Interstitial Nephritis



  • Acute and chronic tubulointerstitial diseases result from the interplay of renal cells and inflammatory cells. Injury to renal cells leads to new local antigen expression, inflammatory cell infiltration, and proinflammatory activation. The outcome is acute interstitial nephritis (AIN) or chronic interstitial nephritis (CIN).
  • Central component in AIN is altered tubular function, which precedes decrements in filtration rate.
  • AIN presents as acute kidney injury (AKI) after the use of offending drugs or agents (OFA) and is associated with proteinuria, hematuria, and white cell casts.



  • Accounts for 15–20% of AKI
  • Peak incidence in women 60 to 70 years of age

Pediatric Considerations

  • Children with history of lead poisoning are more likely to develop CIN as young adults.
  • Tubulointerstitial nephritis with uveitis (TINU) presents in adolescent females.

Geriatric Considerations
Compared to younger counterparts, elderly patients (age ≥65 years) tend to develop more severe disease with increased risk of permanent damage, specifically drug-induced AIN (87% vs. 64%), proton pump inhibitor–induced AIN (18% vs. 6%), but less AIN from autoimmune or systemic causes (7% vs. 27%) (1)[B].

Etiology and Pathophysiology

  • AIN
    • T cell activation by an antigen leads to delayed drug hypersensitivity reactions, which leads to interstitial inflammatory infiltrates that damage tubules.
    • Renal dysfunction generally is partially or completely reversible.
    • Hypersensitivity to drugs (75%): not dose dependent; the top three were omeprazole (12%), amoxicillin (8%), and ciprofloxacin (8%) (2)[C]; many implicated; NSAIDs, antibiotics, proton pump inhibitors, diuretics, AEDs, antivirals, anticancer drugs, allopurinol, H2 blockers, diphenylhydantoin, sulfasalazine, and mesalamine
    • Infections (10–15%): streptococci, Legionella, Leptospira, Leishmania, Escherichia coli, Campylobacter, Salmonella, Treponema pallidum, Mycobacterium tuberculosis, Histoplasma, Coccidioides, Toxoplasma, CMV, EBV, HSV, HIV, and perhaps the SARS-CoV-2 (COVID-19) virus (3)
    • Autoimmune (10–15%): sarcoidosis, SLE, Sjögren syndrome, granulomatosis with polyangiitis, cryoglobulinemia
    • Toxins (e.g., snake bite venom)
    • Idiopathic (5–10%): TINU syndrome and anti–tubular basement membrane (anti-TBM) disease
  • CIN
    • Characterized by interstitial scarring, fibrosis, and tubular atrophy, resulting in progressive CKD
    • Follows long-term exposure to OFA (e.g., heavy metals, especially lead)
    • Often found on routine labs
    • Characterized by interstitial scarring, fibrosis, and tubular atrophy, resulting in progressive CKD

General Prevention

  • Early recognition and prompt discontinuation of OFA
  • Avoid nephrotoxic substances.

Commonly Associated Conditions

  • Chronic pyelonephritis
  • Abuse of analgesics
  • Lithium use
  • Gout and gout therapy
  • Immune disorders
  • Malignancy (lymphoma, multiple myeloma)
  • Amyloidosis
  • Exposure to heavy metals (e.g., lead, cadmium)
  • Renal papillary necrosis
  • Uveitis

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