What did we aim to learn fromthe FINNAKI -study
Maija Kaukonen, MD, PhD, EDICSpecialist in anesthesiology and intensive care
Specialist in clinical phramacologyIntensive Care Units, Division of Anaesthesia
and Intensive Care Medicine,Helsinki University Central Hospital, Helsinki, Finland
Acute Kidney Injury -AKI
• Definition and classification of AKI:RIFLE 2004, AKIN 2007, KDIGO2012
• These criteria are based inmeasurements of serum creatinine orurine output
RIFLE & AKIN & KDIGO
KDIGO 2012
20072004
0.3 mg/dl =26 umol/L
0.5 mg/dl =44 umol/L
4 mg/dl =354 umol/L
AKIN vs. RIFLE
Joannidis et al. ICM 2009
AKIN vs. RIFLE
Joannidis et al. ICM 2009
• RIFLE: 9% of patients unrecognised thatwere recognised by AKIN– 90% of thse were AKIN Stage 1 patients
• AKIN: 26.9% of patients unrecognised thatwere recognised by RIFLE– 30% of these were RIFLE I– 18% of these were RIFLE F
AKI progression
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
AKI biomarkers
Bagshaw SM. Bellomo R. Et al. Canadian Journal of Anaesthesia; 2Bagshaw SM. Bellomo R. Et al. Canadian Journal of Anaesthesia; 2010010..
AKI biomarkers
Devarajan, P. Nephrology 2010Devarajan, P. Nephrology 2010
Subclinical AKI
Haase, Devarajan et al.Haase, Devarajan et al. J Am Coll Cardiol. 2011 Apr 26;57(17):1752J Am Coll Cardiol. 2011 Apr 26;57(17):1752--61.61.
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)
Population-basedincidence of AKI
AKI incidence –ICU patients
AKI %
Cruz 2007 (2164) 10.8
Thakar 2009 (323 359) 22.0
Joannidis 2009 (16 784) 28.5
Ostermann 2007 (41 972) 35.8
Bagshaw 2008 (120 123) 37.1
Hoste 2006 (5383) 67.2
AKI long-term prognosis
Wald, R., R. R. Quinn, et al. JAMA 2009Wald, R., R. R. Quinn, et al. JAMA 2009..
AKI mortalityAKI mortality
AKIHospital
Mortality%
Stage 3 /RIFLE FHospitalMortality
%
AKILong-termmortality
Hoste 2006 (5383) 13.3 26.3 -
Ostermann 2007 (41 972) 56.8 -
Bagshaw 2008 (120 123) 24.5 32.6 -
Joannidis 2009 (16 784) 36.4 41.2 -
AKI –genetics
• AngiotensinConvertingenzyme I/D geneticpolymorphism– 180 ICU patients, association with AKI (RIFLE –criteria)
• Hypoxia-inducedfactor 1– 241 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. CritCareMed2008;36:3178-83Kolyada AY, Tighiouart H et al. A geneticvariant of hypoxia-induced factor-1a is associatedwithadverseoutcomes in acutekidneyinjury. KidneyInt 2009; 75:1322-1329.Jaber BL, RaoMadhumathi, Guo D et al. Cytokinegenepromoterpolymorphisms and mortality in acuterenalfailure. Cytokine 2004; 25:212-219
FINNAKI
• AKI study• RRT –substudy• Finnsepsis II• Genetic substudy• Cardiac surgery substudy
FINNAKI
RRT –substudy
FINNSEPSIS II
Genetic study
Cardiac surgerysubstudy
RRT outsideICU
Study population
ICU admission
AKI study
Excludedpatients
Cardiac surgerysubstudy
Geneticsubstudy RRT -substudy
RRT –treated AKIpatientsoutside ICU
FINNSEPSIS II
Patientflow
• The aims of the study– Incidence of AKI in ICU and in Finnish population– Risk factors for AKI– Outcome of AKI
Renal recoveryMortality (90 –day, 6 month, 12 month, 5 –year)Quality of life after AKICost-utility of the treatment of AKI
– The mechanism of AKI; apoptosis/endothelial damage andinflammatory markers (eg. P-DNA, MMP-2, MMP-8, MMP-9,IL-6, TIMP-1, TIMP-2, PINP, PIIINP ja ICTP, caspases)
– New biomarkers of AKIPredictive value for AKI, RRT –treatment and mortality(e.g. P-/U-NGAL, U-NAG, U-KIM-1, U-IL-18)
FINNAKI
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
• Incidence of septic AKI in ICU and inFinnishpopulation
• Riskfactors for septic AKI• Outcomeof septic AKI
RenalrecoveryMortality (90 –day, 6 month, 12 month, 5 –year)Quality of life afterseptic AKICost-utility of the treatment of septic AKI
• Biomarkers of septic AKI
FINNSEPSIS II -substudy
• Incidence and interrelation of cardiac injuryand AKI measured with new cardiac biomarkers
• Correlation of acute kidney injury biomarkersand cardiac injury biomarkers with risk scoring(Euroscore, Syntax), morbidity and mortality
Cardiac surgery substudy
FINNAKIFINNAKI
Under 18 yearsElective admission < 24hOn chronic RRTOrgan donorInitiation of chronic RRTDeclined / No consentNonresidentPreviously in study with RRTOver 5 days in study in another ICUIntermediate care
Emergency admissionElective admission >24 h
InclusionInclusion ExclusionExclusion
• 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
Collection of data
• Studyprotocolpreparation in 2010• Pilotstudy 3.-4.5.2011• Patientrecruitment 1.9.2011-1.2.2012
– Extension for severesepsispatients and RRT –patients to 30.04.2012
• Cardiacsurgerysubstudyrecuritmentup to21.06.2012
FINNAKI –execution
• 5853 ICUadmissionsduringpatientrecruitmentperiod• 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 isongoing (400 patientsrecruited28.05.)
FINNAKI
FINNAKI –near future
• Population –basedincidence of AKI• RRT -substudy• FINNSEPSIS II
FINNAKI - biomarkers
• Earlierdiagnosis of AKI in future– Validationof new biomarkers in unselected ICU
patientcohort– NGAL, IL-18, KIM1
• Biomarkerpanelfor diagnosing AKI inunselected ICU patients?
• Progress and resolutionof AKI in light ofnew biomarkers?
• Biomarker –guided new RCTs?
FINNAKI –long termevaluation
• Long-termmortality: 1 and 5 years• Quality of life after AKI• Cost-effectivenessanalysis of AKI
Central Finland Central Hospital: Raili Laru-Sompa, Anni Pulkkinen, Minna Saarelainen, Mikko Reilama, SinikkaTolmunen, Ulla Rantalainen, Marja Miettinen
East Savo Central Hospital: Markku Suvela, Katrine Pesola, Pekka Saastamoinen, Sirpa KauppinenHelsinki 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, NiinaPrittinen.
Kanta-Häme Central hospital: Ari Alaspää, Hanna Juntunen, Teija SanisaloKuopio University Hospital: Ilkka Parviainen, Ari Uusaro, Esko Ruokonen, Stepani Bendel, Niina Rissanen, Maarit Lång,
Sari Rahikainen, Saija Rissanen, Merja Ahonen, Elina Halonen, Eija VaskelainenLapland Central Hospital: Meri Poukkanen, Esa Lintula, Sirpa SuominenLänsi Pohja Central Hospital: Jorma Heikkinen, Timo Lavander, Kirsi Heinonen, Anne-Mari Juopperi,Middle Ostrobothnia Central Hospital: Tadeusz Kaminski, Fiia Gäddnäs, Tuija Kuusela, Jane RoikoNorth Karelia Central Hospital: Sari Karlsson, Matti Reinikainen, Tero Surakka, Helena Jyrkönen, Tanja Eiserbeck,
Jaana KallinenSatakunta Hospital district: Vesa Lund, Päivi Tuominen, Pauliina Perkola, Riikka Tuominen, Marika Hietaranta, Satu
JohanssonSouth Karelia Central Hospital: Seppo Hovilehto, Anne Kirsi, Pekka Tiainen, Tuija Myllärinen, Pirjo Leino, Anne
ToropainenTampere University Hospital: Jyrki tenhunen, Anne Kuitunen, Ilona Leppänen, Markus Levoranta, Sanna Hoppu, Jukka
Sauranen, Atte Kukkurainen, Samuli Kortelainen, Simo VarilaTurku University Hospital: Outi Inkinen, Niina Koivuviita, Jutta Kotamäki, Anu LaineOulu University Hospital: Tero Ala-Kokko, Jouko Laurila, Sinikka SälkiöVaasa Central Hospital: Simo-Pekka Koivisto, Raku Hautamäki, Maria Skinnar
Study GroupStudy Group
Top Related