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OMG: Not Another Biomarker Talk - Forni
1. Lui G Forni : Consultant Intensivist & Nephrologist
Faculty of Health Sciences : University of Surrey
The Injured Kidney:
AKI: Who Will Get It ??
OMG : Not Another
Biomarker Talk…
15. Incidence and outcomes of acute kidney injury in intensive care units:
AVeterans Administration study
CV Thakar et al,
Crit Care Med 2009
Risk
Dependent on
Cause
AcuteKidneyInjury:WhoWillGetIt?
22. AcuteKidneyInjury:WhoWillGetIt?
“a characteristic that is objectively
measured and evaluated as an
indicator of normal biological
processes, pathogenic processes,
or pharmacologic responses to a
therapeutic intervention”
Biomarkers…..
33. AcuteKidneyInjury:WhoWillGetIt?
Total 260 740 1000
AKI (PT+ve) 180 20 260
No AKI (PT-ve) 80 720 720
69%
Sensitivity
97%
Specificity
“AKI” As Determined by PT
Even the perfect test
would give imperfect
results…...
36. Initial Cellular Insults
Oxidative/Inflammatory Stress
DNA damage
G1 Cell-Cycle arrest
G1
G2
S
(DNA
synthesis)
InterphaseCytokinesis
Mitosis
Mitotic phase (M)
[TIMP-2] [IGFBP7]
Peroxidized lipids
Chemical exposure
PAMPSDAMPS
Reactive oxygen
species
Oxidized proteins
[IGFBP7]
[TIMP-2]
P53
P21
P27
CyclE
CDK2
CyclD
CDK4
Markers of Cell-Cycle Arrest
p53/p21
signaling
involved
in CCA
G1 = Gap 1
(Cell Growth/Preparation
for DNA Synthesis)
37. Conclusions
• Over 50% of our Patients Currently Get AKI
• Overall Poor Outlook Probably Reflects
– Multisystem effects of renal injury
– Underlying cause of the AKI
• We Should Probably Abandon the Slavish
Chase for a RenalTroponin….
AcuteKidneyInjury:WhoWillGetIt?
38. Conclusions
• We need to
start listening
to what the
new molecules
are telling us..
AcuteKidneyInjury:WhoWillGetIt?
Editor's Notes
Major routes of Cr metabolism in the mammalian body. The most part (up to 94%) of Cr is found in muscular tissues. Because muscle has virtually no Cr-synthesizing capacity, Cr has to be taken up from the blood against a large concentration gradient by a saturable, Na+- and Cl−-dependent Cr transporter that spans the plasma membrane (□). The daily demand for Cr is met either by intestinal absorption of dietary Cr or by de novo Cr biosynthesis. The first step of Cr biosynthesis probably occurs mainly in the kidney, whereas the liver is likely to be the principal organ accomplishing the subsequent methylation of guanidinoacetic acid (GAA) to Cr. It must be stressed that the detailed contribution of different bodily tissues (pancreas, kidney, liver, testis) to total Cr synthesis is still rather unclear and may vary between species (see text). The muscular Cr and PCr are nonenzymatically converted at an almost steady rate (∼2% of total Cr per day) to creatinine (Crn), which diffuses out of the cells and is excreted by the kidneys into the urine.