low in
the Newborn
• Transition to postnatal status favors
flow to lungs
• High renal
resistance at birth
• Even lower GFR
in preterm infant
Delayed Renal Stabilization in Preterms
Not in steady state
Tubular Function is Immature
in the Newborn
Na+
• Immature isoforms of
multiple channels
• Reduced function of Na/K
ATPase
• Lower tubular surface area
• Diuresis is normal and
expected after birth
• Risk for more tubular
dysfunction with stress
Greater
Sodium
Losses
Na+
Neonatal Water Balance is Different
•
•
•
•
Immature tubule
Diminished aquaporin function
Normal excretion ability
Lower capacity to retain free water
– Concentrating capacity improves with
development
• Risk for greater water loss with illness,
prematurity
Transepidermal Water Loss
• Preterm insensible loss is higher
– Skin, respiratory tract
– 15x higher in preterm compared to term
• Highest immediately after birth
• Clinical maneuvers to limit water loss
– Closed incubator
– Humidification
– Skin care
Water Loss by Gestational Age and
Chronological Age
Hartnoll, Sem Neonatol, 2003(8): 307-13
Neonatal Renal Risks from
Clinical Conditions
Risk Factors for Neonatal AKI
•
•
•
•
•
Very low birthweight
Congenital Heart Dz
Cardiac bypass
ECMO
The depressed or
asphyxiated infant
• Renal anomalies
(CAKUT)
• Hypotension or
hypoperfusion
• Infection/sepsis
• Drugs
• Umbilical
catheterization
• Multi-organ disease
Physiology
Illness
AKI
Prematurity
Interventions
Neonatal AKI Epidemiology:
What is the Scope of the Problem?
Neonatal AKI: Challenging to Define
• Often non-oliguric
• Unclear baseline
• Not steady state
Jetton & Askenazi, Clin Perinatol 2014
• Less frequent labs
• Suboptimal markers
• Documentation issues
Neonatal AKI Incidence:
Select Populations
Population
Findings
Very Low Birth Wt1
AKI: 41/229 (18%); hazard ratio (HR) for death = 9.3
(95% CI 5.1–21)
Congenital Heart Dz2
AKI: 225/430 (52%); odds ratio (OR) for death up
with higher AKI stage (stage 2 OR=5.1 (95% CI
1.7–15.2); stage 3 OR=9.5 (95% CI 2.9–30.7))
ECMO3
Higher AKI rate in non-survivors (19% vs 3.9%;
P<0.0001); OR for death = 3.2 (P<0.0001)
Perinatal depression4
Higher level of AKI for infants with severe asphyxia
(12/25) vs. moderate asphyxia (1/11)
1. Koralkar et al. Pediatr Res 2011
3. Askenazi et al. Pediatr Crit Care Med 2011
2. Blinder et al. J Thorac Cardiovasc Surg 2011
4. Kaur et al. Ann Trop Paediatr 2011;
Management of Established AKI:
Pharmacotherapy
Attempted Therapies
• Diuretics
• Mannitol
• Dopamine
• Fenoldopam
• Glucocorticoids
• Atrial natriuretic peptide
• N-acetylcysteine (other
than contrast-induced AKI
Definitive Therapies
• Hmmmm . . . . .
Prophylaxis of Neonatal AKI
• Theophylline may protect asphyxiated
infants against AKI:
• However:
– Insufficient information on long-term renal
or neurodevelopmental outcome
– Different doses between trials
– Toxicity remains unclear
– Unsure of interaction/benefit with
hypothermia
Al-Wassia et al. J Perinatol 2013
Conservative Management of
Established AKI: Traditional Approach
•
•
•
•
•
Limit fluid intake
Limit input of retained substances
Augment losses (diuretics)
Try not to mess up
Wait and Hope
Renal Replacement Therapy
for Neonatal AKI
Askenazi et al. J Ped 2013
Acute Kidney Injury in
Neonates: Summary
• Neonates are at special risk for AKI
– Unique physiology
– Clinical risks
– Nature of our interventions
• Like older children and adults, AKI is a
significant problem for the newborn
– Morbidity and mortality
• Management remains a challenge
– Meeting the challenge is why we are here!
Thank You for Your Attention
and Thank You to the Organizers for a
Scholarly and Dignified Conference