1. Drug Induced AKI and NINJA
Stuart L. Goldstein, MD
Clark D. West Endowed Chair
Professor of Pediatrics
University of Cincinnati College of Medicine
Director, Center for Acute Care Nephrology
Medical Director, Pheresis Service
Cincinnati Children’s Hospital Medical Center

2. Disclosures
Baxter/Gambro Renal Products
Grant Support/Expert Panel/Consultant
Luitpold
Consultant for a clinical trial
Medtronic
Consultant
AM Pharma
Otsuka
Steering committee for trial
Astute Medical Inc
Bioporto
Reata Pharmaceuticals
DSMB Member
MediBeacon, Inc
Director of Clinical Development
The topic of this presentation is not relevant to my work with any industry sponsor

3. Felis Catus Bunchmanius?

5. High Level Rationale for NINJA
One of the most common causes of AKI in non-critically ill hospitalized children
A portion of NTMx-AKI goes unnoticed due to lack of systematic kidney function surveillance in exposed children
Multiple studies show SCr measured at least every four days only 50% of the time in children receiving multiple NTMx
NTMx-AKI may be a potentially modifiable adverse safety event if
At-risk patients are identified
Systematic SCr monitoring is instituted reliably in at-risk patients
AKI is avoided and/or mitigated by reducing unnecessary NTMx exposure

6. Motivation or Why did I get interested in NTMx-AKI?
Frequent consults for patients receiving multiple NTMx with AKI
Tired of writing “AKI secondary to NTMx, we will follow with you”, in the chart
Early NTMx-AKI epidemiological research to get an accurate AKI rate was difficult
SCr surveillance inconsistent and differed between services
Started as an economic exercise

7. NINJA Vision Statement
Children should only get the nephrotoxic medications they need for the duration they need them

8. Patients receiving IV AG > 5 days Primary renal diagnoses excluded
One year of study
557 children
95% > 3 months of age
AKI occurred in 19-33% of patients
SCr measured at least q4 days only 50% of the time

9. 350 non-critically ill children with AKI by pRIFLE
350 matched children without AKI
38 potential NTMx
Compared NTMx exposure rate between AKI vs. non- AKI patients
86% exposed to at least 1 NTMx
Patients with AKI had 1.7 OR for exposure to a NTMx
PPV for AKI doubles for patient with 3+ NTMx

10. Objectives of NINJA
Develop and EHR-based AKI screening intervention to assess changes in AKI prevalence, or duration (intensity)
RELIABLY QUANTIFY the rate of High NTMx exposure and NTMx-AKI in the non-critical care population.

11. High NTMx-exposure Criteria
Patient receiving 3 or more nephrotoxic medications (NTMx) concomitantly* or On an aminoglycoside for 3 or more days
*IV radiology contrast, amphotericin, or cidofovir in previous week is counted for the week following administration

12. Nephrotoxic Medication List

13. Outcome Measures

14. The Process
Pharmacists create/receive daily reports, verify & validate
Provide SCr screening suggestions if necessary
Data Analyst compiles registry from Pharmacist reports…
…and generate metrics, run charts
Share with AKI team, leadership, other stakeholders

15. AKI Surveillance Algorithm
Injury surveillance loop
Meets High NTMx Exposure Criteria
Update slide
Exposure surveillance loop
End Surveillance

18. 99% compliance with daily SCr monitoring in all
Inclusion Flowchart
99% compliance with daily SCr monitoring in all
high NTMx-exposed patients
Data span June 2, 2011 – June 4, 2012

19. EHR Trigger reports improve detection of NTMx exposure in Year 1

21. than CLBSI rates at CCHMC
Initial AKI prevalence rates 10-fold higher than CAUTI rates and 3-fold higher
than CLBSI rates at CCHMC

22. AKI intensity decreases in Year 1 of the project by 42%
Associated with 908 AKI days avoided in one year

27. Adverse Events Avoided

28. Review of electronic health record
First 100 patients with NTMx-AKI assessed at > 6 months after AKI episode
Review of electronic health record
Nephrology Clinic visit (y/n)
Serum creatinine
Urine for protein and creatinine
Cystatin C
GFR estimation from serum creatinine and/or CysC

29. Before AKI
Hospital DC
6 months
post-AKI
eGFR (ml/min/1.73m2)
<90
0/100
22/92
(5<60)
18/77
(2< 60)
90-150
100/100
70/92
50/77
>150
0/92
9/77
Cystatin C eGFR (ml/min/1.73m2)
N/A
80+23
Urine protein/creat >0.2
0/15
27/34

30. Dissemination of NINJA
Disseminate NINJA implementation at nine pediatric hospitals
Measure the impact of NINJA on NTMx-AKI in participating hospitals
Assess the association between context measures, including network participation, and reduction in NTMx-AKI by individual hospitals across the network

35. Vision for NINJA
Develop reliable AKI detection and mitigation across the collaborative
Once the clinical NINJA engine is in place, this reliable NTMx-AKI phenotype will allow for:
Disease specific epidemiology and AKI reduction strategies
Development of translational research initiatives
Pharmacogenomics
AKI biomarker validation
Personalized AKI detection and reduction strategies

36. Stuart,
When should I add Hopkins, Wisconsin, Mott to this slide?

37. Acknowledgements Eric Kirkendall, MD, MBI Stephen Muething, MD
Theresa Mottes, RN, BSN, CNP-PAC
Jason Olivea
Devesh Dahale
Cynthia Barclay, PharmD