Acute Interstitial Nephritis

Acute interstitial nephritis (AIN) is an immune mediated inflammatory infiltration of the renal interstitium causing AKI, accounting for 10 to 15% of biopsy proven AKI.

• Drugs (70 to 75%): beta-lactams, proton pump inhibitors, NSAIDs, sulfonamides, fluoroquinolones, rifampicin, allopurinol, 5-ASA, checkpoint inhibitors.
• Infections (5 to 10%): Legionella, leptospirosis, streptococci, CMV, hantavirus, tuberculosis, BK virus in transplants.
• Systemic: sarcoidosis, Sjögren syndrome, SLE, IgG4 related disease, TINU syndrome (tubulointerstitial nephritis with uveitis).
• Mechanism is a type IV (T cell) hypersensitivity, with latency 7 to 10 days (weeks to months for PPIs and NSAIDs).
• Prognosis depends on duration of exposure; delayed withdrawal leads to fibrosis and CKD.

• The classic triad (fever, rash, eosinophilia) occurs in under 10%.
• Non-oliguric AKI, flank pain, malaise, arthralgia.
• NSAID AIN may present with nephrotic range proteinuria.
• Uveitis in TINU, sicca features in Sjögren.
• Hypertension and oedema are uncommon.

• Rising creatinine after a new drug, sterile pyuria, white cell casts, mild proteinuria (under 1 to 2 g/day), haematuria, tubular dysfunction (glycosuria with normal glucose, Fanconi picture, type 4 acidosis).
• Peripheral eosinophilia (30 to 50%); urine eosinophils have poor sensitivity and specificity.
• Ultrasound may show enlarged echogenic kidneys. Gallium scan or PET are not reliable.
• Renal biopsy is the reference standard: interstitial oedema, lymphocytes, plasma cells, eosinophils, tubulitis, with granulomas in some. Perform when the cause is unclear or no improvement after 3 to 5 days of drug withdrawal.
• Check ANA, anti-Ro/La, IgG4, ACE, serum calcium, infection screen.

• Stop the offending drug immediately and avoid rechallenge.
• Supportive care of AKI, with renal replacement therapy if needed.
• Corticosteroids if no improvement within 3 to 7 days or with severe injury or biopsy diagnosis: prednisolone 1 mg/kg (maximum 60 mg) daily for 2 to 4 weeks, then taper over 4 to 6 weeks. Earlier steroid start (within 2 weeks) gives better recovery.
• Steroid sparing or refractory disease: mycophenolate mofetil 1 g twice daily.
• Checkpoint inhibitor AIN: prednisolone 1 mg/kg (grade 2), methylprednisolone 1 to 2 mg/kg (grade 3), with permanent discontinuation in severe cases.
• Treat infection or systemic cause (antibiotics, immunosuppression for IgG4 disease, TINU with topical or systemic steroids for uveitis).
• Cover with PPI is not needed unless it is the culprit; Pneumocystis prophylaxis if prolonged steroids.
• Follow creatinine weekly until stable, then at 3 and 12 months. Up to 40% have residual CKD.