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RRT: What Are (Some of) the Unsolved IssuesSean M Bagshaw, MD, MSc
Department of Critical Care Medicine, University of Alberta, Edmonton,
Canada
37th Vicenza Course on AKI & CRRT
Vicenza, Italy
Wednesday, May 29, 2019 ~ 10:00 – 10:20
2019 Disclosures
•Salary: Canada/Alberta government
•Grant: Canada/Alberta government, Baxter
•Consulting: Baxter, CNA Diagnostics, Spectral Medical
•Data Safety Monitoring: CytoPherx
•Co-PI: STARRT-AKI trial
Unsolved Issue # 1: KDIGO Severity Staging To Start RRT
KDIGO CPG for AKI_KI (suppl) 2012
KDIGO AKI Staging As Thresholds for Starting RRT
In patients with AKI RIFLE-F ~ 14% treated with RRT (only 1% with AKI RIFLE-I)1
In patients with AKI KDIGO Stage 3 ~ 66% received RRT (n=272/410; 9% overall)2
In patients with AKI KDIGO Stage 3 ~ 45% received RRT (n=243/540; 13.5% overall)3
1. Hoste E et al Crit Care 2006; 2. Nisula S et al ICM 2013; 3. Hoste E et al ICM 2015
Feature ELAIN AKIKI IDEAL-ICU STARRT-AKI
Country Germany France France Multiple (15+)
No. of Sites 1 31 29 >135
Participants 231 620 488 3,000*
Case-mix Mostly surgical Mostly medical Septic Mixed
Sample calculation (ARR) 18% 15% 10% 6%
Clinician Equipoise No No No Yes
Interventions:
EARLY KDIGO stage 2 KDIGO stage 3 KDIGO stage 3 KDIGO stage 2
DELAYED KDIGO stage 3 Specific criteria* 48 hours Specific criteria*
Primary Endpoint 90-day mortality 60-day mortality 90-day mortality 90-day mortality
DELAYED Death Rate 54.7% 49.7% 54% 37.0%*
Iwashyna et al AJRCCM 2017
Prowle et al KI 2015
Gaudry et al NEJM 2016
•HYPOTHESIS: A strategy of delayed RRT initiation would confer greater survival benefit when compared to a strategy of early RRT initiation among critically ill patients with severe AKI (KDIGO stage 3)
Gaudry et al NEJM 2016
•Death modified by acuity + RRT:•Early: 48.5%•Delayed – NO RRT: 37.1%•Delayed – RRT: 61.8%
Unsolved Issue # 2: Kidney Biomarkers for Starting RRT
Klein SJ et al ICM 2018
ELAIN Trial (n=231) applied plasma NGAL >150 ng/mL as “inclusion” criteria
Plasma NGAL >150 ng/mL as “inclusion” criteria
604 patients screened; only 3 patients excluded for pNGAL <150 ng/mL
Zarbock et al ELAIN JAMA 2016
STARRT-AKI (Pilot) Trial (n=101) applied blood NGAL >400 ng/mL for “inclusion”
While Blood NGAL ≥400 ng/mL as “inclusion” criteria
Median >1,300 ng/mL (lower quartile 774)
Wald et al KI 2015
Prevention of CSA-AKI by Implementing the “KDIGO” Bundle (n=276) applied urine NephroCheck®
Patients undergoing cardiac surgery with [TIMP-2*IGFBP-7] ≥0.3 at 4 hours post-operatively
Application of [TIMP-2*IGFBP-7] provided “predictive enrichment” for risk of AKI
882 screened – 495 (56%) excluded
↑ incidence of post-op AKI
Zarbock et al PrevAKI ICM 2017
Pilot trial of Early vs. Delayed RRT allocated by baseline plasma NGAL (n=40)
Single centre pilot trial of when to start RRT in AKI (Stage 2)
Threshold pNGAL >400 ng/mL to randomize
RRT received by 100% in Early and 40% in Delayed
Srisawat et al J Crit Care 2017
Unsolved Issue # 3: FST For Starting RRT
Chawla LS et al Crit Care 2014
Furosemide Stress Test for Predicting KDIGO AKI Stage 3
FST: furosemide 1-1.5 mg/kg IV bolus
Urine output ≥ 200 mL in 2 hours
Chawla LS et al Crit Care 2014
Furosemide Stress Test for Predicting KDIGO AKI Stage 3
Sensitivity: 87%
Specificity: 84%
AUC: 0.87Chawla LS et al Crit Care 2014
Furosemide Stress Test for KDIGO AKI Stage 3
Rewa O et al J Crit Care 2019
Largely confirmed in prospective observational cohort study
RRT (11%); Sensitivity 70%; Specificity 77%
Furosemide Stress Test as Decision Support for Starting RRT
Lumlertgul et al Crit Care 2018
Furosemide Stress Test To Triage for A Trial of When to Start RRT
Eligible patients received furosemide stress test
FST responsive patients (n=44; 27%) excluded
Fewer FST responsive patients received RRT (n=6; 14%)
Lumlertgul et al Crit Care 2018
Furosemide Stress Test To Triage for A Trial of When to Start RRT
Patients allocated to “standard” RRT ~ 75% received RRT
No difference in mortality (62% vs. 58%) or any other secondary endpoints
Lumlertgul et al Crit Care 2018
Unsolved Issue # 4: Quality of Care in RRT
ADQI 22 - Kashani et al CJASN 2019
ADQI 22 - Kashani et al CJASN 2019
What aspects of your CRRT care do you measure?
Quality CRRT Care
•What is your average filter lifespan?
•What is your average treatment downtime?
•What is your average time to restart after treatment interruption?
•What is your average delivered dose per day?
•What is your average fluid removal per day?
Clark WR et al. Int J Artif Organs 2016
•Seldom routine monitoring/reporting of quality indicators for CRRT
•Paucity of evidence-informed performance standards for CRRT
ADQI 22 - Kashani et al CJASN 2019
MACHINE
CIS
CRRT Quality ManagementDATA INFORMATION
StructureProcess
Outcome
CDSCQI
Performance(Benchmarks)
KNOWLEDGE
Striving for Quality CRRT Care
•Implement and evaluate the feasibility of these QIs into your clinical practice ~ understand your data
•Evaluate the association of these QIs with care processes and patient and health system-related outcomes ~ understand your culture
•Evaluate performance, generate CRRT quality reports ~ generate your own benchmarks
