2.1 - Acute Kidney Injury

Question 1

What is an AKI?

Answer 1

• It is a sudden decline in renal perfusion causing impaired renal function with a decrease in GFR and urine output with an accumulation of nitrogenous waste products in the blood as demonstrated by an elevated in plasma creatinine (Cr) and blood urea nitrogen (BUN) levels.
• An abrupt (within hours) decrease in kidney function, which encompasses both injury (structural damage) and impairment (loss of function).
• May be acute and rapidly progressive and the process may be reversible.
• Commonly results from extracellular volume depletion, decreased renal blood flow, or toxic/inflammatory injury to kidney cells that results in alterations in renal function that may be minimal or severe
• Even small changes in renal function may be associated with significant morbidity and mortality

Question 2

How is AKI defined?

Answer 2

It is defined as any of the following:

• Increase in serum creatinine by 0.3mg/dL or more within 48 hours
• Increase in serum creatinine by 1.5 times or more baseline, within the prior 7 days
• Urine volume less than 0.5mL/kg/hour for at least 6 hours.

Question 3

What are some geriatric considerations for AKI?

Answer 3

Nephrons start to die at age 40 y.o; by the time a person reaches 80 years old 20% of their nephrons are lost.

Question 4

What are the 3 types of AKI?

Answer 4

1. Pre-renal (hypo-perfusion)
2. Intra-renal (disorders involving the renal parenchymal or interstitial tissue)
3. Post-renal ( disorders associated with urinary tract obstruction)

Question 5

What causes pre-renal AKI?

Answer 5

• Hypovolemia
• Hemorrhagic blood loss (trauma, GI bleeding, post-partum hemorrhage)
• Loss of plasma volume (burns, peritonitis)
• Water and electrolyte losses ( severe vomiting/diarrhea, intestinal obstruction, uncontrolled DM, inappropriate use of diuretics)
• Systemic hypotension or hypo-perfusion
• Septic shock
• Cardiac failure or shock
• Massive pulmonary embolism
• Stenosis or clamping of renal artery
• Increased intraabdominal pressure (compartment syndrome)
• Medications: NSAIDs, Aminoglycosides, Radiocontrast dyes, Amphotericin, Norepinephrine

Question 6

What causes intra-renal AKI?

Answer 6

• Acute tubular necrosis (post-ischemic or nephrotoxic medication)
• Glomerulopathies
• Acute interstitial necrosis (tumors or toxins)
• Vascular damage
• Malignant hypertension, vasculitis
• Coagulation defects
• Renal artery/vein occlusion
• Bilateral acute pyelonephritis

Question 7

What causes post-renal AKI?

Answer 7

• Obstructive uropathies (usually bilateral, fibrosis)
• Ureteral destruction (edema, tumors, stones, clots)
• Bladder neck obstruction (enlarged prostate)
• Neurogenic bladder

Question 8

What are the 3 stages of AKI?

Answer 8

Stage 1: Serum Cr. 1.5-1.9 times baseline OR > or equal to 0.3 mg/dL increase

Stage 2: Serum Cr 2.0-2.9 times baseline

Stage 3: Serum Cr 3.0 times baseline OR > or equal to 4.0mg/dL increase OR Initiation of renal replacement therapy

Question 9

Describe the pathophysiology associated with pre-renal AKI

Answer 9

• MOST common cause of AKI
• Results from inadequate kidney perfusion
• During early phases of hypo-perfusion, protective auto regulatory mechanisms maintain GFR at a relatively constant level through afferent arteriolar dilation and efferent arteriolar vasoconstriction (mediated by angiotensin II).
• The GFR ultimately declines due to the decrease in filtration pressure.
• Results in increased tubular sodium and water reabsorption ( in an attempt at re-expansion of circulating blood volume)
• Failure to restore blood volume or blood pressure and oxygen delivery can cause cell injury and acute tubular necrosis and apoptosis or acute interstitial necrosis, a more severe form of AKI

Question 10

Describe the pathophysiology associated with ATN caused by ischemia (a form of intra-renal AKI)

Answer 10

ATN caused by ischemia:

• MOST common cause of intra-renal AKI
• Occurs most often after surgery or severe sepsis.
• Ischemia and reduced levels of ATP generate toxic oxygen free radicals with a loss of antioxidant protection that causes cell swelling, injury and necrosis.
• Activation of inflammatory cells (neutrophils, macrophages and lymphocytes) and complement and release of inflammatory cytokines contribute to tubular injury
• Transport of sodium and other molecules is disrupted with damage primarily to proximal tubular epithelium and shedding of the brush boarder with the appearance of tubular granular casts in the urine.

Question 11

Describe the pathophysiology associated with ATN caused by nephrotoxic substances (a form of intra-renal AKI)

Answer 11

ATN caused by nephrotoxic substances:

• Caused by radiocontrast media and antibiotics (aminoglycosides) as drugs accumulate in renal cortex, such as Cox 1 & 2 inhibitors
• Endogenous substances that are toxic to renal tubules are: myoglobin (oxygen transporting substances in muscles) and hemoglobin
• Necrosis and tubular cell apoptosis caused by nephrotoxins usually limited to the proximal tubules.

Question 12

Describe the pathophysiology associated with post-renal AKI

Answer 12

• Rare & usually occurs in urinary tract obstruction that affects the kidney bilaterally
• Obstruction causes an increase in intraluminal pressure upstream from the site of obstruction with a gradual decrease in GFR.
• Pattern of several hours of anuria with flank pain followed by dysuria is a characteristic finding.

Question 13

What are the 4 phases of AKI?

Answer 13

1. Initiation phase
2. Extension phase
3. Maintenance phase
4. Recovery phase

Question 14

What occurs during the initiation phase of AKI?

Answer 14

• Phase of reduced perfusion or toxicity in which renal injury is evolving
• Usually lasts 24-36 hours
• Prevention of injury is possible in this phase.

Question 15

What occurs during the extension phase of AKI?

Answer 15

In progressive ischemia, there is infiltration of inflammatory cells, mostly neutrophils; release of cytokines; inflammation and cell injury contributing to tubular obstruction and back leak.

Question 16

What occurs during the maintenance phase of AKI?

Answer 16

• Also called oliguric phase
• Period of established renal injury and dysfunction after the initiating event has been resolved
• May last from weeks to months
• Urine output is lowest in this phase
• Serum creatinine, BUN, and potassium levels increase
• Metabolic acidosis develops and there is salt and water overload

Question 17

What occurs during the recovery phase of AKI?

Answer 17

• The interval when renal injury is repaired and normal renal function is re-established
• GFR returns toward normal but the regenerating tubules cannot concentrate the filtrate.
• Diuresis is common (3-4 Liters/day) during this phase with decreased creatinine and urea levels and an increase in creatinine clearance
• Polyuria can result in excessive loss of sodium, potassium and water.
• Fluid and electrolyte balance requires careful maintenance.

Question 18

What are the subjective/physical exam findings associated with AKI?

Answer 18

• The clinical presentation varies with cause and severity of renal injury and the patient’s co-morbidities
• Mild to moderate AKI- patients commonly asymptomatic
• Severe AKI – may be symptomatic and present with:
  
  • Fatigue
  • Anorexia
  • Nausea
  • Vomiting
  • Weight gain
  • Edema
    
    • Proteinuria in renal failure leads to loss of albumin and edema
    • Edema is most common in the legs and ankles especially after standing all day. However in the a.m. periorbital edema is common during the early phase of renal failure.
• In later stages, fluid may collect around the heart and abdomen
• When there is fluid all over the body, it is termed anasarca.
• Oliguria (<400mL urine o/p per day)
• Anuria (< 1oomL urine o/p per day)
• Normal volumes of urine ( as in non-oliguric AKI)
• Uremic encephalopathy (asterixis- flapping hand tremors, declining mental status)
• Anemia
• Bleeding (caused by uremic platelet dysfunction)

Question 19

What is oliguria?

Answer 19

• Defined as less than 400mL of urine output per day
• Can occur in AKI

Question 20

What are the 3 causes of oliguria?

Answer 20

1. Alterations in renal blood flow:

• In response to ischemia, blood flow is directed to renal medulla
• If ischemia continues, tubular sodium reabsorption fails and tubule-glomerular feedback activates RAAS
• Subsequent arteriolar vasoconstriction and decreased GFR occurs.
• Damaged endothelium and leukocyte activation activate coagulation and further impede microcirculatory blood flow, contributing to ischemia, reperfusion injury and decreased GFR.

2. Tubular obstruction:

• Necrosis of tubules causes sloughing of cells, cast formation and ischemic edema that results in tubular obstruction, which in turn….
• Causes a retrograde increase in pressure and reduces the GFR.
• Renal failure can occur within 24 hours

3. Tubular back leak:

• Glomerular filtration remains normal, but tubular reabsorption or ‘leak’ of filtration is accelerated as a result of permeability caused by ischemia and increased tubular pressure from obstruction. Obstruction and back-leak probably occur concurrently.

Question 21

What laboratory tests are done to diagnose AKI?

Answer 21

• Urinalysis: the MOST important non-invasive test in the initial workup of AKI
• Calculate Fractional excretion of sodium (FENa) if oliguria is present.
• Complete blood count (CBC)
• BUN/Serum Creatinine level – compare to previous levels if available; will be elevated
• Hyperkalemia and hyponatremia is associated with AKI
• Metabolic Acidosis: Low Bicarbonate level; results from the inability of the kidneys to excrete hydrogen; renal reabsorption of the filtered bicarbonate is impaired.

Imaging Studies:

• KUB (Kidney, ureter, bladder) x-ray of abdomen- to rule out stones and presence of two (2) kidneys
• Renal ultrasound f- should be performed on most patients with AKI to rule out obstruction and determine post void residual; also helpful in diagnosing extra-renal causes of obstruction (pelvic tumors)
• CT or MRI renal protocol may be required

Renal Biopsy:

• Reserved for patients in whom the diagnosis of pre-renal, or post-renal causes of AKI is unclear

Question 22

How do you calculate Calculate Fractional excretion of sodium (FENa)?

Answer 22

FENA = (100 x (urinary Na x Serum Creatinine)) / (Serum Na x urinary Creatinine)

• FENa < 1% < 1% indicated pre-renal cause
• FENa > 1 % indicates intrinsic cause
• FENa > 2-4% indicates post-renal cause

Question 23

How do you manage a patient with AKI?

Answer 23

• Nephrology consult
• After AKI is diagnosed management is primarily supportive in nature.
• Therapy may include catheter drainage, urethral stents or percutaneous nephrostomy
• Treat underlying cause
• Correct fluid, electrolyte and uremic abnormalities
• Prevent complications
• Adjust intake to output on the basis of fluid status. Take the use of diuretics into consideration since most patients are overloaded.
• The volume depleted patient is usually resuscitated with 0.9NS
• Maximize cardiac function and maintain optimal blood pressure for renal perfusion
• Discontinue offending medications

Question 24

What 3 complications can occur from AKI?

Answer 24

1. Nutritional deficiencies

• AKI patients are in a catabolic state; therefore, they can easily become nutritionally deficient
• Total caloric intake: 30-45 kcal/kg/day – primarily from lipids and carbohydrates
• Non-dialysis patients – protein restriction to < 0.6gms/kg/day
• Dialysis patients – protein intake should be < 1 grams/kg/day
• Low potassium and low sodium diet

2. Hyperkalemia:

• consider kayexalate or IV administration of Calcium (10ml in 10% solution of calcium gluconate) for temporary reversal of neuromuscular effects of hyperkalemia.
• Potassium can be temporarily shifted into the intracellular compartment with the use of IV insulin (10 units) and glucose (25gms), inhaled Beta-agonist or IV sodium bicarbonate (150mEq in 1L D5W)
• Dialysis is the definitive treatment in patients with significantly elevated potassium levels and renal failure.

3. Acidosis:

• treated IV or orally with sodium bicarbonate when serum HCO3 is less than 15mEq/L or pH is lower than 7.2

Question 25

What are the indications for hemodialysis in patients with AKI?

Answer 25

• Between 20-60% of patients with AKI need short term dialysis
• Indications for hemodialysis included: uncontrolled hyperkalemia, severe metabolic acidosis, severe volume overload, encephalopathy and pericarditis
• A pericardial friction rub is a sign of uremic pericarditis; It is an indication for dialysis as it can lead to pericardial tamponade

Question 26

What measures are done to help the patient recover from AKI?

Answer 26

• The kidneys may recover from AKI, but it can take 3-12 months
• There are many factors that play a role in recovery. The patient must be off all nephrotoxic medications, control co-morbidities, such as hypertension and diabetes
• Follow-up with a nephrologist always to monitor BUN and Cr closely.
• Avoid all radiologic studies involving the use of IV contrast until full recovery has occurred.