Relative Frequencies of Etiologies

• Drugs: account for 70-75% of acute interstitial nephritis cases
  • Antibiotics: account for 30-49% of drug-associated acute interstitial nephritis cases
• Infections: account for 4-10% of acute interstitial nephritis cases
• Tubulointerstitial Nephritis and Uveitis Syndrome (TINU): accounts for 5-10% of acute interstitial nephritis cases
• Multisystem Diseases (Systemic Lupus Erythematosus, Sjogren’s Syndrome, etc): account for 10-20% of acute interstitial nephritis cases

Drug-Induced (Allergic) Interstitial Nephritis

Anti-Inflammatories

• Antipyrine
• Azathioprine (Imuran) (see Azathioprine)
• Gold (see Gold)
• Interferons (see Interferons)
• Non-Steroidal Anti-Inflammatory Drugs (NSAID’s) (see Non-Steroidal Anti-Inflammatory Drug): including selective COX-2 inhibitors

Antibiotics

• β-Lactam Antibiotics (see β-Lactam Antibiotics)
  • Cephalosporins (see Cephalosporins)
  • Penicillins (see Penicillins)
• Erythromycin (see Erythromycin)
• Ethambutol (see Ethambutol)
• Fluoroquinolones (see Fluoroquinolones): incidence increases with repeated exposures
  • Ciprofloxacin (Cipro) (see Ciprofloxacin): fluoroquinolone most associated with acute interstitial nephritis
• Isoniazid (INH) (see Isoniazid)
• Polymyxin B (see Polymyxin B)
• Rifampin (see Rifampin)
• Sulfonamides (see Sulfonamides,)
  • Sulfamethoxazole-Trimethoprim (Bactrim, Septra) (see Sulfamethoxazole-Trimethoprim)
• Tetracyclines (see Tetracyclines)
• Vancomycin (see Vancomycin)

Diuretics

• Bumetanide (Bumex) (see Bumetanide)
• Chlorthalidone (Hygroton, Tenoretic) (see Chlorthalidone)
• Furosemide (Lasix) (see Furosemide)
• Thiazides (see Thiazides)
  • Chlorothiazide (see Chlorothiazide)
  • Hydrochlorothiazide (HCTZ) (see Hydrochlorothiazide)
• Triamterene (Dyrenium, Dyazide, Maxzide) (see Triamterene)

Proton Pump Inhibitors (PPI’s)

• Omeprazole (Prilosec) (see Omeprazole)
• Lansoprazole (Prevacid) (see Lansoprazole)

Other

• Allopurinol (see Allopurinol)
• α-Methyldopa (see α-Methyldopa)
• Bismuth (see Bismuth)
• Captopril (see Captopril)
• Clofibrate (Atromid-S) (see Clofibrate)
• Coumadin (see Coumadin)
• Etanercept (see Anti-TNF Therapy)
• H2-Histamine Receptor Antagonists (see H2-Histamine Receptor Antagonists)
  • Cimetidine (Tagamet) (see Cimetidine): cimetidine is the H2 blocker most associated with acute interstitial nephritis
  • Ranitidine (Zantac) (see Ranitidine): only rare cases have been reported
• Indinavir (Crixivan) (see Indinavir)
• Mesalamine (see Mesalamine)
• Phenindione
• Phenylpropanolamine (see Phenylpropanolamine)
• Phenytoin (Dilantin) (see Phenytoin)
• Probenecid (see Probenecid)

Infectious Interstitial Nephritis

Viral

• Adenovirus (see Adenovirus)
• Cytomegalovirus (CMV) (see Cytomegalovirus)
• Infectious Mononucleosis (Epstein-Barr Virus) (see Epstein-Barr Virus)
  • Epidemiology
    • Case Report (Clin Infect Dis, 2000) [MEDLINE]
• BK Polyoma Virus (see BK Virus)

Bacterial

• Acute Pyelonephritis (see Urinary Tract Infection)
• Brucellosis (see Brucellosis)
  • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation
• Chlamydia (see Chlamydia)
  • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation
• Diphtheria (see Diphtheria)
• Enterococcus (see Enterococcus)
• Escherichia Coli (see Escherichia Coli)
• Legionellosis (see Legionellosis)
• Leptospirosis (see Leptospirosis)
• Mycoplasma Pneumoniae (see Mycoplasma Pneumoniae)
• Renal Tuberculosis (see Tuberculosis)
  • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation
• Rocky Mountain Spotted Fever (see Rocky Mountain Spotted Fever)
• Staphylococcus (see Staphylococcus)
• Streptococcus (see Streptococcus)
• Syphilis (see Syphilis)
• Tularemia (see Tularemia)
  • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation
• Yersinia (see Yersinia)

Fungal

• Candidiasis (see Candida)
• Coccidioidomycosis (see Coccidioidomycosis)
  • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation
• Histoplasmosis (see Histoplasmosis)
  • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation

Parasitic

• Leishmaniasis (see Leishmaniasis)
  • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation
• Toxoplasmosis (see Toxoplasmosis)
  • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation

Infiltrative Interstitial Nephritis

• Leukemia
• Lymphoma (see Lymphoma)
• Multiple Myeloma (see Multiple Myeloma)
• Sarcoidosis (see Sarcoidosis)

Vasculitis-Associated Interstitial Nephritis

• Churg-Strauss Syndrome (see Churg-Strauss Syndrome)
• Goodpasture’s Syndrome (see Goodpasture’s Syndrome)
• Microscopic Polyangiitis (see Microscopic Polyangiitis)
• Polyarteritis Nodosa (PAN) (see Polyarteritis Nodosa)
• Sjogren’s Syndrome (see Sjogren’s Syndrome)
• Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus)
• Granlomatosis with Polyangiitis (GPA, Wegener’s Granulomatosis) (see Granlomatosis with Polyangiitis)

Other Etiologies of Interstitial Nephritis

• Acute Renal Allograft/Transplant Rejection (see Renal Transplant)
• Immunoglobulin G4-Related Disease (IgG4-Related Disease) (see Immunoglobulin G4-Related Disease)
  • Epidemiology: acute interstitial nephritis is the most common renal manifestation of IgG4-related disease
• Intravenous Drug Abuse (IVDA)
• Radiation Nephritis (see Radiation Therapy)
• Idiopathic Interstitial Nephritis

General Comments

• Asymptomatic Cases: many cases may be asymptomatic
• Latency of Onset in Drug-Induced Acute Interstitial Nephritis: latency typically ranges from 3-5 days to months
  • Rifampin: latency may be as short as 1 day
  • NSAID’s: latency may be as long as 18 mo

Renal Manifestations

• Acute Kidney Injury (AKI) (see Acute Kidney Injury)
• Eosinophiluria
• Gross Hematuria (see Hematuria): occurs in only 5% of cases
• Nephrotic Syndrome (see Nephrotic Syndrome): occurs in <1% of cases
  • However, in NSAID-associated acute interstitial nephritis cases, co-existing membranous nephropathy or minimal change disease may produce nephrotic syndrome
• Oliguria: occurs in 51% of cases

Other Manifestations

Allergic-Type Symptoms

• Epidemiology
  • Although these symptoms have been classically associated with acute interstitial nephritis, they are less commonly-observed in the modern era [MEDLINE]
  • NSAID-related acute interstitial nephritis cases are less associated with these allergic-type symptoms, as compared to other drugs
• Clinical
  • Arthralgias (see Arthralgias): occur in 45% of cases
  • Fever (see Fever): occurs in 27% of cases
  • Peripheral Eosinophilia (see Peripheral Eosinophilia): occurs in 23% of cases
  • Rash: occurs in 15% of cases
  • Triad of Fever + Peripheral Eosinophilia + Rash: occurs in 10% of cases