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,
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
RIFLE & AKIN & KDIGO
KDIGO 2012 2007 2004 0.3 mg/dl = 26 umol/L 0.5 mg/dl = 44 umol/L 4 mg/dl = 354 umol/LAKIN vs. RIFLE
AKIN vs. RIFLE
Joannidis et al. ICM 2009
• 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
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; 2
AKI biomarkers
Devarajan, P. Nephrology 2010
Subclinical AKI
Haase, Devarajan et al.
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)
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) 67.2AKI long-term prognosis
Wald, R., R. R. Quinn, et al. JAMA 2009
AKI mortality
AKI mortality
AKI Hospital Mortality % Stage 3 / RIFLE F Hospital Mortality % AKI Long-term mortality 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. CritCareMed 2008;36:3178-83
Kolyada AY, Tighiouart H et al. A geneticvariant of hypoxia-induced factor-1a is associatedwithadverseoutcomes in acutekidneyinjury. KidneyInt 2009; 75:1322-1329.
FINNAKI
• AKI study
• RRT –substudy
• Finnsepsis II
• Genetic substudy
FINNAKI RRT – substudy FINNSEPSIS II Genetic study Cardiac surgery substudy RRT outside ICU
Study population
ICU admission AKI study Excluded patients Cardiac surgery substudy Genetic substudy RRT -substudy RRT – treated AKI patients outside 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 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)
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 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
• 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
FINNAKI
FINNAKI
Under 18 years Elective admission < 24h On chronic RRT Organ donor Initiation of chronic RRT Declined / No consent NonresidentPreviously in study with RRT
Over 5 days in study in another ICU Intermediate care
Emergency admission Elective admission >24 h
Inclusion
• 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
• 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 to
21.06.2012
• 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.)
FINNAKI
FINNAKI –near future
• Population –basedincidence of AKI
• RRT -substudy
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?
FINNAKI –long termevaluation
• Long-termmortality: 1 and 5 years
• Quality of life after AKI
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