Acute Interstitial Nephritis

Epidemiology

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

Etiology

Drug-Induced (Allergic) Interstitial Nephritis

Anti-Inflammatories

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

Antibiotics

Diuretics

Proton Pump Inhibitors (PPI’s)

  • Omeprazole (Prilosec) (see Omeprazole, [[Omeprazole]])
  • Lansoprazole (Prevacid) (see Lansoprazole, [[Lansoprazole]])

Other

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

Infectious Interstitial Nephritis

Viral

Bacterial

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

Fungal

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

Parasitic

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

Infiltrative Interstitial Nephritis

Vasculitis-Associated Interstitial Nephritis

Other Etiologies of Interstitial Nephritis

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

Physiology

  • Infection-Associated Acute Interstitial Nephritis: in infections such as Leptospirosis/CMV/Streptococcus/Legionellosis, detection of organism-specific antigens and/or DNA has been demonstrated in renal proximal tubule cells in patients with acute interstitial nephritis

Diagnosis


Clinical Manifestations

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, [[Acute Kidney Injury]])
  • Eosinophiluria
  • Gross Hematuria (see Hematuria, [[Hematuria]]): occurs in only 5% of cases
  • Nephrotic Syndrome (see Nephrotic Syndrome, [[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, [[Arthralgias]]): occur in 45% of cases
    • Fever (see Fever, [[Fever]]): occurs in 27% of cases
    • Peripheral Eosinophilia (see Peripheral Eosinophilia, [[Peripheral Eosinophilia]]): occurs in 23% of cases
    • Rash: occurs in 15% of cases
    • Triad of Fever + Peripheral Eosinophilia + Rash: occurs in 10% of cases

Treatment

  • xxx

References

  • The changing profile of acute tubulointerstitial nephritis. Nephrol Dial Transplant. 2004 Jan;19(1):8-11 [MEDLINE]