What did we aim to learn from the FINNAKI -study

Transcription

1 What did we aim to learn from the FINNAKI -study Maija Kaukonen, MD, PhD, EDIC Specialist in anesthesiology and intensive care Specialist in clinical phramacology Intensive Care Units, Division of Anaesthesia and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland

2 Acute Kidney Injury -AKI Definition and classification of AKI: RIFLE 2004, AKIN 2007, KDIGO 2012 These criteria are based in measurements of serum creatinine or urine output

3 RIFLE & AKIN & KDIGO mg/dl = 26 umol/l 0.5 mg/dl = 44 umol/l 4 mg/dl = 354 umol/l KDIGO 2012

4 AKIN vs. RIFLE Joannidis et al. ICM 2009

5 AKIN vs. RIFLE RIFLE: 9% of patients unrecognised that were recognised by AKIN 90% of thse were AKIN Stage 1 patients AKIN: 26.9% of patients unrecognised that were recognised by RIFLE 30% of these were RIFLE I 18% of these were RIFLE F Joannidis et al. ICM 2009

6 AKI progression

7 Creatinine as marker for AKI Limitations of creatinine Slow and lateincrease in AKI Largeinterindividualvariation (age, musclemass etc.) Is affectedbyfluidbalance (dehydration&volumeoverload) Is notspecific for tubularinjury Increasesonlyaftersignificantloss of GFR Is a poorprognosticmarker

8 AKI biomarkers Bagshaw SM. Bellomo R. Et al. Canadian Journal of Anaesthesia;

9 AKI biomarkers Devarajan, P. Nephrology 2010

10 Subclinical AKI Haase, Devarajan et al. J Am Coll Cardiol Apr 26;57(17):

11 Population-basedincidence of AKI Population-based incidence of hospital treated AKI: Ali, 2007: 2147 / million / year (RIFLE, retrospective, one region, Scotland, population of 523,390) Population-based incidence of ICU treated AKI: Cartin-Ceba, 2011: 2900 / million / year (RIFLE, retrospective, one county area USA, population of 124,277)

12 AKI incidence ICU patients AKI % Cruz 2007 (2164) 10.8 Thakar 2009 ( ) 22.0 Joannidis 2009 (16 784) 28.5 Ostermann 2007 (41 972) 35.8 Bagshaw 2008 ( ) 37.1 Hoste 2006 (5383) 67.2

13 AKI long-term prognosis Wald, R., R. R. Quinn, et al. JAMA 2009.

14 AKI mortality AKI Hospital Mortality % Stage 3 / RIFLE F Hospital Mortality % AKI Long-term mortality Hoste 2006 (5383) Ostermann 2007 (41 972) Bagshaw 2008 ( ) Joannidis 2009 (16 784)

15 AKI genetics AngiotensinConvertingenzyme I/D geneticpolymorphism 180 ICU patients, association with AKI (RIFLE criteria) Hypoxia-inducedfactor patientswith AKI Association withdiseaseseverity and outcome TNF alpha and IL 10 genepromotorpolymorphisms 61 patientswithacuterenalfailurerequiringhemodialysis Association withincreasedmortality du Cheyron D, Fradin S, Ramakers M, et al. Angiotensinconvertingenzyme I/D geneticpolymorphism: Itsimpact on renalfunction in criticallyillpatients. CritCareMed 2008;36: Kolyada AY, Tighiouart H et al. A geneticvariant of hypoxia-induced factor-1a is associatedwithadverseoutcomes in acutekidneyinjury. KidneyInt 2009; 75: Jaber BL, RaoMadhumathi, Guo D et al. Cytokinegenepromoterpolymorphisms and mortality in acuterenalfailure. Cytokine 2004; 25:

16 FINNAKI AKI study RRT substudy Finnsepsis II Genetic substudy Cardiac surgery substudy

17 Study population FINNAKI FINNSEPSIS II RRT substudy Cardiac surgery substudy Genetic study RRT outside ICU

18 Patientflow ICU admission Excluded patients Cardiac surgery substudy AKI study FINNSEPSIS II Genetic substudy RRT -substudy RRT treated AKI patients outside ICU

19 FINNAKI The aims of the study Incidence of AKI in ICU and in Finnish population Risk factors for AKI Outcome of AKI Renal recovery Mortality (90 day, 6 month, 12 month, 5 year) Quality of life after AKI Cost-utility of the treatment of AKI The mechanism of AKI; apoptosis/endothelial damage and inflammatory markers (eg. P-DNA, MMP-2, MMP-8, MMP-9, IL-6, TIMP-1, TIMP-2, PINP, PIIINP ja ICTP, caspases) New biomarkers of AKI Predictive value for AKI, RRT treatment and mortality (e.g. P-/U-NGAL, U-NAG, U-KIM-1, U-IL-18)

20 RRT substudy Incidence of RRT treatment in FinnishICUs Riskfactors for RRT treatment in ICU Description of RRT Outcomeof AKI Incidence of RRT treated AKI outside ICUs All AKI patientsincludedifnephrologicalconsultation is asked for the need of renalreplacementtherapy Description of RRT Outcome of AKI

21 FINNSEPSIS II -substudy Incidence of septic AKI in ICU and in Finnishpopulation Riskfactors for septic AKI Outcomeof septic AKI Renalrecovery Mortality (90 day, 6 month, 12 month, 5 year) Quality of life afterseptic AKI Cost-utility of the treatment of septic AKI Biomarkers of septic AKI

22 Cardiac surgery substudy Incidence and interrelation of cardiac injury and AKI measured with new cardiac biomarkers Correlation of acute kidney injury biomarkers and cardiac injury biomarkers with risk scoring (Euroscore, Syntax), morbidity and mortality

23 FINNAKI Inclusion Exclusion Emergency admission Elective admission >24 h Under 18 years Elective admission < 24h On chronic RRT Organ donor Initiation of chronic RRT Declined / No consent Nonresident Previously in study with RRT Over 5 days in study in another ICU Intermediate care

24 Collection of data Demographics Screening of riskfactors for AKI for 5 Screening of severesepsis/ septicshock for 5 days DetailledRRT data Hemodynamic data as 5 min median values for the whole ICU stay (electronicalcollection) Laboratoryvalues and vasoactivetreatment for the whole ICU stay (electronicalcollection) Laboratorysampling: Bloodand urine sampling0 h, 12 h, 24 h, 36 h, 48 h, day 3, day 5

25 FINNAKI execution Studyprotocolpreparation in 2010 Pilotstudy Patientrecruitment Extension for severesepsispatients and RRT patients to Cardiacsurgerysubstudyrecuritmentup to

26 FINNAKI 5853 ICU admissionsduringpatientrecruitmentperiod 2901 ICU patientsincluded infinnaki 2825 patients in geneticsubstudy 918 patients in FINNSEPSIS II 367 patients in RRT substudy 296 patients in ICUs 71 patientstreated outside ICUswith RRT for AKI Cardiacsurgerysubstudyrecruitment is ongoing (400 patientsrecruited28.05.)

27 FINNAKI near future Population basedincidence of AKI RRT -substudy FINNSEPSIS II

28 FINNAKI - biomarkers Earlierdiagnosis of AKI in future Validationof new biomarkers in unselected ICU patientcohort NGAL, IL-18, KIM1 Biomarkerpanelfor diagnosing AKI in unselected ICU patients? Progress and resolutionof AKI in light of new biomarkers? Biomarker guided new RCTs?

29 FINNAKI long termevaluation Long-termmortality: 1 and 5 years Quality of life after AKI Cost-effectivenessanalysis of AKI

30 Study Group Central Finland Central Hospital: Raili Laru-Sompa, Anni Pulkkinen, Minna Saarelainen, Mikko Reilama, Sinikka Tolmunen, Ulla Rantalainen, Marja Miettinen East Savo Central Hospital: Markku Suvela, Katrine Pesola, Pekka Saastamoinen, Sirpa Kauppinen Helsinki University Central Hospital: Ville Pettilä, Kirsi-Maija Kaukonen, Anna-Maija Korhonen, Sara Nisula, Suvi Vaara, Raili Suojaranta-Ylinen, Leena Mildh, Mikko Haapio, Laura Nurminen, Sari Sutinen, Leena Pettilä, Helinä Laitinen, Heidi Syrjä, Kirsi Henttonen, Elina Lappi, Hillevi Boman Jorvi Central Hospital: Tero Varpula, Päivi Porkka, Mirka Sivula Mira Rahkonen, Anne Tsurkka, Taina Nieminen, Niina Prittinen. Kanta-Häme Central hospital: Ari Alaspää, Hanna Juntunen, Teija Sanisalo Kuopio University Hospital: Ilkka Parviainen, Ari Uusaro, Esko Ruokonen, Stepani Bendel, Niina Rissanen, Maarit Lång, Sari Rahikainen, Saija Rissanen, Merja Ahonen, Elina Halonen, Eija Vaskelainen Lapland Central Hospital: Meri Poukkanen, Esa Lintula, Sirpa Suominen Länsi Pohja Central Hospital: Jorma Heikkinen, Timo Lavander, Kirsi Heinonen, Anne-Mari Juopperi, Middle Ostrobothnia Central Hospital: Tadeusz Kaminski, Fiia Gäddnäs, Tuija Kuusela, Jane Roiko North Karelia Central Hospital: Sari Karlsson, Matti Reinikainen, Tero Surakka, Helena Jyrkönen, Tanja Eiserbeck, Jaana Kallinen Satakunta Hospital district: Vesa Lund, Päivi Tuominen, Pauliina Perkola, Riikka Tuominen, Marika Hietaranta, Satu Johansson South Karelia Central Hospital: Seppo Hovilehto, Anne Kirsi, Pekka Tiainen, Tuija Myllärinen, Pirjo Leino, Anne Toropainen Tampere University Hospital: Jyrki tenhunen, Anne Kuitunen, Ilona Leppänen, Markus Levoranta, Sanna Hoppu, Jukka Sauranen, Atte Kukkurainen, Samuli Kortelainen, Simo Varila Turku University Hospital: Outi Inkinen, Niina Koivuviita, Jutta Kotamäki, Anu Laine Oulu University Hospital: Tero Ala-Kokko, Jouko Laurila, Sinikka Sälkiö Vaasa Central Hospital: Simo-Pekka Koivisto, Raku Hautamäki, Maria Skinnar

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