1. Etiology of Acute Kidney Injury in Neonates
9th International pCRRT Conference on
Pediatric Continuous Renal Replacement Therapy
August 31-September 2, 2017
Etiology of Acute Kidney Injury in Neonates
Jordan M. Symons, MD
University of Washington School of Medicine
Seattle Children’s Hospital
Seattle, WA

2. 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

3. 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?

4. Neonatal Physiology with Implications for the Kidney

5. Development Has an Effect on Renal Function
Human nephrogenesis is complete by weeks gestation
Nephron maturation continues after birth
GFR low in newborn; increases with time
Different renal function depending on gestational age, postnatal age, development, clinical scenario

6. GFR is Low in the Newborn
Transition to post-natal status favors flow to lungs
High renal resistance at birth
Even lower GFR in preterm infant

7. Delayed Renal Stabilization in Preterms
Not in steady state

8. GFR is Low in the Newborn
Premature Infant
Term Infant

9. 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+

10. 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

11. 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

12. Water Loss by Gestational Age and Chronological Age
Hartnoll, Sem Neonatol, 2003(8):

13. Neonatal Renal Risks from Clinical Conditions

14. 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

15. We have known this for a while . . .

16. Perinatal Factors Associated with AKI

17. AKI After Congenital Heart Surgery
430 infants
<90 days (median 7d)
34w – term
Median weight 3.1kg
Heart surgery for congenital defects
Blinder et al. J Thorac Cardiovasc Surg 2012

18. AKI After Congenital Heart Surgery
PostOp AKI: N=225
Stage 1
Stage 2
Stage 3
Blinder et al. J Thorac Cardiovasc Surg 2012

19. Neonatal AKI from Nephrotoxin Exposure
107 VLBW infants over 1 year ( )
93 (87%) exposed to at least one nephrotoxic medication
Mean number of meds: 1.64
Median number of meds: 2
AKI rate in study: 28/107 (26%)
All were exposed to nephrotoxic meds; those without nephrotoxins did not get AKI
Rhone et al. J Matern Fetal Neo Med 2014

20. ECMO and Neonatal AKI ECMO patients particularly prone to AKI
Critically ill
Inflammatory response with ECMO
High rates of AKI
Zwiers (Crit Care 2013): 64% AKI
Gadepalli (J Pediatr Surg 2011): 71% AKI

21. Physiology
AKI
Illness
Interventions
Prematurity

22. Etiology AKI in Neonates: Summary
Neonatal AKI has become more common with advancing critical care
Numerous factors contribute
Physiology, development, illness, therapies
Certain neonates are at increased risk
High index of suspicion is needed

23. Thank You for Your Attention!