9 th International p CRRT Conference on Pediatric

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

Neonatal AKI: How Do We Define It?

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: What Interventions Do We Have?

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

Renal Replacement Therapy for Neonatal AKI A New Era in Neonatal CRRT

Neonatal AKI: What About Outcomes?

Low Birthweight and AKI Study Population Results Koralkar 1 VLBW (N=229) AKI incidence 18% Mortality 42% vs. 5% without AKI HR for death 9. 3 (95% CI 4. 1 -21. 0) Viswanathan 2 ELBW (N=472; 46 AKI, 46 matched controls) AKI incidence 12. 5% overall (59/472) Case mortality rate 70% in cases vs. 22% in controls Carmody 3 VLBW (N=455) AKI incidence 39. 8% More common in sicker infants (CRIB score <10) More common in most premature (gest age <28 w) OR for death 4. 0 (95% CI 1. 4 -11. 5) 1. Koralkar et al. Pediatr Res 2011 2. Viswanathan et al. Pediatr Nephrol 2012 3. Carmody et al. CJASN 2014

ECMO and AKI Study Population Results Gadepalli 1 All congen DH patients on ECMO from 1999 -2009 (N=68) AKI incidence 71% Those with highest level of AKI: • Lower survival (27% vs 80%; P=0. 001) • Longer ECMO (314 + 145 vs 197 + 115 hr; P=0. 001) • Fewer vent-free days in first 60 days of illness Zwiers 2 All neonates over 14 year period placed on ECMO (N=242) Overall survival 74% AKI incidence 64% Those with highest level of AKI: • Lower survival to ICU discharge (35%) compared to milder AKI or no AKI (76 -82% survival) 1. Gadepalli et al. J Pediatr Surg 2011 2. Zwiers et al. Crit Care 2013

Heart Surgery and AKI Study Population Results Blinder 1 Infants <90 d old undergoing surgery for CHD (N=430) AKI incidence 52% More severe AKI associated with mortality • Stage 2: OR 5. 1 (95% CI 1. 7 -15. 2) • Stage 3: OR 9. 46 (95% CI 2. 91 -30. 7) AKI also associated with longer ICU stay Al Abbas 2 Infants <28 d old undergoing surgery for CHD (N=122) AKI incidence 62% Stage 3 AKI associated with: • Mortality: OR 6. 7 (95% CI 1. 08 -41. 50) • Longer ICU stay: HR 9. 09 (95% CI 1. 35 -60. 95) 1. Blinder et al. J Thorac Cardiovasc Surg 2012 2. Al Abbas et al. Pediatr Nephrol 2013

Neonatal AKI in a PICU Population • • N=80 <28 d old Gest age 38 w AKI 35%; more common with – Younger infant – Bacteremia – Higher serum sodium Kriplani et al. PCCM 2016

pp. CRRT Data of Infants <10 kg: Survival by Weight Group Askenazi et al. J Ped 2013

pp. CRRT Data of Infants < 1 Month: Overall Survival N=35

pp. CRRT Data of Infants < 1 Month: Survival by Disease Category 73% 25% 0 0 33% 100% 33% Totals: N=35 Survivors=15

Therapeutic Hypothermia: Protective Against AKI? • Hypothermia standard of care for term infants with perinatal asphyxia • RCT of 120 term infants (N=60 each) Therapeutic Hypothermia AKI Standard Therapy AKI 19 41 No AKI Tanigasalam et al. J Matern-Fetal Neo Med 2016 36 24 No AKI

Neonatal AKI: What’s the Long-Term Outlook?

Risk for CKD After AKI • Growing recognition of risk • Mammen et al. (AJKD 2012) – Up to 3 -year follow-up for survivors of pediatric AKI in the ICU – Markers of CKD • Albuminuria; GFR; blood pressure

Risk for CKD After AKI • CKD (low GFR or albuminuria) ~10% • Risk of CKD (GFR 60 -90; HTN; hyperfiltration) ~47% Mammen et al. AJKD 2012

Likelihood of Renal Recovery in Very Small Infants with AKI • Retrospective review of 20 infants – ELBW, AKI (mean Cr 2. 9), up to 18 -yr F/U – Compared those with later CKD to normals • 9/20 patients went on to develop CKD: – Risk factors for progression: • Urine Pr/Cr >0. 6 at 1 yr • Cr >0. 6 mg/d. L at 1 yr • BMI >85 th percentile Abitbol et al, Pediatr Nephrol 18: 887, 2003

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!

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Thank You for Your Attention!