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- Acute and chronic tubulointerstitial diseases result from the interplay of renal cells and inflammatory cells and their products. Lethal or sublethal injury to renal cells leads to expression of new local antigens, inflammatory cell infiltration, and activation of proinflammatory and chemoattractant cytokines. These cytokines are produced by macrophages and lymphocytes and also by the renal cells (i.e., proximal tubule, vascular endothelial cells, interstitial cells, fibroblasts). The outcome can be acute interstitial nephritis (AIN) or chronic interstitial nephritis (CIN).
- AIN presents as acute kidney injury (AKI) after the use of offending drugs or agents (OFA) and is associated with typical findings of proteinuria, hematuria, and white cell casts. Less frequently, AIN is secondary to infection or systemic diseases (e.g., sarcoidosis, mixed connective tissue disease [MCTD], SLE, Sjögren syndrome).
- System(s) affected: renal/urologic, endocrine/metabolic, immunologic
- Synonym(s): acute interstitial allergic nephritis
- Children with history of lead poisoning are more likely to develop CIN as young adults.
- Tubulointerstitial nephritis with uveitis (TINU) presents in adolescent females.
- AIN and CIN account for 10–15% of kidney disease.
- Peak incidence in women 60 to 70 years of age
The elderly (≥65 years) have more severe disease and increased risk of permanent damage due to their increased use of OFA, specifically more drug-induced AIN (87% vs. 64%), proton-pump inhibitor-induced AIN (18% vs. 6%), but less AIN due to autoimmune or systemic causes (7% vs. 27%) than younger adults (1)[B].
Etiology and Pathophysiology
- Delayed drug hypersensitivity reactions
- Causes AKI
- Renal dysfunction generally is usually partially or completely reversible, possibly reflecting the regenerative capacity of tubules with a preserved basement membrane.
- Hypersensitivity to drugs (75%): not dose dependent. The three top drug causes were omeprazole (12%), amoxicillin (8%), and ciprofloxacin (8%) in a recent case series (2)[C].
- Antibiotics (e.g., penicillins, cephalosporins, sulfonamides, tetracycline, vancomycin, fluoroquinolones, macrolides, TB meds)
- Proton pump inhibitors
- Antivirals (indinavir)
- NSAIDs (all, including Cox-2 inhibitors)
- Diuretics (thiazide, loop, and triamterene)
- Miscellaneous (allopurinol, H2 blockers, diphenylhydantoin, and 5-aminosalicylates such as Azulfidine and mesalamine)
- Infections: Legionella, Leptospira, streptococci, CMV, Mycobacterium tuberculosis (5–10%)
- Autoimmune disorders (e.g., SLE, Sjögren syndrome, sarcoidosis, Wegener granulomatosis, cryoglobulinemia) (10–15%)
- Toxins (e.g., snake bite venom)
- Follows long-term exposure to OFA (e.g., heavy metals, especially lead)
- Often found on routine labs or evaluation for hypertension (HTN)
- Characterized by interstitial scarring, fibrosis, and tubular atrophy, resulting in progressive chronic kidney disease (CKD)
- Early recognition and prompt discontinuation of OFA
- Avoid further 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