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Does CRRT Improve Renal Recovery and Outcomes ? UK Kidney Research Keynote Lecture

This keynote lecture discusses the impact of Acute Kidney Injury (AKI) in the pediatric intensive care unit (PICU) and compares different renal replacement therapies. It explores the benefits and implications of continuous renal replacement therapy (CRRT) along with other techniques.

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Does CRRT Improve Renal Recovery and Outcomes ? UK Kidney Research Keynote Lecture

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  1. Does CRRT Improve Renal Recovery and Outcomes?UK Kidney Research Keynote Lecture Patrick D Brophy, MD, MHCDS Director Pediatric Nephrology Professor The University of Iowa London 2015

  2. UnEqual

  3. Many questions remain unanswered • What therapy should we use? • When should we start it? • What are we trying to achieve? • How much therapy is enough? • When do we stop/switch? • Can we improve outcomes? • Throughout the conference these are the basic questions we have tried to address!

  4. Overview • Impact of Acute Kidney Injury in the PICU • Therapies Comparison in brief • IRRT, CRRT & Hybrid therapies -SLEDD • Solute clearance with IRRT v CRRT v SLEDD • Dose-outcome relationships & IRRT v CRRT • Summary & thoughts

  5. Pediatric AKI: Definition Past: So many definitions…. Risk Injury Failure End-Stage Kidney Disease (RIFLE) Pediatric RIFLE (pRIFLE) Acute Kidney Injury Network definition Crit Care. 2005; 9(5): 523–527

  6. Pediatric AKI: Incidence in PICUPopulation & Definition-dependent • Cardiac Surgery N=395 N = 395 AKI: 21% AKI: 34% Anesth Analg 2009;109:45–52 (Aprotinin study) Kidney Int. 2009 Oct;76(8):885-92

  7. Pediatric AKI: Incidence in PICUPopulation & Definition-dependent • General PICU Most Critically ill children Vasopressors/Ventilated Urinary catheter All PICU Admx SCr baseline All PICU stay>48hrs SCr Doubling (pRIFLE I) pRIFLE pRIFLE 82% AKI 4.5% AKI 42% AKI Kid Int 2007; 71: 1028-35 Pediatr Crit Care Med 2007; 8:29 –35 Al-Kandari et al, ASN, 2008

  8. Pediatric AKI:Changing Epidemiology Previously: Primary renal diseases Stickle SH et al: Am J Kid Dis 45:96-101, 2005

  9. CRRT Diagnoses

  10. RRT Options • Hemodialysis, Peritoneal Dialysis, CRRT, SLEDD • Each has advantages & disadvantages • Choice is guided by • Patient Characteristics • Disease/Symptoms • Hemodynamic stability • Goals of therapy • Fluid removal • Electrolyte correction • Both • Availability, expertise and cost Pediatr Nephrol (2009) 24:37–48

  11. Trends in Pediatric RRT CRRT Increasing 12-US Multicentre ppCRRT Most include Dialysis Warady et al, PediatrNeph 2000, 15:11-3

  12. Why CRRT? • Reduces hemodynamic instability preventing secondary ischemia • Precise Volume control/immediately adaptable • Uremic toxin removal • Effective control of uremia, hypophosphatemia, hyperkalemia • Acid base balance • Rapid control of metabolic acidosis • Electrolyte management • Control of electrolyte imbalances • Allows for improved provision of nutritional support • Management of sepsis/plasma cytokine filter • Safer for patients with head injuries

  13. Indications for Pediatric RRT • Electrolyte (metabolic) imbalance • Uremia with bleeding and or encephalopathy • Acuity/Degree of Kidney Injury • reduction in GFR/elevated creatinine • reduction in urine output • Nutritional support • Intoxications, Inborn errors of Metabolism (IEM) • Fluid Overload (hypervolemia with pulmonary edema/respiratory failure)

  14. Implications of the available data

  15. Major Renal Replacement Techniques Intermittent Hybrid Continuous IHD Intermittenthaemodialysis SLEDD Sustained (or slow) low efficiency daily dialysis CVVH Continuous veno-venous haemofiltration IUF IsolatedUltrafiltration CVVHD Continuous veno-venous haemodialysis SLEDD-F Sustained (or slow) low efficiency daily dialysis with filtration CVVHDF Continuous veno-venous haemodiafiltration SCUF Slow continuous ultrafiltration

  16. Intermittent Therapies - PRO

  17. Intermittent Therapies - CON

  18. Intradialytic Hypotension:Risk Factors • Age < 5, weight < 10 kg • Pressor requirement, Low Predialysis SBP • Cardiac disease- congenital repairs • Poor nutritional status / hypoalbuminaemia • Uremic neuropathy or autonomic dysfunction • Severe anemia • High volume ultrafiltration requirements

  19. Managing Intra-dialyticHypotension • Dialysate temperature modeling • Low temperature dialysate • Dialysate sodium profiling • Hypertonic Na at start decreasing to 135 by end • Prevents plasma volume decrease • Midodrine if not on pressors • UF profiling • Colloid/crystalloid boluses • Reducing dosing 2005 National Kidney Foundation K/DOQI GUIDELINES

  20. Continuous Therapies - PRO ** Depends on strategy and management

  21. Continuous Therapies - CON

  22. SLED(D) & SLED(D)-F :Hybrid therapy • Conventional dialysis equipment • Online dialysis fluid preparation • Excellent small molecule detoxification • Cardiovascular stability maybe as good as CRRT • Reduced anticoagulation requirement • Decreased costs compared to CRRT? • Phosphate supplementation required like CRRT Fliser, T & Kielstein JT. Nature Clin Practice Neph 2006; 2: 32-39 Berbece, AN & Richardson, RMA. Kidney International 2006; 70: 963-968

  23. Uremia Control Liao, Z et al. Artificial Organs 2003; 27: 802-807

  24. Large molecule clearance Liao, Z et al. Artificial Organs 2003; 27: 802-807

  25. Comparison of IHD and CVVH John, S & Eckardt K-U. Seminars in Dialysis 2006; 19: 455-464

  26. RRT for Acute Kidney Injury • There is some evidence for a relationship between higher therapy dose and better outcome, at least up to a point • This is true for IHD* and for CVVH** • There is nodefinitive evidence forsuperiority of one therapy over another, and wide practice variation exists*** • Accepted indications for RTT vary • No definitive evidence on timing of RRT *Schiffl, H et al. NEJM 2002; 346: 305-310 ** Ronco, C et al. Lancet 2000; 355: 26-30 *** Uchino, S. Curr Opin Crit Care 2006; 12: 538-543

  27. Therapy Dose in IRRT p = 0.01 p = 0.001 Schiffl, H et al. NEJM 2002; 346: 305-310

  28. Therapy Dose in CVVH • The “Ronco Study” • Improved survival in all patients with convective clearance of 35mL/kg/hr • Trend towards improved survival in septic patients with convective clearance of 45mL/kg/hr Ronco, C et al. Lancet 2000; 355: 26-30

  29. The “ATN Study” • 1124 adults in the ICU • 563 had intensive therapy • 561 had less-intensive therapy

  30. ATN Study

  31. ATN Study

  32. Intensity of CRRT in Critically Ill Patients (The “RENAL” Study) NEJM 361(17); Oct 2009

  33. Intensity of CRRT in Critically Ill Patients (The “RENAL” Study) NEJM 361(17); Oct 2009

  34. Outcome with IRRT vs CRRT • Trial quality low: many non-randomized • Therapy dosing variable • Illness severity variable or details missing • Small numbers • Uncontrolled technique, membrane • Definitive trial would require 660 patients in each arm! • Unvalidated instrument for sensitivity analysis “there is insufficient evidence to establish whether CRRT is associated with improved survival in critically ill patients with ARF when compared with IRRT” Kellum, J et al. Intensive Care Med 2002; 28: 29-37

  35. Outcome with IRRT vs CRRT • No mortality difference between therapies • No renal recovery difference between therapies • Unselected patient populations • Majority of studies were unpublished Tonelli, M et al. Am J Kidney Dis 2002; 40: 875-885

  36. Outcome with IRRT vs CRRT Vinsonneau, S et al. Lancet 2006; 368: 379-385

  37. Summary • There is some evidence for a relationship between higher therapy dose and better outcome for IHD • There is nodefinitive evidence forbeneficial effects of high dose CRRT despite major attempts to do so • Trials have demonstrated it is difficult to deliver this dose due to unpredictable breaks in treatment-clotting, bag changes, nursing (Vesconi 2009) • Modern IHD approaches may reduce overt hemodynamic instability even in unstable ITU patients • CRRT greater exposure to anticoagulation *Schiffl, H et al. NEJM 2002; 346: 305-310 ** Ronco, C et al. Lancet 2000; 355: 26-30 *** Uchino, S. Curr Opin Crit Care 2006; 12: 538-543

  38. Summary • RCT (Uchino 2009) 3-5% incidence of significant bleeding problems as opposed to 1% with IHD • HIT • Filter downtime up to 8 hours per day due to clotting problems and short filter life • Delayed procedures, tests,surgery • The legion of alternatives used emphasize the problem **citrate looks promising • Costs– although this is variable (Srisawat N et al. Crit Care. (2010))

  39. Approach to Pediatric AKI Defend Blood Pressure Restore & Optimize Perfusion Use inotropes with care Mitigate Inflammatory Injury Optimize RRT EGDT Normal Increasedrisk Damage  GFR Kidneyfailure Death Antecedents Intermediate Stage AKI Outcomes

  40. Reference Tools • Adqi.net-web site for information on CRRT • Crrtonline.com-web site for info on Dr Mehta’s meeting • www.PCRRT.com Pediatric CRRT with links to other meetings, protocols, industry • PCRRT list serve (contact Bunchman)

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