Acute Kidney Injury

Lecture given:

Summary chart



List the tests required to distinguish acute from chronic renal failure and explain the rationale

Acute Kidney Injury:

  • Increase in serum creatinine by 44mEq/L (0.5 mg/dL) OR
  • An increase in serum creatinine of more than 50% from baseline OR
  • A reduction in the calculated creatinine clearance of 50%
    • Formulae to estimate GFR assume patient is in steady state, which doesn't apply to patients in acute change (works better in CKD). Therefore, if patient's GFR is rising over days/weeks, can assume in AKI

NB: serum creatinine can be confounded by muscle mass, it is secreted as well as filtered, and certain diseases and medications interfere with correlation between serum creatinine and GFR

More accurate techniques of determining GFR in AKI involves nuclear medicine studies and GFR scans. New biochemical markers are being investigated (e.g. Cystatin C)

Etiology of AKI in hospital settings

  • 21% pre-renal causes: decrease in effective circulating volume. volume depletion is most common
    • Adaptive response to severe volume depletion and hypotension with structurally and functionally intact nephrons
  • 45% renal (intrinsic) causes: tubules, interstitium, glomeruli, blood vessel
    • In response to cytotoxic or ischemic insults to the kidney with structural and functional damage
  • 10% post-renal causes
    • Obstruction distal to kidney

Important to rule out pre- and post- renal causes in the beginning because they can be easily and quickly fixed!

Important history questions

  • N/V/D? (volume contraction)
  • Hx of heart disease, liver disease, previous renal disease?
  • Kidney stones, benign prostate hyperplasia? (post renal causes, pelvic malignancy)
  • Any recent illness?
  • Edema, change in urination?
  • New medications? Recent radiology studies? (intrinsic causes)
  • Rashes? (autoimmune)

On physical exam

  • Volume status: vitals
  • Cardiovascular: JVP, rubs (uremeic pericarditis is an emergency because patient is bleeding into the pericardium, causing tamponade)
  • Pulmonary: decrease breath sounds, rales
  • Rash, synovitis (autoimmune: may be allergic interstitial nephritis, vasculitis, livedo reticularis)
  • Large prostate (BPH)
  • Extremities: skin turgor, edema (fluid status - overload or contraction)
  • MMSE (encephalopathic, asterixis)
  • You are trying to look for dangerous signs of kidney failure


  • Urine sediment (U/A): look for casts, cells, protein
  • Urine electrolytes (UNa) and Cr to calculate FeNa (fractional excretion of sodium)
  • Urine osmolarity
  • Urine protein/eosinophils (esp allergic damage)

Kidney U/S for hydronephrosis

Identify and describe the management of those features of the disease that require immediate attention and explain the rationale and mode of action of each therapeutic maneuver

  • Hyperkalemia
    • Calcium gluconate 10%
    • Insulin + Glucose
    • Ventolin inhalation
  • Uremic pericaditis
    • Dialysis

Determine the differential diagnosis and explain the pathology underlying each possibility focusing on pre-renal, renal and postrenal causes of acute kidney injury

Prerenal Intrinsic Postrenal
Na (meq/L) < 20 > 40 > 40
BUN/Cr > 80:1 < 60:1 < 60:1
FeNa < 1% > 2% > 2%
Urine sediment Hyaline casts Brown, granular casts Bland


  • decrease in effective circulating volume:
    • result of true intravascular depletion, decreased effective circulating volume to the kidneys, or agents that impair renal blood flow
    • Intravascular depletion: hemorrhage, vomitting, diarrhea, third spacing, diuretics
    • Reduced cardiac output: cardiogenic shock, CHF, tamponade, huge PE
    • Systemic vasodilation: sepsis, anaphylaxis, antiHTN drugs
    • Renal vasoconstriction: hepatorenal syndrome
    • Medications: NSAIDs, contrast dye, hypercalcemia, tacrolimus, cyclosporine, cocaine
  • Treatment: Fluid boluses or continuous IV fluids, monitor urine output


  • Post-obstructive uropathy
    • Need both urine outflow tracts to be blocked (e.g. 2 ureters, or the urethra)
    • Sudden onset of anuria likely indicate post obstructive uropathy
    • Primary causes: BPH, prostate & cervical cancer, stones, strictures, and retroperitoneal fibrosis
  • Treatment: Bladder catheterization and renal U/S to assess hydronephrosis
    • If patient is also volume contracted, will not have hydronephrosis
  • Monitoring: post-obstructive diuresis, hemorrhagic cystitis

Intrinsic Causes

Condition ATN AIN Acute glomerulonephritis
Casts Brown, muddy WBC RBC

Acute tubular necrosis:

  • Most common cause of AKI in hospitalized patients
  • Three phases:
    • Initiation: renal injury lasting hours - days
    • Maintenance: GFR & Urine output at lowest, lasting days - weeks
    • Recovery: Postacute tubular necrosis diuresis, can still experience uremia and hypovolemia since tubular function not completely restored
  • Pathophysiology: Normal -> loss of brush border -> apoptosis -> Sloughing of BM -> renegeration -> Partial restore of function
  • Ischemic ATN causes:
    • Hypotension of any cause. Causes of pre-renal nephropathy will lead to ATN if not treated
    • Hypovolemic states (hemorrhage, volume depletion from GI/renal losses, burns, fluid sequestration)
    • Low cardiac output states (CHF, myocardiopathy, valvulopathy, arrhythmia, pericardial diseases, tamponade)
    • Systemic vasodilation (sepsis, anaphylaxis)
    • DIC
    • Renal vasoconstriction (cyclosporine, tacrolimus, norepi, epi, amphotericin B)
    • Hyperviscosity syndrome
    • Impaired renal autoregulatory responses caused by COXi
  • Nephrotoxic causes:
    • drugs are the #1 cause
    • Kidneys good target due to rich blood supply, 25% of CO, helps in excretion of these toxins by filtration and secretion
    • Exogenous toxins: Aminoglycosides, contrast dye, cyclosporine & tacrolimus, etc
    • Endogenous toxins:
      • Myoglobinuria (crush injuries, rhabdo)
      • Hemoglobinuria (free Hgb)
      • Crystals (antifreeze)
      • Multiple myeloma (light chains) - usually easily filtered, but if too much can deposit in kidneys
  • Treatment: Supportive ONLY - correct underlying causes, correct fluid and electrolyte balances, dialysis as needed

Acute Interstitial Nephritis:

  • 70% caused by drug hypersensitivity (difficult to pick up, usually asymptomatic)
    • 30% abx: beta-lactams, cipro, sulfa, NSAIDs; allopurinol
  • 15% caused by infection: strep, CMV
  • 8% idiopathic, 6% autoimmune
  • Tubules filled with lymphocytes, causing WBC (lymphocytes & PMN) in tubules
  • Drug hypersensitivity:
    • Not dose dependent
    • Takes weeks after initial exposure, but only 3-5 days after re-exposure
    • Signs:
      • Fever, serum eosinophilia, maculopapular rash
      • Bland sediment or WBC, urine eosinophils
    • Treatment: Remove offending agents, short course of prednisone. Complete recovery usually within one year

Glomerulonephritis (Nephritic syndrome)

  • Criteria:
    • Hematuria (dysmorphic RBC or RBC casts)
    • Proteinuria <3g/day
    • Increased serum creatinine
    • Hypertension
    • Oliguria
  • Most common cause is IgA nephropathy
  • Type 1 (Anti-glomerular basement Membrane Disease)
    • Goodpastures disease (antiglomerular BM ab, can also attack lungs to cause pulmonary hemorrhage)
      • Anti GBM levels
  • Type 2 (Immune complex disease)
    • IgA nephropathy (during or shortly after viral upper respiratory tract infection)
      • IgA levels
    • Postinfectious glomerulonephritis (after strep throat, about 14 days later, will consume complement)
      • ASOT
    • Lupus nephritis
      • ANA & Anti DNA are high, complement levels low
    • Mixed cryoglobulinemia (made in Hep C)
      • Cold antibodies, Hep B surface antigen, Anti-Hep C antibodies
    • Membranoproliferative glomerulonephritis (very rare, associated with chronic conditions)
  • Type 3 (Pauci-Immune/Classical systemic vasculitis disease)
    • Wegener's granolumatosis (attack lung, kidney, skin, recurrent sinusitis, joint pain, petechial skin rashes, pulmonary hemorrhage)
      • c-ANCA
    • Microscopic polyangitis (attack lung, kidney, skin, recurrent sinusitis, joint pain, petechial skin rashes, pulmonary hemorrhage)
      • p-ANCA
    • Churg-Strauss syndrome (attack lung, kidney, skin. Associated with severe asthma, hypereosinophilia)
      • p- & c- ANCA
  • Treatment: high steroids & Cyclophosphamide

Vascular Causes

  • During cardiac catheterization, about 1% of the times will cause atheromatous debris embolizing to: retina, brain, skin, kidneys, or gut
  • diagnosis of exclusion, will not show up on U/S or MRI. Will show up on renal biopsy (rarely done)
  • Treatment is supportive

Rapidly progressing glomerulonephritis (RPGN) - Crescenteric glomerulonephritis

  • Parietal cells that line Bowman capsule spill into Bowman space, leading to very severe inflammation. 90% will end up on dialysis if not treated. Evolves over weeks. ANY glomerulonephritis can progress into this

List the possible long-term complications and describe their management

  • Most common causes of death associated with AKI: sepsis, cardiac, failure, respiratory failure
    • Mortality lower for nonoliguric (>400mL/day) than oliguric patients
  • Acute indications for dialysis (A-E-I-O-U):
    • Acidosis (metabolic)
    • Electrolytes (hyperkalemia)
    • Ingestion of Drugs
    • Overload (fluids)
    • Uremia (encephalopathy, pericaditis, weight loss due to toxins or anorexia)
  • Uremia S/S: caused by excess of urea, creatinine, and other nitrogenous end products in the blood
    • General: Fatigue, weakness, pruritis
    • Mental status change: encephalopathy, seizures, asterixis
    • GI disturbance: anorexia, early satiety, N/V
    • Uremic pericarditis
    • Platelet dysfunction/bleeding (unusual)


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