From the Guidelines
Tubulointerstitial nephritis is primarily caused by medication reactions, with antibiotics, NSAIDs, proton pump inhibitors, and sulfonamides being frequent culprits, as well as infections, autoimmune disorders, and metabolic conditions, as supported by recent studies 1. The most common causes of tubulointerstitial nephritis include:
- Medication reactions, particularly with antibiotics (especially beta-lactams like penicillins and cephalosporins), NSAIDs, proton pump inhibitors, and sulfonamides
- Infections, such as streptococcal infections, viral infections (cytomegalovirus, Epstein-Barr virus), bacterial infections (Legionella, E. coli), and parasitic infections
- Autoimmune disorders, including lupus, Sjögren's syndrome, and sarcoidosis
- Metabolic disorders, such as hyperuricemia, hypercalcemia, and heavy metal exposure According to a recent study published in the Annals of Oncology 1, the incidence of immune-related renal dysfunction is 2%-7%, with acute interstitial nephritis (AIN) being the most common pathology, observed in 80%-90% of patients. Another study published in the Journal of Clinical Oncology 1 found that the median time to onset of renal toxicities is 14 weeks, and presenting symptoms may include urinary frequency, dark cloudy urine, and fluid retention. The pathophysiology of tubulointerstitial nephritis typically involves an inflammatory response with infiltration of immune cells into the kidney tissue, leading to tubular damage and interstitial fibrosis, as described in a study published in Kidney International 1. Prompt identification and removal of the offending agent, particularly medications, is crucial for preventing progression to chronic kidney disease, as emphasized in the study by J. Haanen et al. 1.
From the Research
Causes of Tubulointerstitial Nephritis
- Medications: Drugs are implicated in 70%-90% of biopsy-proved interstitial nephritis, with antibiotics, proton pump inhibitors, nonsteroidal anti-inflammatory agents, and 5-aminosalicylates being the most common offenders 2.
- Infections: Infections can cause tubulointerstitial nephritis, particularly in children 3.
- Autoimmune and systemic diseases: Conditions such as tubulointerstitial nephritis and uveitis (TINU) syndrome, inflammatory bowel disease, and immunoglobulin G4 (IgG4)-associated immune complex multiorgan autoimmune disease (MAD) can cause tubulointerstitial nephritis 4, 5.
- Environmental exposures: Exposure to certain environmental toxins can cause tubulointerstitial nephritis 6.
- Genetic conditions: Certain genetic conditions can increase the risk of developing tubulointerstitial nephritis 3.
- Idiopathic causes: In some cases, the cause of tubulointerstitial nephritis may be unknown or idiopathic 6.
Specific Causes
- Drug-induced acute interstitial nephritis (DI-AIN) is a common cause of tubulointerstitial nephritis, accounting for 0.5%-3% of all kidney biopsies 2.
- TINU syndrome is a rare autoimmune disorder characterized by acute tubulointerstitial nephritis and uveitis, accounting for approximately 2% of all uveitis cases 4.
- Inflammatory bowel disease and IgG4-associated MAD are also associated with an increased risk of developing tubulointerstitial nephritis 5.