Download Precision Renal Replacement Therapy

What’s New in RRT for AKI:
Precision Renal Replacement Therapy
2016 ADQI 17 Consensus Conference on CRRT
Ashita Tolwani, MD, MSc
Professor of Medicine
University of Alabama at Birmingham
2016
Precision Medicine
 Takes into account individual differences
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Variations in genes
Environment
Lifestyle
 Targets specific treatments of illnesses by selecting
different drugs and doses
 Tailors medical decisions and practices to the
individual patient
How Does Precision Medicine Apply to RRT?
 Focus of ADQI 17 International Consensus Conference
on CRRT: Precision Renal Replacement Therapy
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Patient Selection and Timing
Precision Fluid Management in CRRT
Precision CRRT and Solute Control
Role of Technology for Management of AKI
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42
Patient Selection and Timing:
Factors to Consider for RRT Initiation
Macedo E, Mehta RL: Continuous
dialysis therapies: core curriculum
2016. Am J Kidney Dis 2016.
Patient Selection and Timing of RRT:
Demand vs. Capacity
 Consensus statement:
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Acute RRT should be considered when metabolic and
fluid demands exceed total kidney capacity
Individualized decision to start
Not based solely on renal function or AKI stage
 Kidneys have finite capacity
 RRT Initiation based on ability of kidney to meet
demands
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
Patient Selection and Timing of RRT:
Demand vs. Capacity
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
Factors Affecting Metabolic and Fluid Demand
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
RRT Support Based on Demand vs. Capacity
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
Precision Fluid Management in CRRT
 Fluid management is a dynamic process
 Goal:
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Maintenance of the patency of the CRRT circuit
Maintenance of plasma electrolyte and acid-base
homeostasis
Regulation of patient fluid balance
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
Precision Fluid Management in CRRT
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
Precision Fluid Management in CRRT
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
Precision Solute Control in CRRT
 Current clinical guidelines recommend static prescribed
dose of 20-25 ml/kg/hr
 Clinical trials evaluated only fixed dose prescriptions
 Uncertain fixed/static dose is appropriate for critically
ill patients
 New focus of CRRT prescription
Based on concept of dynamic solute control
 Adapted to changing clinical needs of critically ill
patients
 Addition of quality measures specific for monitoring
delivered dose
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Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
Precision Solute Control in CRRT
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
Precision Solute Control in CRRT
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
Precision Solute Control in CRRT
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
Role of Technology for Management of AKI
 AKI management is a continuum from detection to
treatment
 AKI Management must include continuous reevaluation of treatment prescription and delivery
 Integration of IT tools in practice of CRRT is
recommended to improve practice and patient care
 Continuum of AKI must include a feedback loop for
prescription reassessment after monitoring, data
collection and evaluation of the delivered treatment
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
Role of Technology for Management of AKI
Results of ADQI 17th Conference on
CRRT. Blood Purif 2016; 42.
Role of Technology for Management of AKI
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
Role of Technology for Management of AKI:
Other Therapies
 No evidence for specific extracorporeal therapies
 HVHF not recommended for sepsis
 Precision therapy should be considered whenever
possible based on theoretical advantages of specific
techniques
 CRRT technology should be seen as integrated system
that provides multiple organ support therapy (MOST)
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.
Extracorporeal Blood
Purification (EBT)
Convective
Therapies
Hybrid
Therapies
HVHF
CPFA
Perfusion /
Adsorptive
Therapies
High Cut-off
Non-selective
membranes
Semi-selective
membranes
Polymyxin B
[PMX]
Cytokineadsorptive
columns
Adapted from Forni et al. Seminars in Nephrology,
Vol35,No1,January 2015,pp55–63
Other
Therapies
Renal tubular
assist device
(RAD)
Selective
cytopheretic
devices (SCD)
Liver support /
MARS
ECCOR / ECMO
High Volume Hemofiltration (HVHF)
 HVHF is defined as UF rate > 35 mL/Kg/hr
 Pulse HVHF is defined as UF rate > 100–120 ml/kg/hr
for a short period of 4–8 h, followed by conventional
CVVH
 May achieve clinically meaningful convective and
adsorptive removal of inflammatory mediators
HVHF for Septic AKI:
A Systematic Review and Meta-analysis
 Objective:
 To evaluate the effects of HVHF compared with SVHF for
septic AKI
 Methods:
 Publications between 1966 and 2013
 RCTs that compared HVHF (effluent rate >50 ml/kg/hr) vs.
SVHF in the treatment of sepsis and septic shock
Clark E, et al. Crit Care 2014
HVHF for Septic AKI:
A Systematic Review and Meta-analysis
 Primary outcome: 28-day mortality
 Secondary outcomes:
 Recovery of kidney function
 Lengths of ICU and hospital stay
 Vasopressor dose reduction
Clark E, et al. Crit Care 2014
HVHF for Septic AKI
Clark E, et al. Crit Care 2014
Results
 No mortality reduction with HVHF
 No reduction in vasopressor requirements
 No difference in renal recovery
Clark E, et al. Crit Care 2014
HVHF vs. SVHF for Septic Shock Patients with
AKI (IVOIRE study): A Multicentre RCT
• 140 Patients with septic shock and AKI randomized
to CVVH: 70 mL/kg/hr vs. 35 mL/kg/hr
• RF pre- and post- 1/3-2/3
• BF 200 – 320 mL/min
• Anticoagulation: UFH
• Trial stopped early and underpowered
HVHF group:
• Higher incidence of
hypophosphatemia
• Higher incidence of hypokalemia
• Underdosing of antibiotics
Joannes-Boyau et al. Int Care Med. 2013
Early HVHF vs. Standard Care for Post–Cardiac
Surgery Shock: HEROICS Study
Combes et al. AJRCCM, Vol. 192, No. 10 (2015), pp. 1179-1190
Results
 Early HVHF did not lower Day-30 mortality and did not impact
other important patient-centered outcomes compared with
delayed CVVHDF initiation for patients with persistent, severe AKI
 HVHF patients
 Faster correction of metabolic acidosis
 Tended to be more rapidly weaned off catecholamines
 More frequent hypophosphatemia, metabolic alkalosis, and
thrombocytopenia
High-Dose vs. Conventional-Dose CVVHDF and
Patient and Kidney Survival and Cytokine Removal in
Sepsis-AKI: A RCT
 SETTING & PARTICIPANTS:
 Septic patients with AKI receiving CVVHDF for AKI
 Sepsis defined according to the ACCP/SCCM consensus
conference criteria
 AKI defined as a level greater than the Injury stage of RIFLE
 212 patients randomized
 INTERVENTION:
 Conventional (40mL/kg/h) & high (80mL/kg/h) doses of CVVHDF
 OUTCOMES:
 Patient and kidney survival at 28 and 90 days, circulating
cytokine levels
HICORES Investigators. Am J Kidney Dis. 2016