AKI in severe sepsis. Keir and Kellum. 2015. JVECC

Question 1

What does RIFLE stand for?

Answer 1

Risk
Injury
Failure
Loss of kidney function
End-stage kidney disease

Question 2

How are the RIFLE stages defined?

Answer 2

Question 3

What are the stages of KDIGO and how are they defined?

Answer 3

Question 4

On histopathology how does sepsis from AKI differ from AKI from nephrotoxins or ischemia>

Answer 4

• Sepsis-induced AKI typically has only mild histological changes, some patchy tubular changes with little necrosis
• Ischema/Nephrotoxin-induced AKI: diffuse glomerular and tubular damage with extensive necrosis

Question 5

What pro-inflammatory cytokine concentration has been correlated with the risk of AKI in people with CAP?

Answer 5

Interleukin-6

Question 6

Explain how tubular epithelial dysfunction leads to a decreased UOP and increased serum creatinine

Answer 6

• tubular dysfunction results in decreased NaCl absorption –> increased NaCl delivered to macula densa cells –> tubuloglomerular feedback mechanism –> vasoconstriction of afferent arteriole –> decreased GFR
• disruption of tight junctions between renal tubular epithelian cells –> back leakage of tubular fluid across the epithelium
• loss of cellular adhesion to the basement membrane –> shedding of epithelial cells –> casts in urine and blockage of tubules

Question 7

What are the steps following sublethal cellular injury to the kidneys?

Answer 7

repair
* death if damaged beyond recovery
* infiltration of mononuclear cells
* repair or death choice mediated by cyclindependent kinase inhibitors
regeneration
* stem cells appear
proliferation
* marked proliferation of surviving tubular cells
* influenced by growth factor

Question 8

List early markers of AKI

Answer 8

• NGAL
• Kidney injury molecule-1
• cystatin C
• liver fatty acid binding protein
• G1-G0 cell cycle arrest biomarkes (metalloproteinases-2 and inuslin-like growth factor binding protein-7

Question 9

What are the IRIS AKI grades and how are they defined?

Answer 9

Grade I
* non-azotemic, i.e., creatinine < 1.6 mg/dL with 0.3 mg/dL rise

Grade II
* creatinine 1.7-2.5 mg/dL

Grade II
* creatinine 2.6-5.0 mg/dL

Grade III
* creatinine 5.1-10 mg/dL

Grade VI
* creatinine >10.0 mg/dL

Question 10

List biomarkers of early AKI evaluated in dogs

Answer 10

• urinary neutrophil gelatinase-associated lipocalin (NGAL)
• urinary cystatin-C
• urinary NAG (n-acetyl-beta-D-glucosaminidse)
• urinary retinol binding protein

Question 11

How does dopamine improve renal blood flow?

Answer 11

• improves cardiac output through systemic cardiovascular effects
• dilates renal afferent and efferent arterioles via local dopaminergic receptors

Question 12

What are the renal dopamine receptors?

Answer 12

mainly D1 and D5

Question 13

What is the only indication of Furosemide in AKI?

Answer 13

• regulating fluid balance if fluid overloaded

Question 14

What are the current arguments against Dopamine use in AKI?

Answer 14

• negative studies on renal vasodilatory effects
• renal effects seen in healthy patients not preserved in face of AKI
• can cause increased vascular resistance and reduced RBF
• side effects: tachyarrhythmias, myocardial hypoxia, reduced splanchnic blood flow, suppressed T cell function

Question 15

What is the mechanism of action of Fenoldopam?

Answer 15

pure dopamine type-1 receptor agonist
no alpha and beta adrenergic effects

Question 16

What is the theory behind NAC use in AKI?

Answer 16

• restores glutathiones stores
• enhances NO availability