AKI

Question 1

Define Acute Kindey Injury (AKI)

Answer 1

• Clinical syndrome that results in abrupt decline in GFR that decreases elimination of nitrogen waste products and causes dysregulation of volume and electrolytes
  
  • Creatinine is rising and urine output in decreasing

Question 2

AKIN criteria for AKI

Answer 2

Cr Criteria Urine Output (UO) Criteria

Stage 1 Increased CrX1.5 or ≥.3mg/dL UO <.5mg/kg/hr X6hr

Stage 2 Increased CrX2 UO <.5mg/kg/hr X12hr

Stage 3 Increased CrX3 or ≥4mg/dLX UO <.5mg/kg/hr X24hr or anuria

acute rise of ≥ .5mg/dl X12hr

Question 3

Main types of AKI

Answer 3

• AKI is grouped anatomically into 3 categories

1. Pre-renal: Not enough circulation reaching the kidneys (i.e., hypovolemia)
2. Renal: Something wrong inside of the kidneys
3. Post-renal: Something wrong after the urine in made (i.e., obstruction)

Question 4

Explain Pre-renal AKI

Answer 4

• Imparied renal perfusion resulting in a fall in glomerular capillary filtration pressure. In these cases the tubular function is normal, renal reabsorption of Na⁺ and water is increased, and urine chemistries reveal low urine sodium and concentrated urine.
• Reduction in renal perfusion overwhelms autoregulation and precipates an acute fall in GFR (with less renal hypoperfusion autoregulation would result in arteriolar vasodilation and efferent arteriolar vasoconstriction).

Question 5

Causes of Pre-Renal AKI

Answer 5

• Pre-renal AKI is generally secondary to extracellular fluid depletion
  
  • GI losses - diarrhea, vomiting, prolonged nasogastric drainage
  • Renal losses - diuretics, osmotic diuresis in hyperglycemia
  • Dermal losses -burns, excessive sweating
  • Sequestration of fluid - acute pancreatitis, muscle trauma
  • Distributive - have lots of fluid in the body, but intravascular volume is low so not enough fluid is reaching the kidney - ileus, nephrotic syndrome, cirrhosis, vasodilation (sepsis, anaphylaxis, etc.).
  • Decreased CO
  • Constriction of renal arteries - vasoconstrictive drugs (pressors), cocaine, etc.

Question 6

Causes of Post-renal AKI

Answer 6

• Obstruction - blockage of urine flow somewhere in the system
  
  • Renal pelvis - stone, papillary necrosis
  • Ureters - stones, blood clots, retroperitoneal fibrosis
  • Bladder - Prostate, stones, spasm
• Must obstruct all functioning kidney(s) for AKI to occur

Question 7

Explain post-renal AKI

Answer 7

• Blockage creates buildup of urine and pressure all the way back to the kidney. Increased pressure prevents normal fluid flow from high pressure glomerulus to low pressure tubules lowering the GFR.

Question 8

Explain Renal AKI

Answer 8

• There are 4 structures that can be effected in renal AKI
  
  • Tubular
  • Glomerular
  • Interstital
  • Vascular

Question 9

Acute Tubular Necrosis (ATN) Causes

Answer 9

• A type of tubular AKI where the endothelial cells lining the tubules die
• There are 2 main causes of ATN
  
  • Ischemic - from severe/prolonged hypoperfusion of the kidneys
  • Nephrotoxic - from compounds that are toxic to the kidneys
    
    • Endogenous compounds - hemoglobin (hemolysis), myoglobin (rhabdomyolysis)
    • Exogenous - antibiotics, constrast, heavy metals.

Question 10

Explain ATN

Answer 10

• Injury of tubular cells is seen mostly at the straight proximal tubules and the thick ascending limb of the loop of Henle.
• Decrease in GFR is due to reduced filtration from hypoperfusion and from casts and debris obstructing the tubule lumen causing back-leak of filtrate through damaged epithelium (ineffective filtration). (Essentially plugs the renal tubules resulting in increased pressure, making it harder for hydrostatic glomerular pressure to push fluid in Bowmans capsule)
• A common cause is concurrent ACEi/ARB medicaitions with NSAIDs, or continued use of ACEi/ARB with volume depletion (affterent constriction + hypovolemia).

Question 11

Acute glomerulo-nephritis (GN)

Answer 11

• A type pf glomerular AKI
• Inflammation and subsequent damage of the glomeruli leading to hematuria, proteinuria, and abnormally high waste products in the blood.
• Due to antigen-antibody complexes that recruit other immune cells resulting in the release of lysosmal enzymes that damage the podoctyes
• Causes: lupus nephritis, post-strep GN, bacterial endocarditis

Question 12

Acute Interstitial nephritis (AIN)

Answer 12

• A type of interstitial AKI
• Due to allergic reactions to a variety of medications (antibiotics, NSAIDs) or infection/diseases (sacroidosis, legionella, bacterial illness)
• AIN is thought to be immune mediated - immune-mediated infiltration of kidney interstitum by inflammatory cells. Injury to renal cells leads to antigen expression, inflammatory cells infiltration and activation of proinflammatory and chemoattrant cytokines. In AIN, tubular damage leads to renal tubular dysfunction with or without renal failure.
• Drug-induced AIN is a drug hypersenstivity reaction that manifests 7-10days after exposure to culprit drug. Kidney are suspectible to drug-hypersensitivity reactions because of the high renal blood flow, whereby antigens are filtered and it is the major site of excretion of drugs and drug metabolites.

Question 13

Vascular AKI

Answer 13

• Injury to intrarenal vessels decreases renal perfusion reducing GFR.
  
  • Thromobemboli sm
  • Atheroembolism (cholesterol)
  • Microangiopathathies - diseases of small blood vessels - malignant hypertension, pre-eclampsia, HUS/TTP

Question 14

How to differentiate between the different types of AKI

(urine studies)

Answer 14

• Pre-renal - Increases RAAS, FeNa < 1%
• Renal (in all cases you will have proteinuria but in GN it will be very elevated)
  
  • Vascular - urine studies are normal because damage is before glomerulus
  • Glomerular - proteinuria (+3), hematuria (RBCs are dysmorphoric because they had to squeeze through basement membrane), RBC casts
  • ATN - Hemgranular casts, FeNa >10%
  • Interstitial - WBCs, eosinophiluria, white cell casts
• Post-renal - Ultrasound

Question 15

Treatment for AKI

Answer 15

• Important the manage the life-threatening fluid and electrolyte abnormalities. Overall , the main treatment of AKI is to treat the underlying causes (relieve obstruction, relieve hypovolemia, stop culprit medications, etc) and the complications
• Volume
  
  • Volume depletion - administer IV fluid
• Hyperkalemia - calcium, insulin with glucose (drive K into cells)
• Metabolic acidosis - treat with bicarb or dialysis
• Hypocalcemia - administer oral phosphate binders

Question 16

Indications for dialysis in AKI

Answer 16

• Fluid overload that is refractory to diuretics
• Hyperkalemia >6.5mEq/L or rapidly raising K levels that are refractory to meds
• Metabolic acidosis when bicarb administration is contraindicated (ex. volume overloaded, lactic acidosis, ketoacidosis)
• Signs of uremia - pericarditis, neuropathy, unexplained decline in mental status, fatigue, itchy, nausea, vomiting