Managing the Frail Kidney with CRRT

Raghavan Murugan, MD, MS, FRCP, FCCMAssociate Professor of Critical Care Medicine &Clinical and Translational ScienceCenter for Critical Care NephrologyUniversity of Pittsburgh School of Medicine

Chief, Critical Care MedicineMagee Womens Hospital of UPMC

•National Institute of Health (NIDDK)

• La Jolla, Inc.

•AM Pharma, Inc.

•Bioporto, Inc.

•Beckman Coulter, Inc.

Disclosure

•Maintain fluid and electrolyte homeostasis

•Preserve residual renal function

• Facilitate patient and renal recovery

Goals of Renal Support with CRRT

Epidemiology and Outcomes of Fluid Overload

Author Year PopulationDefinition of

FOPrevalence of FO Mortality

Balakumar et. al. 2016 ICU patients > 5% 45% 40%

Mitchell et. al. 2015 Sepsis >10% 86% -

Vaara et. al. 2012 ICU patients >10% 27% 32%

Bellomo et. al. 2011 AKI/RRT Positive FB 48% 57%

Fullop et. al. 2010 CRRT >10% 47% 50%

Lovell et. al. 1990 Surgical ICU >10% 40% 19%

Positive Fluid Balance is Associated with 1 Yr Mortality

Adjusted Hazard Ratio Range* P Value

Positive vs Even FB: 1.3-1.71 < 0.001Balakumar V et. al. Crit Care Med 2017;45:e749–e757.

Fluid Overload affects all Organ Systems

Prowle J, et al. Nat Rev Nephrol 2010

Fluid Overload at ICU Discharge is Associated With Impaired Functional Outcomes

Inability to ambulate

Discharge to a healthcare facility

Mitchell KH et al., AJRCCM 2015

Renal Replacement Therapy is associated with Lower Mortality in Patients with Positive Fluid Balance

AHR range for positive FB*RRT, 0.43-0.89, P<0.001

*Adjusted for Age, Sex, Race, BMI, Multiple comorbidities, Malignancy, Heart disease, Heart failure, Liver disease and associated

complications, Liver transplant, Baseline creatinine, Liver Transplant, Surgery, AKI, Oliguria, Apache 3 score, sepsis, hypotensive

index, use of vasopressors, mechanical ventilation

Balakumar V et. al. Crit Care Med 2017;45:e749–e757.

Volume Control with CRRT

Bouchard et al. Kidney International 2009

Optimal “dosing” for solute control

Kellum & Ronco Nat Rev Nephrol. 2010 Apr;6(4):191-2

• Uncertainly exists over “optimal rate” of net ultrafiltration

• Practice guidelines suggest net ultrafiltration should individualized• how best to “individualize” is unclear

• Slower rate of net ultrafiltration increases exposure to tissue edema leading to organ dysfunction and mortality

• Rapid rate of net ultrafiltration is associated with cardiovascular stress, hypotension and organ ischemia

• Both organ edema and ischemia are associated with increased mortality

Rate of Net Ultrafiltration and Outcomes

Silversides et al. Critical Care 2014, 18:624Prowle, J.R. et al; Nat Rev Neprol 2010McIntyre CW et. al. CJASN 2008

Longer Treatment Time and Slower Ultrafiltration Are Associated with Reduced Mortality

Saran et. al. Kidney International (2006) 69, 1222–1228.

Rapid Net Ultrafiltration Rate and Is Associated with Mortality in ESRD Patients

Flythe JE al., Kidney International 2011

Intradialytic Hypotension and Mortality

Silversides et al. Critical Care 2014, 18:624

Prescription Strategies to Minimize Hypotension

Rosner MH, et al., BJA 2014

Net Ultrafiltration Rate (mL/kg/hr) = net volume removed (mL)weight (kg) x duration of KRT (days)

Net Ultrafiltration Rate and Mortality in Critically Ill

High: >25ml/kg/day (n=475)

Moderate: ≤25->20ml/kg/day (n=166)

Low: ≤20ml/kg/day(n=434)

• Single center study (N=1075)

• All patients with >5% fluid balance and received renal replacement therapy (RRT)

• Included both CRRT and IHD based on first modality

• Primary exposure variable was UFNET in mL/kg/day

• Outcome: 1 year mortality Murugan R et. al. Critical Care 2018

Net Ultrafiltration and 1-Year Mortality

Murugan R et. al. Critical Care 2018

Sensitivity Analysis

Characteristic Net Ultrafiltration

Intensity Adjusted Odds Ratio

(95%CI)f P

value

Sensitivity analysis

UFNET up to 72 hours after RRT initiationa

High vs low 0.56 (0.35 – 0.88) 0.013

Moderate vs low 1.10 (0.58 – 2.11) 0.76

Alternative UFNET thresholdb High vs low 0.63 (0.41 – 0.97) 0.038

Moderate vs low 0.91 (0.53 – 1.58) 0.74

Alternative UFNET thresholdc High vs low 0.58 (0.34 – 0.99) 0.044

Moderate vs low 0.66 (0.43 – 1.01) 0.053

Subgroup analysis UFNET among the subgroup of

patients with cumulative FB >

20% before RRTd

High vs low 0.52 (0.26 – 1.05) 0.07

Moderate vs low 0.74 (0.29 – 1.84) 0.51

Alternative UFNET threshold among the subgroup of patients

who only received CRRTe

High vs low 0.41 (0.24 – 0.71) 0.0013

Moderate vs low 0.68 (0.39 – 1.18) 0.17

Murugan R et. al. Critical Care 2018

• Internet-assisted survey of• Intensivists,• Nephrologists• Nurse practitioners• ICU nurse• Dialysis nurse

• 80 countries

• 14 International societies

• Endorsed by • SCCM• ESICM• CSCCM• JSCCM

Multinational Survey of Net Ultrafiltration Prescription and Practice

Geospatial Distribution of Survey Respondents

N=1,569 respondents

Net Ultrafiltration Rates by Country

• Fluid overload is associated with increased morbidity and mortality

• Initiating CRRT in a patient with fluid overload is associated with lower risk of death

•Preliminary evidence suggests that there is an association with rate of net ultrafiltration and mortality• There is wide variation in net ultrafiltration rates across the world• Clinical trials are required to examine association between net ultrafiltration rate and

mortality

•Rapid net ultrafiltration might increase mortality by hemodynamic stress

Conclusions

• Vikram Balakumar, MD

• Samantha Kerti, MS

• Joyce Chang, PhD

• Priyanka, Priyanka, MPH

• Ali Smith, MS

• John Kellum, MD

• Paul Palevsky, MD

• Gilles Clermont, MD

• Rinaldo Bellomo, MD

• Claudio Ronco

Acknowledgments

Visit us at http://www.ccm.pitt.edu/center-critical-care-nephrology

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muruganr@upmc.edu

@RagiCCM