Who? Dialysis for Acute Renal Failure: Who, What, How, and When? Kathleen D. Liu, MD, PhD, MAS June 2011

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1 Dialysis for Acute Renal Failure: Who, What, How, and When? Kathleen D. Liu, MD, PhD, MAS June 2011 Dorre Nicholau MD PhD Clinical Professor Department of Anesthesia and Perioperative Care University of California San Francisco Who? Characteristic N = 1124 Age 60 ± 15 Male gender 70.6% Race White Black Hispanic Other Primary service Medical Surgical Other 74.3% 15.9% 6.9% 2.8% 47.9% 41.2% 11.5% Charlson Comorbidity score 4 ± 3 Mechanical Ventilation 80.6% Sepsis 63% APACHE II score 26 ± 7 Adapted from Palevsky et al, NEJM 2008

2 What modality? Continuous Ambulatory Peritoneal Dialysis (CAPD) Intermittent Hemodialysis (IHD) Slow Low-Efficiency Daily Dialysis (SLED) Continuous Renal Replacement Therapy (CRRT) Continuous Venovenous Hemofiltration (CVVH) Continuous Venovenous Hemodialysis (CVVHD) Continuous Venovenous Hemofiltration with Diafiltration (CVVHDF) Continuous arteriovenous modalities (CAVH, CAVHD, CAVHDF) Is CRRT better than IHD? Potential Advantages of CRRT Hemodynamic stability Increased clearance (compared to qod IHD)?Allows for more aggressive nutritional support Can allow for more aggressive ultrafiltration over time Tight control of volume status in patients with liver failure requiring high volumes of blood products Fewer fluctuations in intracranial pressure

3 Potential Disadvantages of CRRT Labor intensive (nursing/pharmacy) Requires ICU level care More difficult to transport patient Requires continuous anticoagulation For ESRD patients with a graft or fistula, requires placement of a catheter Comparison of IHD and CRRT Vinsonneau et al, Lancet 2006 Multicenter, randomized controlled trial Inclusion criteria: ARF (defined as BUN > or Cr > or oliguria) + need for RRT + multiple organ dysfunction syndrome (LOD score 6) Crossover allowed from CRRT arm to IHD arm if MODS had resolved (LOD score < 5 for 3 days) or after 3 weeks of CRRT

4 Comparison of IHD and CRRT: Criticisms Major temporal change in survival in the IHD group: RR 0.67 per year, 95% CI , p<0.0001) Limited data on dialysis dose Underpowered: initial power calculations based on 45% mortality rate in IHD group, 30% mortality rate in CRRT group

5 How do we decide which modality to use (IHD vs CRRT)? Hemodynamic stability of patient Acid/base status of patient-ongoing acid production, eg severe sepsis Ongoing blood product requirements, eg fulminant hepatic failure (and fewer fluctuations in ICP) Physician/site preference Role of CRRT in management of ICP Davenport, A Sem Dialysis, 2009 Role of CRRT in management of ICP Davenport, A Sem Dialysis, 2009

6 SLED-An alternative to CRRT? Fliser D and Kielstein JT Nat Clin Pract Nephrol, 2006 SLED-An alternative to CRRT? Typically performed over 6-12 hours Can be performed with a conventional dialysis machine A little less labor intensive Requires less training/startup Fliser D and Kielstein JT Nat Clin Pract Nephrol, 2006 How? Processes of care, more pertinent to nephrologists Anticoagulation Membrane characteristics Dose

7 How much is enough? Schiffl et al, NEJM 2002 Single center study of daily vs 3X week HD Were patients underdialyzed? Were patients underdialyzed? Daily 3X week GI bleeding 15% 36% Altered mental status Respiratory failure 38% 69% 35% 59%

8 What new data do we have to guide dose of therapy? Tolwani et al, J Am Soc Nephrol, 2008 Palevsky et al, NEJM 2008 RENAL study, NEJM 2009 Overview of Study Design Intensive Management Strategy Conventional Management Strategy Overview of Study Design Intermittent Hemodialysis (SOFA Cardiovascular Score 0-2) CVVHDF or SLED/EDD (SOFA Cardiovascular Score 3-4)

9 Intensive Management Strategy Intermittent Hemodialysis 6-times per week (target Kt/V of 1.2/treatment) CVVHDF with effluent flow of 35 ml/kg/hr or SLED/EDD 6-times per week (target Kt/V of 1.2/treatment) Conventional Management Strategy Intermittent Hemodialysis 3-times per week (target Kt/V of 1.2/treatment) CVVHDF with effluent flow of 20 ml/kg/hr or SLED/EDD 3-times per week (target Kt/V of 1.2/treatment)

10 60-Day All Cause Mortality Odds Ratio: % CI: P=0.47 Intensive 53.6% Less-Intensive 51.5% 60-Day All Cause Mortality: Subgroup Analysis Management of IHD Intensive Management (N=563) Less-Intensive Management (N=561) Treatments per week (95% CI) 5.4 ( ) 3.0 ( ) Interval between treatments (days, 95% 1.1 ( ) 2.1 ( ) CI) Median treatment length (hours, IQR) 4.0 ( ) 4.0 ( ) Blood flow rate (ml/min) 360±59 360±62 Dialysate flow rate (ml/min) 730± ±135 Net ultrafiltration (L) 1.7± ±1.4 BUN pre-dialysis post-dialysis 45±25 16±12 70±33 25±15 Kt/V urea First treatment Subsequent treatments 1.13± ± ± ±0.33

11 When? Timing of Dialysis Initiation Fischer et al, Surg Gynecol Obstet, 1966 Case series of 235 patients, split by era , dialysis generally initiated when BUN >200 mg/dl (n=120) , dialysis initiated with clinical deterioration or before BUN reached 150 mg/dl (n=115) cohort had lower mortality (57% vs. 74%, 51% vs. 77% if restricted to those on dialysis) Predialysis Urea Nitrogen Mortality Study Year Number Study Design Early Late Early Late Parsons Cohort w/historical controls % 88% Fischer Cohort w/historical controls % 77% Kleinknecht Cohort w/historical controls % 42% Conger Case control % 64% Gettings Retrospective cohort % 80% Bouman Randomized trial % 25% Timing of Dialysis Initiation Demirkilic, J Card Surg, 2005 Cohort study of patients who underwent CABG surgery between March 1992 and September 2001 Group 1: CVVHDF initiated for Cr > 5, K > 5.5 Group 2: CVVHDF initiated for oliguria Group 1 initiated 2.6±1.7 days post-op, Group 2 initiated 0.9±0.33 days post-op

12 Timing of Dialysis Initiation Mortality may be higher with late dialysis Liu et al, CJASN 2006 Patients with dialysis requiring AKI divided at the median BUN (76 mg/dl) Those admitted with an egfr < 30 ml/min were excluded 243 subjects met these criteria Mortality may be higher with late dialysis

13 Mortality may be higher with late dialysis Crude survival rates were higher in those treated with early dialysis despite baseline differences After adjustment for covariates and propensity score, RR of death for those treated with late dialysis was 1.97 (95% CI ) Timing of initiation of dialysis: the ultimate grail How to define early vs late? Subjects in the late group may recover prior to the initiation of dialysis Summary Modality: Data suggests no overall benefit to CRRT compared to IHD, though fewer fluctuations in ICP with CRRT; SLED may be a useful alternative to CRRT Dose: No benefit to intensive therapy, monitor dose of IHD provided Timing: To be determined