26th June 2023

Acute Interstitial Nephritis

Pathophysiology of Acute interstitial nephritis (AIN)

Acute interstitial nephritis involves damage to the renal interstitium and accounts for approximately twenty-five percent of all drug-induced acute kidney injuries. 85% of the kidney is made up of the interstitium, and it consists of a collection of cells, extracellular matrix, and fluid surrounding the kidney and is essentially the structural support for the tubular architecture and participates in fluid and electrolyte exchange. Injury to renal cells leads to the expression of new antigens, inflammatory cell infiltration and activation of pro-inflammatory cytokines. The infiltrating inflammatory cells, including lymphocytes, macrophages and eosinophils, cause oedema and fibrosis within the interstitium. This can lead to impaired renal function, however, there is minimal or no damage to the glomeruli or blood vessels. The most prevalent cause of acute interstitial nephritis is drug-induced, most commonly secondary to NSAIDs or penicillin. Typical symptoms are fever, rash and arthralgia and other features include hypertension, renal impairment, and eosinophilia.

Causes of AIN

• Drugs
  • Antibiotics – ampicillin, cephalosporins, sulphonamides, penicillin, rifampicin, ciprofloxacin, vancomycin
  • NSAIDs
  • Allopurinol
  • Aciclovir
  • Famotidine
  • Furosemide
  • Omeprazole
  • Phenytoin
• Infections
  • Bacteria – Corynebacterium diphtheriae, campylobacter, legionella, staphylococcus, streptococcus, Mycobacterium tuberculosis
  • Virus – HIV, hantavirus, Epstein-Barr
  • Other – Leptospirosis, Schistosoma
• Systemic diseases
  • Systemic lupus erythematosus
  • Sjogren’s syndrome
  • Sarcoidosis
• Tubulointerstitial nephritis with uveitis (TINU)
  • More prominent in younger age groups and more common in females
  • Presents with fever, weight loss and painful red eyes (often bilateral uveitis)
  • Urinalysis – leukocyturia and proteinuria

Diagnosis

• Urinalysis – proteinuria, leukocytes, occasional white cell casts, eosinophiluria
• Blood tests – signs of acute kidney injury, raised urea, raised creatinine, hyperkalaemia/hypokalaemia, eosinophilia.
• Renal biopsy – gold standard for diagnosis; lymphocytic and plasma cell infiltrates in the peritubular areas of the renal interstitium, normally with associated interstitial oedema.

Management

• Treat the underlying cause, particularly withdrawal of the offending drug, if identified.
• Supportive management of acute kidney injury
• Symptomatic treatment for rash
• Avoid nephrotoxic drugs