1. University of Alabama at Birmingham
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

2. Precision Medicine Takes into account individual differences
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

3. How Does Precision Medicine Apply to RRT?
Focus of ADQI 17 International Consensus Conference on CRRT: Precision Renal Replacement Therapy
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

4. Patient Selection and Timing: Factors to Consider for RRT Initiation
Macedo E, Mehta RL: Continuous dialysis therapies: core curriculum Am J Kidney Dis 2016.

5. Patient Selection and Timing of RRT: Demand vs. Capacity
Consensus statement:
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.

6. Patient Selection and Timing of RRT: Demand vs. Capacity
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.

7. Factors Affecting Metabolic and Fluid Demand
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.

8. RRT Support Based on Demand vs. Capacity
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.

9. Precision Fluid Management in CRRT
Fluid management is a dynamic process
Goal:
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.

10. Precision Fluid Management in CRRT
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.

11. Precision Fluid Management in CRRT
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.

12. Precision Solute Control in CRRT
Current clinical guidelines recommend static prescribed dose of 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
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.

13. Precision Solute Control in CRRT
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.

14. Precision Solute Control in CRRT
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.

15. Precision Solute Control in CRRT
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.

16. Role of Technology for Management of AKI
AKI management is a continuum from detection to treatment
AKI Management must include continuous re-evaluation 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.

17. Role of Technology for Management of AKI
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.

18. Role of Technology for Management of AKI
Results of ADQI 17th Conference on CRRT. Blood Purif 2016; 42.

19. 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.

20. Extracorporeal Blood Purification (EBT)
Convective Therapies
HVHF
High Cut-off
Hybrid Therapies
CPFA
Perfusion / Adsorptive Therapies
Non-selective membranes
Semi-selective membranes
Polymyxin B [PMX]
Cytokine-adsorptive columns
Other Therapies
Renal tubular assist device (RAD)
Selective cytopheretic devices (SCD)
Liver support / MARS
ECCOR / ECMO
Adapted from Forni et al. Seminars in Nephrology, Vol35,No1,January 2015,pp55–63

21. 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

22. 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

23. 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

24. HVHF for Septic AKI
Clark E, et al. Crit Care 2014

25. Results No mortality reduction with HVHF
No reduction in vasopressor requirements
No difference in renal recovery
Clark E, et al. Crit Care 2014

26. 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

27. Early HVHF vs. Standard Care for Post–Cardiac Surgery Shock: HEROICS Study
Combes et al. AJRCCM, Vol. 192, No. 10 (2015), pp

28. 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

29. SETTING & PARTICIPANTS:
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