AKI (Part I) Flashcards
What is the risk factor for CKD & ESRF?
AKI
What is the definition of AKi?
- 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
Stimulants from the production of ADH?
- Stress
- Pain
- Hypovolaemia
What is KDIGO?
Kidney Disease Improving Global Outcomes - Established in 2012
What is AKD ?
AkI persisting for > 7 days
What is CKD?
AKD persistent until day 90
What is creatinine?
- Metabolite of creatine phosphate
- Falls in critical illness
What is creatine phosphate?
Synthesized from the below in the liver & kidney;
- Amino acids
- Glycine
- Arginine
Creatine phosphate energy potential?
Mobilizable reserve of high energy phosphate in skeletal muscles
Determinants of creatinine production?
- Determined by muscle mass
- Meat intake
- Amount of creatine generated in the liver & kidney
Limitations of creatinine as a marker for renal function?
- 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
Analytic assessment of creatinine?
Jaffe-based assay
Drugs interfering with creatinine?
- Cimetidine - Rise of creatinine
- Trimethoprim - Rise of creatinine
Conditions causing oliguria?
- Fasting
- Surgery
- Stress
- Hypovolaemia
- Pain
- Trauma
Physiologic & pathologic oliguria?
See image attached
What is cystatin C?
- 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
Furosemide stress test?
- 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
Furosemide action?
- Binds to albumin
- Actively secreted into the tubular lumen in PCT
- Delivered to the thick ascending limb of LoH
- High sensitivity & specificity for RRT
Usefulness of creatinine?
It reflects glomerular filtration
New biomarkers reflecting tubular stress?
TIMP-2 x IGFBP-7
New biomarkers reflecting tubular damage?
- NGAL
- KIM-1
- L-FABP
New biomarkers reflecting tubular inflammation?
- IL-18
- CCL14
What is subclinical AKI?
Increase in biomarker levels without increase in creatinine
What is functional AKI?
Increase in creatinine levels without increase in biomarkers
What is subclinical injury?
Rise is biomarker levels without increase in creatinine
Creatinine - Is it an early or late marker of AKI?
This is a late maker of AKI
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
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
What is interleukin-18?
- It is a 22kDa molecule
- Pro-inflammatory cytokine
- Recruits neutrophils during ischaemic injury
When is interleukin-18 present in the kidney?
Present in the kidney after ischaemic-reperfusion injury
Time from injury to detection of interleukin-18 in urine ?
- In the first 6 hours
- Peaks at 12 - 18 hours
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
Time of kidney injury to detection of Neutrophil Gelatinase-associated lipocalin (NGAL) in urine?
- 2 hours after ischaemic or nephrotoxic injury
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
What is the main sites of production of Neutrophil Gelatinase-associated lipocalin (NGAL) ?
- Thick ascending limb of LoH
- Collecting duct
What is the usefulness of Neutrophil Gelatinase-associated lipocalin (NGAL) ?
- Predict the onset of AKI
- Predict the course of AKI
How is Neutrophil Gelatinase-associated lipocalin (NGAL) tested?
- Available as a bedside test
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
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
What is the peak time to identifying L-FABP (Urinary Liver-type fatty acid-binding protein) ?
- This is 6 hours
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
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.
What are CCL14?
- Member of the chemokine family
- Role is leukocyte chemotaxis
- Tissue injury and repair process
Properties of CCL14?
- Binds avidly to chemokine receptors
- Important for monocyte/macrophage recruitment
- Increased urinary secretion predicts persistent AKI
What diseases is CCL14 implicated for proinflammatory chemotaxis ?
- RA
- Sclerosis
- Lupus
