Major Clinical Trials in AKI Michael Zappitelli, MD, MSc Montreal Children's Hospital McGill...
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Transcript of Major Clinical Trials in AKI Michael Zappitelli, MD, MSc Montreal Children's Hospital McGill...
Major Clinical Trials in AKI
Michael Zappitelli, MD, MScMontreal Children's HospitalMcGill University Health Centre
What does “Clinical Trials in AKI” mean?
Illness AKI
Reduce AKITherapeuticsPreventative
RRT need
Reduce RRT needTherapeutics Preventative
Good vs. poor outcome
RRT intervention evaluationModality“Dose”TimingIntra/Post-RRT therapeutics?
ATN Study
Timing not standardizedDid it really answer the dose question? Allowed for different modalities
No benefit to increase HD dose > 3/week + Kt/V >1.2-1.4 ORCRRT > 20 ml/kg/hr
RENAL study
Timing not standardized
Modality not addressed
Meta-analyses: similar findings
Several meta-analyses: intensity and/or renal recovery
Casey et al, Renal Failure, 2010Zhang et al, J of Critical Care, 2010Jun et al, CJASN, 2010Negash et al, Cochrane review, updated 2011
Modality - several meta-analyses: IHD vs CRRT
Tonelli et al, AJKD, 2002Rabindranath, Cochrane review, 2008Bagshaw et al, Crit Care Med, 2008
Highlight: Poor quality evidence, heterogeneity
Timing and dose
“Early”: within 12 hours of inclusion“Late”: when “standard” RRT criteria used
“High”: ~40 ml/kg/hr for 70kg“Low”: ~ 15-20 ml/kg/hr for 70 kg
Timing and dose
Only 2 actual RCT’s
Heterogeneity high
Timing and dose: pediatric
20 children: +24 hours PD vs not
No differences in biomarkers
22 children: prophylactic PD vs. not
Timing and dose: horizon
IDEAL study: Early (12 hours from AKI) vs. later (>48 hours from AKI) RRT initiation. N=864
STAART-AKI: NGAL used for eligibility. Accelerated (<12 hours from eligibility) vs. not.
Pediatric:Use of biomarkers to trigger /decision on CRRT and fluid management
Diuretics: do they help once CRRT stopped?
They excreted more sodium No difference in renal recovery
Can we prevent/treat AKI?Still an elusive goal.
Therapeutic hypothermia
Off pump versus on pump (cardiac surgery)
Statins
Sodium bicarbonate
Anti-inflammatory agents
Fenoldopam, ANP/BNP
RIPC, theophylline
Remote ischemic pre-conditioning
Remote ischemic pre-conditioning
Child Remote Ischemic Preconditioning
Creat Estimated GFR Plasma CysC
Plasma NGAL Urine NGAL Urine OutputNo effect
Too low power
?Significance of preventing 50% SCr rise?
Theophylline: the only KDIGO recommended drug
Recent trials: adult CIN
Theophylline: urine outputJenik
Bhat
Theophylline: GFRBhat Bakr
AKI treatments: horizon
Ongoing or planned or completed
Aminophylline
Acetaminophen
RIPC
Intensive glucose control
Rewarming
Summary & ConclusionDose/Intensity of RRT:
ATN/RENAL study suggest intensity above ~ 20-25 ml/kg/hr willnot improve outcomes
No pediatric data, but:Should we be more aware of the dose we provide?Are we actually delivering what we think we are?Modality based on clinical factors
Use of diuretics to enhance water clearance unlikely to improveoutcome or prevent RRT need
Does not mean they do not play important role
“Earlier” RRT initiation may be beneficialNeed to standardize definitionPediatrics: different epidemiology, fluid overload – future trials
Summary & Conclusion
Clinical trials in pediatrics ARE feasible
Need to sort out: Existing practice Best outcome to study Best population to study Balance risk of Rx vs potential benefit Demonstrate clinical equipoise
What are the most important first questions we want to answer?
THANK YOU
pCRRT conference organizers
Montreal Children’s Hospital AKI research team
Collaborators/mentors:Stuart Goldstein, Prasad Devarajan, Chirag Parikh
The Kidney Injury During Membrane Oxygenation group