Acute Kidney Injury Causes

Aka: Acute Kidney Injury Causes, Acute Renal Failure Causes, Prerenal Failure Causes, Postrenal Failure Causes, Intrinsic Renal Failure Causes, Infectious Causes of Acute Interstitial Nephritis

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II. Causes: Prerenal Failure (70% of causes)

  1. See Acute Prerenal Failure
  2. See Medication Causes of Prerenal Failure
  3. Mechanism: Decreased renal perfusion
    1. Intravascular volume depletion (e.g. Dehydration, third-spacing)
    2. Decreased arterial pressure (e.g. CHF, Sepsis)
  4. Extracellular fluid loss (Volume depletion)
    1. Burn Injury
    2. Diarrhea
    3. Vomiting
    4. Diuresis (e.g. Diuretics, DKA)
    5. Diaphoresis
    6. Hemorrhage (e.g. Trauma, major upper gastrointestinal Hemorrhage)
  5. Extracellular fluid volume sequestration
    1. Pancreatitis
    2. Muscle crush injury
    3. Systemic vasodilation (e.g. Septic Shock, Neurogenic Shock)
  6. Inadequate Cardiac Output
    1. Severe Congestive Heart Failure
    2. Cardiogenic Shock
  7. Intra-Renal Vasoconstriction
    1. See Medication Causes of Prerenal Failure (e.g. ACE Inhibitors, ARBs, NSAIDS)
    2. Cardiorenal Syndrome
    3. Hepatorenal Syndrome
    4. Abdominal Compartment Syndrome

III. Causes: Intrinsic Renal Failure - Vascular Injury

  1. Afferent arteriolar Vasoconstriction
    1. Results in decreased driving force
    2. Decreased Glomerular filtration
  2. Causes (Microvascular and Macrovascular)
    1. Renal Artery Stenosis
    2. Thromboembolism
    3. Malignant Hypertension
    4. Thrombotic Thrombocytopenic Purpura (TTP)
    5. Hemolytic Uremic Syndrome (HUS)
    6. Vasculitis

IV. Causes: Intrinsic Renal Failure - Glomerulonephritis

  1. See Acute Glomerulonephritis
  2. Associated with Hematuria and Proteinuria
  3. Causes
    1. Hematologic Disorders (e.g. Hemolytic Uremic Syndrome, Thrombotic Thrombocytopenic Purpura)
    2. Systemic Inflammation (e.g. Systemic Lupus Erythematosus, IgA Nephropathy, Henoch-Schonlein Purpura)
    3. Pulmonary-Renal Syndromes (e.g. Granulomatosis with Polyangiitis, Goodpasture Syndrome)

V. Causes: Intrinsic Renal Failure - Acute Interstitial Nephritis

  1. Associated with erythematous maculopapular rash, fever, Arthralgias (30% of cases)
  2. Analogous to an Allergic Reaction within the Kidney
  3. Medication Causes
    1. See Medication Causes of Interstitial Nephritis
    2. See Medication Causes of Acute Tubular Necrosis
    3. Most common cause of Acute Interstitial Nephritis
      1. Acute Interstitial Nephritis typically occurs >2 weeks after drug started
    4. Typically secondary to a Drug Hypersensitivity or other allergic or autoimmune disorder
      1. Example: Penicillins or Cephalosporin Hypersensitivity Reaction
  4. Infectious Causes (5-10% of Acute Interstitial Nephritis causes)
    1. Diphtheria (classic)
    2. Group A beta hemolytic Streptococcus (classic)
    3. Legionella
    4. Yersinia
    5. Staphylococcus or Streptococcus infection
    6. Mycobacterium
    7. Toxoplasmosis
    8. Mycoplasma
    9. Leptospira
    10. Rickettsia
    11. Syphilis
    12. Herpes viruses (e.g. CMV, EBV, HSV)
    13. Human Immunodeficiency Virus (HIV)
    14. Hantavirus
    15. Hepatitis C
    16. Mumps
    17. Candidiasis
    18. Histoplasmosis
  5. Miscellaneous conditions
    1. Glomerulonephritis
    2. Necrotizing Vasculitis
    3. Systemic Lupus Erythematosus
    4. Acute kidney Transplant Rejection
    5. Sarcoidosis

VI. Causes: Intrinsic Renal Failure - Tubular Injury

  1. See Acute Tubular Necrosis
  2. Most common cause of intrinsic Acute Renal Failure cases
  3. Final common pathway of Kidney injury resulting in cell death and necrosis (analogous to ARDS)
  4. Mechanism
    1. Tubules injured in most but not all acute failure
      1. Renal ischemia (hypoperfusion with <500 ml urine/day)
        1. Trauma with Hemorrhage (common)
        2. Sepsis (common)
        3. Cardiac Arrest
        4. Interrupted renal Blood Flow during surgery
      2. Toxins: Nephrotoxic Drugs, pigmenturia and crystals (typically not oliguric)
        1. See Medication Causes of Acute Tubular Necrosis
        2. Rhabdomyolysis
        3. Intravascular Hemolysis
        4. Calcium Phosphate precipitation
        5. Uric Acid crystals
        6. Tumor Lysis Syndrome
        7. Multiple Myeloma
    2. Tubular obstruction
      1. Abnormal material inspissates and plugs flow
    3. Back-leak
      1. Tubular cells loose integrity
      2. Back-leaks ultrafiltrate
      3. Results in poor waste clearance
  5. Course (3 phases)
    1. Initiation phase (minutes to hours)
      1. Starts with well functioning Kidney
      2. Kidney bombarded by potential toxins
    2. Maintenance phase
      1. Established loss of Renal Function
      2. Kidney unresponsive to simple interventions
    3. Recovery phase (weeks to months)
      1. Complete recovery in Acute Tubular Necrosis

VII. Causes: Postrenal Failure (Renal outflow obstruction)

  1. See Acute Postrenal Failure
  2. Intrarenal (distal tubules)
    1. Nephrolithiasis
    2. Multiple MyelomaProtein
    3. Medications predisposing to Uric Acid crystals (Hyperuricemia, Gout)
      1. See Medication Causes of Postrenal Failure
      2. Includes Methotrexate, Acyclovir, and Protease Inhibitors (e.g. Indinavir or Crixivan)
  3. Extra-Ureteral Obstruction
    1. Prostate Cancer
    2. Bladder Cancer
    3. Cervical Cancer
    4. Retroperitoneal fibrosis
    5. Accidental ureteral ligation during pelvic surgery
  4. Ureteral Obstruction (Bilateral in Renal Failure)
    1. Nephrolithiasis
    2. Thrombosis
    3. Pyogenic debris or sloughed papillae
    4. Edema from retrograde pyelography
  5. Bladder neck obstruction
    1. Benign Prostatic Hypertrophy (BPH)
    2. Neurogenic Bladder
    3. Prostate Cancer
    4. Bladder Cancer
    5. Autonomic Neuropathy
    6. Ganglionic blocking medication
  6. Urethral Obstruction
    1. Urethral valves
    2. Urethral Stricture
  7. Most common causes in children
    1. Neurologic conditions (17%)
    2. Urinary Tract Infection (13%)
    3. Medications (13%)
    4. Local inflammation (7%)
    5. Local invasive cancer (6%)
    6. Benign obstructive causes (6%)
      1. Constipation (13%)
    7. Incarcerated Hernias (2%)
    8. Gatti (2001) J Urol 165(3):918-21 [PubMed]

VIII. Mechanism: Specific Examples

  1. See Intravenous Contrast Related Acute Renal Failure
  2. Renal Ischemia
    1. Tubular obstruction and back-leak
  3. Aminoglycoside Antibiotics
    1. Decreased Glomerular Filtration Rate
    2. Tubular cell injury
  4. Rhabdomyolysis
    1. Decreased afferent Blood Flow
    2. Renal tubular obstruction

IX. Resources

  1. Acute Kidney Injury Guidelines
    1. http://www.renal.org/clinical/guidelinessection/AcuteKidneyInjury.aspx

X. References

  1. Broder (2023) Crit Dec Emerg Med 37(7): 22-3
  2. Mercado (2019) Am Fam Physician 100(11): 687-94 [PubMed]
  3. Meyer (2007) N Engl J Med 357(13): 1316-25 [PubMed]
  4. Rahman (2012) Am Fam Physician 86(7): 631-9 [PubMed]
  5. Singri (2003) JAMA 289(6):747-51 [PubMed]

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