Pediatric Acute Kidney Injury: Supportive Therapies

1. Pediatric Acute Kidney Injury: Supportive Therapies Jordan M. Symons University of Washington School of Medicine Seattle Children’s Hospital

2. Stage-Based Management of AKI Kidney Intl Supplements (2012) 2: 19-36

3. Natural History of Acute Kidney Injury (AKI)

4. What Goes Wrong in AKI? Volume issues • Volume overload • Pulmonary edema • Tissue edema • Congestive heart failure • Hypertension (+/-) Metabolic issues • Chemical imbalance • Hyperkalemia • Metabolic acidosis • Hyperphosphatemia • Hyponatremia • “Uremic” symptoms

5. Conservative Management of Established AKI: Diuretics • Increase urine output • Improve fluid balance • Permit delivery of fluid to patient • Nutrition, other therapies • May augment loss of potassium

6. Bagshaw CCM 2008 36(4) Do Diuretics Help in AKI? 1. Majority of ICU patients get diuretics 8 non-randomized studies 2. But no improvement in clinical outcomes 6 randomized studies

7. Management of Established AKI: Pharmacotherapy Attempted Therapies Definitive Therapies Hmmmm . . . . . • Diuretics • Mannitol • Dopamine • Fenoldopam • Glucocorticoids • Atrial natriuretic peptide • N-acetylcysteine (other than contrast-induced AKI

8. 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

9. Kolff Rotating Drum Kidney: 1940s

10. From Patient • ~20 meters of sausage casing (2.4m2) • Prime volume 2 liters • Clearance 140 – 170 ml/min Back To Patient First 16 patients died

11. Goals of Renal Replacement Therapy (RRT) • Restore fluid, electrolyte and metabolic balance • Remove endogenous or exogenous toxins as rapidly as possible • Permit needed therapy and nutrition • Limit complications

12. RRT Options in AKI • Hemodialysis, Peritoneal Dialysis, CRRT • Each has advantages & disadvantages • Modality choice guided by • Patient Characteristics • Disease/Symptoms • Hemodynamic stability • Goals of therapy • Fluid removal, electrolyte correction, or both • Availability, expertise and cost Walters et. al. Pediatr Nephrol 2008

13. Hemodialysis • Blood perfuses extracorporeal circuit • Machine mixes dialysate on-line • High efficiency system • Requires vascular access; anticoagulation • Technically complex • May be poorly tolerated by critically ill patient Time Remaining: 1:30 Blood Flow Rate: 300 ml/min Dialysate Flow Rate: 500 ml/min Ultrafiltration Rate: 0.3 L/hr Total Ultrafiltrate: 1.5 L/hr

14. Peritoneal Dialysis Dialysate Peritoneal Space Effluent Collection • Sterile dialysate introduced into peritoneal cavity through a catheter • Possibly better tolerated • Lots of pediatric experience in chronic setting • Low efficiency system • Risk for infection

15. Continuous Renal Replacement Therapy (CRRT) Rinse-O-Matic 3000 • Common ICU modality • Technically similar to HD • SLOW: ?Better tolerated by ICU patient? • CONTINUOUS: Preserve metabolic stability; maintain fluid balance for oliguric patients who require high daily input (IV medications, parenteral nutrition)

16. RRT for AKI: Which Modality is Best? In-hospital mortality No Difference in Survival Rabindranath et al., Cochrane Database of Systematic Reviews (2007)

17. RRT for AKI: Which Modality is Best? Years of study: 1992-1998 N=226; Mean age 6y; Mean wt 25kg P<0.01 (HD vs other) Bunchman et al., PediatrNephrol (2001) 16:1067–1071

18. Overall survival was 58% across all centers CJASN 2007 2:732-8

19. Impact of Volume Overload Goldstein SL et al: Pediatrics 2001 Gillespie R et al: PediatrNephrol 2004 Foland JA et al: Crit Care Med 2004 N=113 *p=0.02; **p=0.01 “Volume Overload is the Enemy” Sutherland et al: AJKD 2010 Hazard Ratio 3.02 (1.50-6.10) Kaplan-Meier survival estimates, by percentage fluid overload category

20. Hazard Ratio (95% CI)‏ Group 1 Group 2 Group 3 1 0.51 (0.35-0.72)‏ 0.49 (0.35-0.69)‏ Higher Dose: A Better Outcome? N=425 Group 1: 20ml/kg/hr Group 2: 35ml/kg/hr Group 3: 45ml/kg/hr Ronco, et al. Lancet 2000

21. Intensity of Renal Replacement in AKI: No Difference? VA/NIH Acute Renal Failure Trial Network, NEJM, 2008 RENAL Replacement Therapy Study Investigators, NEJM, 2009

22. CRRT Dose N Survivors Hazard Ratio (95% CI)* Low Dose <25.6ml/kg/hr 43 23 0.810 (0.418-1.57) High Dose >25.6ml/kg/hr 44 17 1.23 (0.637-2.39) High Dose of CRRT for Pediatric Patients *p=0.533 Gillespie, Pediatr Nephrol 2004

23. RRT: Effective But Not Perfect Strengths Weaknesses Adapted equipment Nothing specific for smaller children No auto-feedback Targets programmed by provider “Blunt” metabolic control Hard to fine-tune Does not effectively address immune issues • Volume control • Fluid removal from vascular compartment • Metabolic control • Electrolyte removal • Uremic retention molecule removal

24. A Dedicated Neonatal CRRT Machine? • Lines and filters to limit extracorporeal blood volume • Hardware and software accurate for low flows and low UF volumes • Dedicated rather than adapted • Safe and reliable Claudio Ronco with the Cardio Renal Pediatric Dialysis Emergency Machine (CARPEDIEM)

25. Summary • Current approach to AKI is supportive, addressing issues after AKI established • PD, HD, and CRRT can all have a role • Clear ability to control volume • Evidence for metabolic control • Goals for dose in AKI remain unclear • New technology may offer opportunities for broader application & improved care

26. Early dialysis with Kolff artificial kidney, Mt Sinai Hospital, New York, 1948