1. The Unrecognized Epidemic of Nephrotoxin-associated Acute Kidney Injury Eric Kirkendall, MD, MBI Medical Director of Clinical Decision Support Hospital Medicine, Biomedical Informatics, James M. Anderson Center for Health Systems Excellence

2. We have no other financial relationships to disclose or Conflicts of Interest (COIs) to resolve. This project was funded by grant from the Agency for Healthcare Research and Quality (AHRQ)

3. Background Nephrotoxic medication (NTMx)-associated Acute Kidney Injury (AKI) is one of the most common causes of AKI in hospitalized children. Most Common ARF Causes  ATN-Dehydration (21%)  Nephrotoxic drugs (16%)  Sepsis (11%)  Unknown (14%)  Primary Renal Disease (7%) Hui-Stickle et al, 2005; Pediatric ARF Epidemiology in a Tertiary Care Center from 1999 to 2001

4. Background Recent studies demonstrate that NTMx-AKI occurs at higher than previously recognized rates. Patients receiving IV AG > 5 days AKI by pRIFLE Primary renal diagnoses excluded One year of study (n = 557 children, 95% > 3 months of age) AKI rates by pRIFLE = 33% Zappitelli et al, 2011; Acute Kidney Injury in non-critically ill children treated with aminoglycoside antibiotics in a tertiary care center

5. Background Recent studies demonstrate that NTMx-AKI occurs at higher than previously recognized rates. 86% of patients 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 Moffett et al, 2011; Acute Kidney Injury and Increasing Nephrotoxic-Medication Exposure in Noncritically-ill Children

6. Background A portion of NTMx-AKI goes unnoticed due to lack of kidney function surveillance in susceptible children. SCr measured at least q4 days only 50% of the time in patients on AGs for ≥5 days Zappitelli, 2011; Acute Kidney Injury in non-critically ill children treated with aminoglycoside antibiotics in a tertiary care center

7. Background Nephrotoxic medication (NTMx)-associated Acute Kidney Injury (AKI) is one of the most common causes of AKI in hospitalized children. Recent studies demonstrate that NTMx-AKI occurs at higher than previously recognized rates. A portion of NTMx-AKI goes unnoticed due to lack of kidney function surveillance in susceptible children.

8. Background Nephrotoxic medication (NTMx)-associated Acute Kidney Injury (AKI) is one of the most common causes of AKI in hospitalized children. Recent studies demonstrate that NTMx-AKI occurs at higher than previously recognized rates. A portion of NTMx-AKI goes unnoticed due to lack of kidney function surveillance in susceptible children. Hypothesis: More reliable surveillance of NTMx exposure and injury would demonstrate that rates of AKI are high, that… an epidemic exists. Hypothesis: More reliable surveillance of NTMx exposure and injury would demonstrate that rates of AKI are high, that… an epidemic exists.

9. Objectives of the Study Quantify the rate of High NTMx exposure and NTMx-AKI in the non-critical care population. Determine if this EHR-based AKI screening intervention led to changes in AKI prevalence, or duration (intensity)

10. Methods Find NTMx-exposed patients prospectively Reliably monitor serum creatinine (SCr) for evidence of injury Measure exposure and injury rates, changes over time Use electronic triggers within the electronic health record (EHR) and automated reports to make the process more efficient and complete

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. Injury (AKI) Criteria* –p (pediatric) –R = Risk, at 150% of baseline creatinine value (SCr) –I = Injured, at 200% of baseline SCr –F = Failure, >= 300% of baseline SCr –L = Loss, persistent failure > 4 weeks –E = End-Stage Renal Disease, > 3 months pRIFLE criteria *KDIGO AKI guideline criteria

13. Injury (AKI) Criteria* pRIFLE criteria or >= 0.3mg/dL increase in SCr in 48 hours

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

16. Meets High NTMx Exposure Criteria

17. AKI Surveillance Algorithm Injury surveillance loop

18. AKI Surveillance Algorithm Exposure surveillance loop

19. AKI Surveillance Algorithm End Surveillance

20. Daily email report with links…

22. Demographics

23. Last 3 SCr

24. Demographics Last 3 SCr NTMx’s

26. Inclusion Flowchart

27. Distribution of Exposure and Injury Services High NTMx Exposure Cases n = 945 Developed AKIGender Count% of cohort No n = 655 Yes n = 290 % Female n = 459 Male n = 486 Bone Marrow Transplant26327.8314212146.01108155 Liver Transplant13113.86844735.888150 Oncology10511.11683735.244758 Pulmonary778.15542329.873245 Cystic Fibrosis717.516568.454328 General Pediatrics646.776046.253529 GI Surgery, Trauma394.13281128.211920 Orthopedics303.1725516.67219 Cardiology272.8618933.331314 Urology272.862527.411215 2.9% of all admitted patients were High-NTMx exposed AKI occurred in 25% of highly exposed unique patients; 31% of all exposed admissions developed AKI

28. Distribution of Exposure and Injury Services High NTMx Exposure Cases n = 945 Developed AKIGender Count% of cohort No n = 655 Yes n = 290 % Female n = 459 Male n = 486 Bone Marrow Transplant26327.8314212146.01108155 Liver Transplant13113.86844735.888150 Oncology10511.11683735.244758 Pulmonary778.15542329.873245 Cystic Fibrosis717.516568.454328 General Pediatrics646.776046.253529 GI Surgery, Trauma394.13281128.211920 Orthopedics303.1725516.67219 Cardiology272.8618933.331314 Urology272.862527.411215 2.9% of all admitted patients were High-NTMx exposed AKI occurred in 25% of highly exposed unique patients; 31% of all exposed admissions developed AKI

31. total number of new High NTMx exposure patients in a given week total number of non ICU days in a given week Rate of Exposure * 1000 days Rate of exposure=

32. total number of new NTMx-AKI patients in a given week total number of non ICU days in a given week * 1000 days Rate of AKI=

33. Proportion of high NTMx exposure patients who develop AKI Avg: 25.5 total number of new High NTMx exposure patients in a given week total number of new AKI patients in a given week Percent =

34. Desired change total number of AKI days in a given week total number of High NTMx-exposed days in a given week * 100 days AKI Intensity= AKI Intensity

35. Desired change total number of AKI days in a given week total number of High NTMx-exposed days in a given week * 100 AKI Intensity= AKI Intensity Potential to save ~900 AKI days per year!! $$$

36. Summary Table MetricData TrendNotes High NTMx exposure rate  Likely due to automated reports picking up more NTMx AKI rate ,, ? Census fluctuations, education % High NTMx-exposed patients who developed AKI no change Remained stable, ? decreased variation AKI Intensity  Decreased 40%, potential savings of ~900 AKI days/year at CCHMC

37. Limitations External validity; data from only one site –Future work to spread project to other large pediatric institutions AKI attribution to NTMx exposure –Possible that other etiologies of AKI were present, but patients had to be susceptible (exposed to NTMx) to be included in our study cohort

38. Take Home Points A reliable prediction and detection system detected high numbers of NTMx-exposed and NTMx-AKI patients NTMx-AKI is a relatively common phenomenon in hospitalized non-ICU children Sub-populations have been identified as targets for future interventions Large potential for preventing AKI and saving healthcare dollars

39. Many thanks to the “Nephro Ninjas” and for allowing us to present our data today… Cynthia Barclay, PharmD, & all the clinical pharmacists!! Joshua Schaffzin, MD, PhD Marshall Ashby, MBA, MHSM Stuart Goldstein, MD

41. Next Steps Still tweaking queries Interventions planned for target subsets of patient population (Pulmonary, BMT, GI) Spread to other institutions Several manuscripts on their way!!

42. Challenges Complexity: novel definitions/metrics, surveillance algorithms, trigger queries, inclusion/exclusion criteria Competition for resources Rapid-cycle QI methodologies vs static programming Multidisciplinary approach: many, many people involved