Role of diuresis in AKI management W. Van Biesen, Renal Division, Ghent University Hospital.

Declaration of interest: Wim Van Biesen has no declaration of interest for this topic

Injury Markers Functional Markers Disease Available Therapies Myocardial Infarction EKG, ASTCKMB Troponin Ejection Fraction, CO/CI ASA, Heparin, β-blockers, IIB-IIIA, thrombolytics, PTCA, statins, ACE/ARB ALI/ARDS Acute Bilateral Infiltrates on CXR Oxygenation (P/F Ratio) Low Tidal Volume Ventilation Sepsis Tissue Gram Stain, WBC count SIRS Criteria Activated Protein C, EGDT, steroids Nephrology .…. Serum Creatinine, Urine Output, “renal bed rest”

Novel Biomarkers Bonventre Nature Biot 28(5), 2010

Biomarker: Definition (FDA) A characteristic, usually a laboratory test, that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Characteristics of an optimal biomarker: Sensitive to derangement(s) Specific to the disease(s) Predictive of clinical outcomes Robust, i.e. reproducible, inexpensive, simple, and accessible The key points from this session include: A definition of malnutrition as a syndrome that describes inappropriate intake, sometimes in conjunction with disease, that affects body composition, reduces functional capacity, and negatively impacts clinical outcome Despite the negative effects of malnutrition on patients, hospital malnutrition is still prevalent and negatively affects patient outcomes Physician training increases awareness and enhances clinical nutrition practice The Total Nutrition Therapy (TNT) program was developed in response to studies such as those just described. The goal of this program is to increase physician awareness of the continuing problem of malnutrition and the benefits provided by appropriate nutrition therapy, and to provide information and tools to assist physicians in the daily practice of clinical nutrition.

Early Diagnosis of AKI: Hit or Miss? KIM, CysC (0.83) IL-18 (0.75) Fold Increase in Concentration A1M, AAG (0.87) NGAL (0.95) Marker (AUC) Time post-CPB Mishra et al, Lancet 2005 Portilla et al, Kidney Int 2008 Han et al, Kidney Int 2008 Parikh et al, Kidney Int 2006

Impact of using or not using the urinary output criterion in the definition of AKI Vanmassenhove et al, ERA-EDTA Paris, 2012

Diuresis as AKI criterium Macedo et al, KI, 2012

Impact of diuresis on mortality in AKI Ralib et al, Critical Care, 2013

Oliguria as predictor of AKI in SEPSIS Leedahl et al, cJASN, 2014

Oliguria as predictor of AKI in SEPSIS Leedahl et al, cJASN, 2014

Leedahl et al, cJASN, 2014

Conceptual model for development and clinical course of AKI of acute kidney injury. The concept of AKI includes both volume- responsive and volume-unresponsive conditions. These conditions are not mutually exclusive, and a given patient may progress from one to the other. Time runs along the x-axis, and the figure depicts a closing “therapeutic window” as injury evolves and kidney function worsens. Biomarkers of injury and function will begin to manifest as the condition worsens, but traditional markers of function (e.g. urea nitrogen and creatinine) will lag behind hypothetical “sensitive” markers of kidney injury. Mortality increases as kidney function declines. Himmelfarb et al, Clin J Am Soc Nephrol march,2008

Delayed vs timely nephrology consultation in AKI Torres Costa e Silva, PloS, 2013

Diuresis as AKI criterium Potential problems: how to measure? expressed as ml/min/kg: what in overweight patients? what in cachectic patients? what in edematous patients?

Diuresis can only be measured in patients at ICU, as they need an indwelling bladder catheter

Definition of AKI: KDIGO vision

ERBP Position statement on diagnosis of AKI Fliser et al, NDT, 2012

Transient vs intrinsic AKI and tubular injury Based on the creatinine criterion Based on the urinary output criterion Vanmassenhove et al, Istanbul, 2013

Transient vs intrinsic AKI and tubular injury Based on the creatinine criterion Based on the urinary output criterion Vanmassenhove et al, Istanbul, 2013

AKI in the SAPS3 database Joannidis M., Intensive Care Mecicine, 2009

Early intervention Colpaert et al, CCM, 2012

92.8% of alerts induced by low urinary output criterion Early intervention 92.8% of alerts induced by low urinary output criterion Colpaert et al, CCM, 2012

Fluid responsiveness

Furosemide stress test Well rehydrated patients (clinical assumption) AKIN stage I or II IV Furosemide 1mg/kg Hypothesis: Furosemide activity signals normal tubular function

Furosemide stress test Well rehydrated patients (clinical assumption) AKIN stage I or II IV Furosemide 1mg/kg Hypothesis: Furosemide activity signals normal tubular function

Furosemide stress test Well rehydrated patients (clinical assumption) AKIN stage I or II IV Furosemide 1mg/kg Hypothesis: Furosemide activity signals normal tubular function

Kaplan–Meier survival curves grouped by diuretic efficiency (DE) and diuretic dose in the Penn (A) and ESCAPE cohorts (B). Kaplan–Meier survival curves grouped by diuretic efficiency (DE) and diuretic dose in the Penn (A) and ESCAPE cohorts (B). Loop diuretic dose and DE were dichotomized into high and low by the median value in each cohort. Low loop dose was also defined as a loop diuretic dose above or below the median value, which was 280 (interquartile range, 120–600) mg in the Penn cohort and 240 (interquartile range, 120–400) mg in 24 h in the ESCAPE cohort. Jeffrey M. Testani et al. Circ Heart Fail. 2014;7:261-270 Copyright © American Heart Association, Inc. All rights reserved.

Impact on outcome of increased awareness of AKI Selby et al, Current Opin Nephrol Hypertension 2013

Conclusion Diuresis and urinary output is an important biomarker for the prevention, diagnosis and management of AKI Its implementation is a matter of WILLING rather than of possibility