1. AKI ITSELF EPIDEMIOLOGY Michael Zappitelli, MD, MSc Montreal Children's Hospital McGill University Health Centre

2. Epidemiology: Distribution and patterns of  Health-events  Health-characteristics  Their causes, determinants or influences in well- defined populations AKI Who, What, When, Where, Why and How?

3. Past: Pediatric AKI studies Mostly studies of RRT requirement: rare Pediatric acute RRT is not easy! SmallSmallRetrospectiveRetrospective Lack of understanding of severity spectrum Poor outcome Studies on acute RRT technique Pediatric RRT refinement Experience description

4. Past: Pediatric AKI studies Pre-2004 Pre-2004:  Descriptions of specific diagnoses - HUS Malaria Glomerulonephritis Bee stings!!

5. Williams et al, Arch Ped Adolesc Med, 2002 Changes with Era's HUS: >25% to ~15% Heme-Onc: 8 to ~18% Sepsis:No change (~1/5) HUS: >25% to ~15% Heme-Onc: 8 to ~18% Sepsis:No change (~1/5)

6. Changes with Era's Williams et al, Arch Ped Adolesc Med, 2002 Moghal et al, Clin Nephrol 1998 UK, 1984-1991  52% of AKI referred cases either HUS or “primary renal disease”  Most patients requiring RRT: “primary renal disease”

7. DEFINITIONS Pediatric AKI – around the world!

8. AKI or AKI recognition may be increasing Vachvanichsanong et al, Pediatrics, 2006 THAILAND

9. Overview Epidemiology Today Studies using recent definitions Incidence Characteristics, patterns Outcomes, mortality Studies reporting RRT need Incidence Characteristics Mortality Highlighting: Different regions Diagnostic populations

10. AKI- using definitions X Goodbye X

11. Incidence: PICU full cohort studies Schneider et al, Ped Crit Care, 2010 USAN=3396 No severe CKD CreatUSAN=3396 Creat Kayaz et al, Acta Pediatr, 2012 Turkey N=189 No severe CKD Creat Turkey N=189 No severe CKD Creat

12. Incidence: PICU partial cohort studies Ackan-Arikan, Ped Crit Care, 2007 Plotz et al, Intens Care Med, 2008 Krishnamoorthy, et al, Ind J Ped, 2012 USAN=150 Vent and/or Vaso, Foley Creat + Urine USAN=150 Vent and/or Vaso, Foley Creat + Urine Netherlands N=189 Vent ≥4 days Creat + Urine Netherlands N=189 Vent ≥4 days Creat + Urine South India N=215 >48 hours Creat + Urine South India N=215 >48 hours Creat + Urine North India N=486 >24 hours, NO severe Admx AKI Creat North India N=486 >24 hours, NO severe Admx AKI Creat Mehta, et al, Ind Ped, 2012 CanadaN=2106 ≥12 hours CreatCanadaN=2106 Creat Alkandari et al, Crit Care, 2011

13. Incidence: Cardiac 4 US studies (1594) Manrique, Ped Anesth, 2009 Li, Crit Care Med, 2011 Aydin, Ann Thorac Surg, 2012 Blinder, J Thor Card Surg, 2012 4 US studies (1594) Manrique, Ped Anesth, 2009 Li, Crit Care Med, 2011 Aydin, Ann Thorac Surg, 2012 Blinder, J Thor Card Surg, 2012 1 Indian study (124) Sethi, Clin Exp Nephrol, 2011 1 Indian study (124) Sethi, Clin Exp Nephrol, 2011 2 Canadian studies (646) Morgan, j Ped, 2012 Zappitelli, KI, 2009 2 Canadian studies (646) Morgan, j Ped, 2012 Zappitelli, KI, 2009 1 Hungarian study (1510) Toth, Card Anethes, 2012 1 Hungarian study (1510) Toth, Card Anethes, 2012

14. Incidence: Nephrotoxins Smyth et al, Thorax, 2008 Case-control study, CF 24 AKI (UK CF Database) IV Aminoglycoside independent RF Aminoglycosides ≥5 days N=557 Zappitelli et al, NDT, 2011 McKamy et al, J Peds, 2012 ? independent of ICU/other drugs? Vancomycin ≥2 days N=167 Increasing numbers (≥3) of NTM used Increases risk for AKI in non-ICU children Moffett & Goldstein, CJASN, 2011 Increasing numbers (≥3) of NTM used Increases risk for AKI in non-ICU children Moffett & Goldstein, CJASN, 2011

15. Incidence: Stem cell transplant & other cancers  Most commonly expressed as SCr doubling  Generally determined 30-100 days post  Range from 5 to 40%!  Many nephrotoxins, critical illness, sepsis  Better understanding of AKI spectrum needed

16. RRT-requiring AKI X Goodbye X

17. ~1% ~1-3% ~4% ~6% 5-6% 1-2% PD>> others Cardiac surgery: 0 to 31%! Incidence of D-AKI

18. 50-60% 40-45% 36% 25-50% 42-67% 52-77% 33-65% 40% 50-60% 64% 11% RRT-AKI Mortality high everywhere (almost!)

19. Characteristics, patterns  AKI due to other causes >>> primary renal disease  Developing countries: More importance of primary renal disease, Malaria, HUS However, now secondary causes emerging  “TOP HITS” around room: “ATN” “Hypovolemia” Sepsis Nephrotoxic medication – almost always significant when looked at!! Heme-Onc Cardiac surgery  Majority have multiple organ dysfunction

20. Characteristics, patterns

21. Confirmed in several other larger epidemiologic cohort studies Distribution of the day of admission that subjects reached pRIFLEmax (n=123) and pRIFLE F stratum (n=31). Characteristics, patterns AKI OCCURS EARLY

22. Outcome associations  In repeated studies last 5 years:  AKI independently associated with PICU mortality Length of stay Duration of mechanical ventilation  Graded response: Stage 1 worse than 2 worse than 3  A few studies: associated with higher costs Difficult to REALLY know if independent of illness severity

23. Importance of all these studies Paradigm changed  Only severe AKI, requiring RRT is of serious significance.  AKI is a marker of disease severity.  People die WITH AKI, not BECAUSE of AKI.  AKI is a spectrum of disease: worse AKI = more significance  AKI is more likely and worse, with increasing illness severity.  AKI itself may be an independent contributor to poor outcome. PASTCURRENT