A. Etiologies

1. Allergic Drug Reactions [2]
   1. Sulfonamide Antibiotics and related compounds (Diuretics, Hypoglycemics)
   2. Methicillin, Penicillin, Ampicillin, Cephalosporins
   3. NSAIDS
   4. Cimetidine (Tagamet®)
2. May be accompanied by rash, fever, abdominal pain
3. Infections - recurrent reflux nephropathy
4. Tubular Obstruction
   1. Crystal Induced - eg. uric acid, calcium phosphate
   2. Inflammatory
   3. "Myelomatous" Kidney
5. Pathology
   1. Tubulointerstitial nephritis may occur with or without glomerulonephritis
   2. Drug reacts are more common without glomerulonephritis
   3. Antibodies to tubular basement membranes have been found
   4. These antibodies are of the IgE or IgG subclasses
   5. In TBM disease with glomerulonephritis, antibodies are against 45-50K tubular antigen

B. Diagnosis

1. Triad of Findings:
   1. Pyuria
   2. Hematuria
   3. White blood cell casts
2. Urinalysis (U/A)
   1. Search for Bence-Jones' Proteins, Crystals, Leukocytes
   2. In typical interstitial nephritis, mild proteinuria is present
   3. Heavy proteinuria is more consistent with glomerular disease
3. Special urine stain for eosinophils - often found in drug reactions
4. Infection must be ruled out: urine Gram stain and culture
5. Biopsy
   1. Plasma Cells and lymphocytes most common
   2. Eosinophils, neutrophils, histiocytes less common
   3. Acute phase generally negative for IgM, IgA, C3 Deposition (IgE or IgG may be found)
6. Renal ultrasound may show enlarged kidneys

C. Treatment

1. Stop medications which may be responsible
2. Adequate fluid hydration with monitoring of renal function
3. Consider moderate dose glucocorticoids for drug reactions (especially with eosinophiluria)
4. Leukotriene inhibition may be beneficial, for example, montelukast (Singulair®) 10-20mg qd
5. Unclear if antihistamines are beneficial, even with IgE mediated disease

References

1. Ambrus JL Jr and Sridhar NR. 1997. JAMA. 278(22):1938
2. Pusey CD, Saltissi D, Bloodworth L, et al. 1983. Quart J Med. 206:194