Description

• Acute interstitial nephritis (AIN) is an inflammatory response of the kidney involving interstitial edema and, at times, tubular cell damage. It may be an acute reaction or a result of long-term damage.
• System(s) affected: Renal/Urologic, Endocrine/Metabolic, Immunologic
• Synonym(s): Tubulointerstitial nephritis (TIN), Acute interstitial allergic nephritis

Epidemiology

Pediatric Considerations
Children exposed to lead poisoning are more likely to develop nephritis as a young adult:

• TIN with uveitis presents in adolescent females.
• Atherosclerotic or ischemic nephritis is more common in the elderly.

• Interstitial nephritis accounts for 10–15% of kidney disease in the US.
• Analgesic-induced nephritis is 5–6× more common in women.
• Peak incidence in women 60–70 years of age

Geriatric Considerations
The elderly have more severe disease and increased risk of permanent damage.

General Prevention

• Early recognition and prompt discontinuation of offending agents
• Removal of all sources of heavy metals, including ceramics
• Avoid further nephrotoxic substances.

Pathophysiology

• AIN:
  • Delayed drug hypersensitivity reactions
  • May cause acute renal insufficiency
  • Regardless of the severity of the damage to the tubular epithelium, the renal dysfunction generally is reversible, possibly reflecting the regenerative capacity of tubules with a preserved basement membrane.
• Chronic interstitial nephritis (CIN):
  • Follows long-term exposure to offending agents
  • Often found on routine labs or evaluation for hypertension (HTN)
  • Characterized by interstitial scarring, fibrosis, and tubular atrophy, resulting in progressive chronic renal insufficiency
• TIN is sometimes associated with uveitis.

Etiology

• AIN:
  • Hypersensitivity to drugs (70%):
    • Antibiotics: Penicillin, cephalosporins, sulfonamides, rifampin
    • NSAIDs/Analgesics/Cox-2 inhibitors
    • Sulfa-containing diuretics
    • Phenytoin
    • Allopurinol
    • Cimetidine
    • Proton pump inhibitors (omeprazole and lansoprazole)
    • Indinavir
  • Infectious sources include Legionella, Leptospira, streptococcal organisms, cytomegalovirus, Mycoplasma tuberculosis
  • AIN is associated with primary renal infections, such as acute bacterial pyelonephritis, renal tuberculosis, and fungal nephritis.
  • Acute transplant rejection
  • Immunologic: Systemic lupus erythematosus (SLE), Sjögren syndrome, sarcoidosis, Wegener granulomatosis, cryoglobulinemia
  • Idiopathic (isolated or with uveitis)
• CIN:
  • Drugs: Analgesics, lithium, antineoplastics, antibiotics, anticonvulsants, antihypertensives, immunosuppressants, diuretics, Chinese herbal medicines
  • Heavy metals: Lead, cadmium
  • Obstructive: Stones, neoplasm, prostatic hypertrophy
  • Metabolic: Hypercalcemia, hyperoxaluria, chronic hypokalemia, cystinosis
  • Vascular changes: Cholesterol emboli, HTN, sickle hemoglobinopathy, radiation
  • Toxins: Snakebite venom (hemotoxic or myotoxic)
  • Other: Balkan-endemic nephropathy, Epstein-Barr virus

Commonly Associated Conditions

• Alport syndrome
• Medullary cystic disease
• Inflammatory bowel disease
• Multiple myeloma
• Primary biliary cirrhosis