Biomarkers to define AKI Michael Zappitelli, MD, MSc.

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Presentation transcript:

Biomarkers to define AKI Michael Zappitelli, MD, MSc

What are these new biomarkers? KIM-1 NGAL IL-18 TIMP2/IGFBP GST CysC Metabolomics

Objectives Focus on utility and not actual biomarkers: e.g. PICU, Cardiac Maximizing biomarkers: Renal angina index Future

1 year old for TOF repair Serum creatinine (umol/L) 0-6 hrs 45 2 days 100 before surgery 40 surgery low BP 5 days peritoneal dialysis

What happened here … Could this have been prevented? Could novel biomarkers help?

Post-operative AKI prediction: early SCr rise IL-18 uNGAL pNGAL

Post-operative AKI prediction: NGAL & IL-18: AUC Adults Children 5 th Quintile cutoffs Sensitivity/Specificity: IL-18: 60 pg/ml 54% /82% 364 pg/ml 38% / 84% uNGAL 102 ng/ml 46% /81% 72 ng/ml 42% / 85% pNGAL 293 ng/ml 50% / 82% 261 ng/ml 27% / 81%

Biomarker combinations Single: 0.56 – 0.76

1 year old for TOF repair Serum creatinine (umol/L) 0-6 hrs 45 2 days 100 before surgery 40 surgery low BP 5 days peritoneal dialysis

12 year old girl with sepsis PICU SCr rise ?truly AKI Will she need dialysis? Will she progress? Nephrotoxins Low BP

NGAL AUC 0.78

Adding biomarker to other data

SCr has risen: should I worry? Outcome: AKI>48 hrs AUC=0.80 Replication cohort, unpublished: Day AKI first appears: NGAL: AUC 0.75 IL-18: AUC 0.80 LFABP: AUC 0.80

CAN WE DO BETTER? RENAL ANGINA INDEX

Focus is on QUICK and SIMPLE assessment Intent is to have an index / threshold risk with HIGH NPV No Renal Angina: HIGHLY likely NOT to develop AKI Do NOT study biomarker performance Do NOT use biomarkers to predict AKI (future)

New: Proposed RA index Basu et al, KI 2014

Take a step back: summarize  Biomarkers: Several candidates – which work best in what patients. Early diagnosis Short term prognosis ?Long-term prognosis Biomarker combinations +/- clinical risk factors likely best Will allow for clinical trials  Taking Focus Study:  Using biomarkers and fluid overload severity to make decisions on fluid management and CRRT start.

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THANK YOU pCRRT conference organizers Montreal Children’s Hospital AKI research team Collaborators/mentors: Stuart Goldstein, Prasad Devarajan, Chirag Parikh The Kidney Injury During Membrane Oxygenation group