AKI (Part I) Flashcards
1
Q
What is the risk factor for CKD & ESRF?
A
AKI
2
Q
What is the definition of AKi?
A
- Reduced UO < 0.5ml/kg/hr for 6hrs
- Increased creatinine > 1.5 of baseline in 7 days
- Increased creatinine > 0.3mg/dL or 26.5 micromol/L in 48hrs
3
Q
Stimulants from the production of ADH?
A
- Stress
- Pain
- Hypovolaemia
4
Q
What is KDIGO?
A
Kidney Disease Improving Global Outcomes - Established in 2012
5
Q
What is AKD ?
A
AkI persisting for > 7 days
6
Q
What is CKD?
A
AKD persistent until day 90
7
Q
What is creatinine?
A
- Metabolite of creatine phosphate
- Falls in critical illness
8
Q
What is creatine phosphate?
A
Synthesized from the below in the liver & kidney;
- Amino acids
- Glycine
- Arginine
9
Q
Creatine phosphate energy potential?
A
Mobilizable reserve of high energy phosphate in skeletal muscles
10
Q
Determinants of creatinine production?
A
- Determined by muscle mass
- Meat intake
- Amount of creatine generated in the liver & kidney
11
Q
Limitations of creatinine as a marker for renal function?
A
- Takes 24-36hrs to rise after renal insult
- Drug induced change in conc. w/o change in renal function
- Unreliable in sepsis, liver disease or muscle wasting
- Affected by volume status - Undiagnosed in hypervolaemia
- Baseline required
12
Q
Analytic assessment of creatinine?
A
Jaffe-based assay
13
Q
Drugs interfering with creatinine?
A
- Cimetidine - Rise of creatinine
- Trimethoprim - Rise of creatinine
14
Q
Conditions causing oliguria?
A
- Fasting
- Surgery
- Stress
- Hypovolaemia
- Pain
- Trauma
15
Q
Physiologic & pathologic oliguria?
A
See image attached
16
Q
What is cystatin C?
A
- Produced by all nucleated cells
- Low MW facilitating glomerular filtration
- Reabsorbed in the renal tubules
- Catabolized in the proximal tubular cells
- Conc influenced by steroids & thyroid Fx
- More accurate in critically ill than creatinin
- Shorter half-life than creatinine
- Presence in urine is a marker of kidney injury
17
Q
Furosemide stress test?
A
- 1mg/kg or 1.5mg/kg if furosemide in last 7 days
- If UO is < 200ml in 2 hrs - Risk of progression of AKI and RRT
18
Q
Furosemide action?
A
- Binds to albumin
- Actively secreted into the tubular lumen in PCT
- Delivered to the thick ascending limb of LoH
- High sensitivity & specificity for RRT
19
Q
Usefulness of creatinine?
A
It reflects glomerular filtration
20
Q
New biomarkers reflecting tubular stress?
A
TIMP-2 x IGFBP-7
21
Q
New biomarkers reflecting tubular damage?
A
- NGAL
- KIM-1
- L-FABP
22
Q
New biomarkers reflecting tubular inflammation?
A
- IL-18
- CCL14
23
Q
What is subclinical AKI?
A
Increase in biomarker levels without increase in creatinine
24
Q
What is functional AKI?
A
Increase in creatinine levels without increase in biomarkers
25
What is subclinical injury?
Rise is biomarker levels without increase in creatinine
26
Creatinine - Is it an early or late marker of AKI?
This is a late maker of AKI
27
What is the enzyme released from tubular cells after injury in the - Proximal Renal Tubule?
- HRTE-1 (Proximal renal tubular epithelial antigen)
- Alpha-glutathione S-transferase (Alpha-GST)
- Pi-glutathione S-transferase (pi-GST)
- GGT - Gamma-glutamyltranspeptidase
- AAP - Alanine Aminopeptidase
- LDH
- NAG - N-acetyl-beta-glucosaminidase
- ALP
28
What is KIM-1 (Kidney Injury Molecule) ?
- MW =38.7kDa
- Type-1-Transmembrane Glycoprotein
- Undetectable in normal kidney tissue and urine
- Present after kidney injury
- Plays a role in renal injury & repair
29
What is interleukin-18?
- It is a 22kDa molecule
- Pro-inflammatory cytokine
- Recruits neutrophils during ischaemic injury
30
When is interleukin-18 present in the kidney?
Present in the kidney after ischaemic-reperfusion injury
31
Time from injury to detection of interleukin-18 in urine ?
- In the first 6 hours
- Peaks at 12 - 18 hours
32
What is Neutrophil Gelatinase-associated lipocalin (NGAL)?
- Its is a 25kDa molecule
- Linked to inflammation & infection
- Results from tubular production & secretion
- Freely filtered by glomerulus
33
Time of kidney injury to detection of Neutrophil Gelatinase-associated lipocalin (NGAL) in urine?
- 2 hours after ischaemic or nephrotoxic injury
34
What is the mechanism of action of Neutrophil Gelatinase-associated lipocalin (NGAL) ?
- Binding to iron-siderophore complexes
- Bacteriostasis by inhibiting iron uptake by bacteria
- Upregulation of heme oxygenase-1
- Overall protective action on tubular cells
35
What is the main sites of production of Neutrophil Gelatinase-associated lipocalin (NGAL) ?
- Thick ascending limb of LoH
- Collecting duct
36
What is the usefulness of Neutrophil Gelatinase-associated lipocalin (NGAL) ?
- Predict the onset of AKI
- Predict the course of AKI
37
How is Neutrophil Gelatinase-associated lipocalin (NGAL) tested?
- Available as a bedside test
38
What is L-FABP (Urinary Liver-type fatty acid-binding protein) ?
- Gene expressed in the renal cortex
- It is 14kDa in weight
- Localized in the PCT
39
What does L-FABP (Urinary Liver-type fatty acid-binding protein) signify?
- Proximal tubular epithelial cell stress
- Severity of ischaemic tubular injury
- Elevated after cardiac surgery
40
What is the peak time to identifying L-FABP (Urinary Liver-type fatty acid-binding protein) ?
- This is 6 hours
41
What is urinary Tissue Inhibitor of Metalloproteinases - TIMP & Insulin-like growth factor binding protein (7) - IGFBP7 ?
- Involved in G1 cell cycle arrest
- Marker of tubular stress
42
Urinary Tissue Inhibitor of Metalloproteinases - TIMP & Insulin-like growth factor binding protein (7) - IGFBP7 are a strong predictor for?
Development of KDIGO 2/3 within 12 hours.
43
What are CCL14?
- Member of the chemokine family
- Role is leukocyte chemotaxis
- Tissue injury and repair process
44
Properties of CCL14?
- Binds avidly to chemokine receptors
- Important for monocyte/macrophage recruitment
- Increased urinary secretion predicts persistent AKI
45
What diseases is CCL14 implicated for proinflammatory chemotaxis ?
- RA
- Sclerosis
- Lupus
