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John A. Kellum, MD, MCCM Professor of Critical Care Medicine, Medicine, Bioengineering and Clinical & Translational Science Vice Chair for Research Director,

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Presentation on theme: "John A. Kellum, MD, MCCM Professor of Critical Care Medicine, Medicine, Bioengineering and Clinical & Translational Science Vice Chair for Research Director,"— Presentation transcript:

1 John A. Kellum, MD, MCCM Professor of Critical Care Medicine, Medicine, Bioengineering and Clinical & Translational Science Vice Chair for Research Director, Center for Critical Care Nephrology University of Pittsburgh Remote Ischemic Preconditioning – What do we Make of This?

2 Disclosures Consulting: – Fresenius – Gambro – Baxter – Astute Medical – Alere – Spectral – Abbott – AM Pharma – BioAegis – Bard Grant support: – Baxter – Gambro – Astute Medical – Alere – Bard – Grifols Other: – I’m an intensivist

3 AKI No AKI

4 Cell Cycle Arrest In Response To Cell Stress An Alarm Signal Of Impending Cell Damage A protective mechanism?

5 Published on line May 29, 2015

6 Zarbock A et al. JAMA 2015

7

8 1385 Patients AKI (2-3): 5.1% vs 6.1% Euroscore 4.2 (1-2% mortality) No Effect on any primary or secondary endpoints 1612 Patients AKI (2-3): 8.7 % vs 7.6% Euroscore 4.2 (1-2% mortality) No Effect on any primary or secondary endpoints

9 Pre-RIPC Post-RIPC 4 h after CPB 12 h after CPB 24 h after CPB

10 Zarbock A et al. JAMA 2015

11 DAMPs Drive [TIMP-2]  [IGFBP7] and protection from AKI

12 Sham- RIPC RIPC p- value OR/H R * 95% CI MAKE 90, No. [%] 30 (25.0) 17 (14.2) 0.034 0.495 0.256-0.957 Missing Renal Recovery, No. [%] 16 (15.5) 6 (5.8) 0.023 0.333 0.125-0.889 Dialysis dependence, No. [%] 12 (11.5) 4 (3.6) 0.027 0.287 0.089-0.919 Mortality, No. [%], 28-day survival in % (SE) 10 (8.5) 96 (1.7) 11 (9.2) 94 (2.2) 0.835 0.425 1.447 * 0.581-3.603 12 Outcomes

13 Biomarkers: ROC analysis for renal (non)recovery 13 N, all AKI patients; N +, all AKI patients with positive MAKE 90 ; N-, all AKI patients with negative MAKE 90

14 By CKD Status RIPC vs. Sham Adjusted for age, sex and CKD status

15 Conclusions RIPC may be effective in some patients (high-risk?, biomarker +) whereas it appears not to work in others (propofol?). RIPC increases in TIMP-2 and IGFBP7 and protection from subsequent injury --Potential to exploit enate protive mechanism as a therapy? RIPC benefits extend to follow-up Early biomarkers are predictive CKD status might be a factor...

16 www.ccm.pitt.edu

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