Renal dysfunction is common in neonates on Extra Corporeal Membrane Oxygenation

1. Renal dysfunction is common in neonates on Extra Corporeal Membrane Oxygenation Alexandra J.M. Zwiers Pediatric Nephrology & Intensive Care Erasmus MC - Sophia Children’s Hospital Rotterdam, The Netherlands

2. Erasmus MC – Sophia Children’s Hospital Extra Corporeal Membrane Oxygenation (ECMO) facility since 1993 All age groups of children & diagnoses Total number of ECMO runs > 460 Annual number of ECMO runs ± 35

3. Rationale I Renal dysfunction • Decreased blood pressure • Insufficient tissue perfusion • Hypoxia/Ischemia • Nephrotoxic drugs • Incidence Acute Kidney Injury in critically ill infants ranges from 8% to 60%¹ ² ³ • Incidence of renal dysfunction in ECMO patients..? ¹Andreoli et al. Pediatr Nephrol 2009 24:253-263 ²Askenazi DJ et al. Pediatr Nephrol. 2009 24;265-274 ³Akcan-Arikan A et al. Kidney Int. 2007 May;71(10):1028-35

4. Rationale II • Early detection of renal dysfunction has implications for the child’s treatment in the short term • 50% of the survivors of childhood Acute Kidney Injury on the ICU have signs of Chronic Kidney Disease 3 to 5 years after the initial event4 4Askenazi DJ et al. Kidney Int. 2006 Jan;69(1):184-9

5. Aim of the study To determine the incidence of renal dysfunction in neonates treated with ECMO using two methods: Maximal serum creatinine per patient during ECMO treatment Mean serum creatinine level per patient by means of a Z-score Compared with recently collected serum creatinine reference values in our hospital.4 4Boer et al. Pediatr Nephrol 2010, In press

6. Methods • All patients treated with ECMO before routine use of CVVH • Inclusion Criteria: • Treated with ECMO in our center • Age at start of ECMO max 30 days • Exclusion Criteria: • Died within one week after ECMO • Pre-existent renal anomalies Statistics: Z-score, ANOVA • Clinical data from our patient data management system (PDMS) over a 6- year period, from 1996 until 2002

7. Results l 125 Neonates treated with ECMO of whom 90 survived (72%)

8. Results ll Primary Diagnosis *Majority of the patients had severe Persistent Pulmonary Hypertension

9. Results llI - Maximal level of creatinine Forty patients (44%) showed at least one serum creatinine level (median value 62 [10 -166]) above P97.5 for age Median time of 43 hours [5 - 222 hours] after start of ECMO Compared with: Serum creatinine reference values4 4Boer et al. Pediatr Nephrol 2010, In press

10. Results IV - Individual Z-scores of Creatinine Z-scores are calculated, based on serum reference values4 Z-score: Tells how the data- point compares to normal data 4Boer et al. Pediatr Nephrol 2010, In press

11. Results V – ANOVA Serum Creatinine Mixed Model ANOVA with 95% Confidence Interval Z-score: Mean Z-values per ECMO day

12. Results VII - Serum creatinine ≥ 2 SD N=84 N=80 N=72 N=68 N=58 N=37 N=35 N=27 N=17 N=14 N=12 N=8 N=3 N=3

13. Conclusion Renal dysfunction is common in neonates treated with ECMO!

14. Limitations • Retrospective cohort study • Renal dysfunction is diagnosed by measuring serum creatinine, which is not considered the golden standard

15. Discussion “Awareness” of renal dysfunction may result into rapid adjustment of dosage of drugs eliminated by the kidneys: Studying Chronic Kidney Disease in children with renal dysfunction during ECMO treatment is indicated • To avoid accumulation • To avoid nephrotoxic drugs

16. Acknowledgements S.N. de Wildt¹, MD PhD W.C.J. Hop², MSc PhD K. Cransberg¹, MD PhD D. Tibboel¹, MD PhD ¹Pediatric Nephrology & Intensive Care, ErasmusMC - Sophia Children’s Hospital ²Department of Biostatistics, ErasmusMC, Rotterdam, The Netherlands Funding: Sophia Foundation Scientific Research, Grant application number: 633

18. Statistics lV • Mean Z-scores of all patients who have been treated with ECMO Died during ECMO Survived ECMO