- 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 and cytokines. 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 associated with findings of proteinuria, hematuria, and white cell casts.
- Observed in approximately 20% of patients with AKI or CKD who undergo biopsy
- AIN is the primary cause of 3–4% of patients with ESRD.
- Accounts for 15–20% of AKI
- Peak incidence in women 60 to 70 years of age
- Children with history of lead poisoning are more likely to develop CIN as young adults.
- Tubulointerstitial nephritis with uveitis (TINU) presents in adolescent females with mean age of 15 years.
Elderly (≥65 years) have severe disease and increased risk of permanent damage given polypharmacy, 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%) than younger adults (1)[B].
Etiology and Pathophysiology
- 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].
- Proton pump inhibitors
- Anticancer drugs
- Miscellaneous (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, and HSV, HIV, and 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
- 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
- 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)
- Exposure to heavy metals (e.g., lead, cadmium)
- Renal papillary necrosis
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Domino, Frank J., et al., editors. "Interstitial Nephritis." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2020. www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116840/all/Interstitial_Nephritis.
Interstitial Nephritis. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2020. https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116840/all/Interstitial_Nephritis. Accessed June 10, 2023.
Interstitial Nephritis. (2020). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (27th ed.). Wolters Kluwer. https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116840/all/Interstitial_Nephritis
Interstitial Nephritis [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2020. [cited 2023 June 10]. Available from: https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116840/all/Interstitial_Nephritis.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Interstitial Nephritis ID - 116840 ED - Domino,Frank J, ED - Baldor,Robert A, ED - Golding,Jeremy, ED - Stephens,Mark B, BT - 5-Minute Clinical Consult, Updating UR - https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116840/all/Interstitial_Nephritis PB - Wolters Kluwer ET - 27 DB - 5-Minute Clinical Consult DP - Unbound Medicine ER -