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

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

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

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: 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: 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 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 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.

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 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

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

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