Review Question - QID 101268

This presentation is consistent with acute drug-induced tubulointerstitial nephritis (TIN). Acute drug-induced TIN occurs as a combined type I and type IV hypersensitivity reaction 1-2 weeks after administration of certain drugs: Beta-lactam antibiotics (penicillin), rifampin, sulfonamides, NSAIDs, and diuretics. The rifampin component of the standard anti-TB regimen of isoniazid, rifampin, and pyrazinamide is most likely responsible for the onset of symptoms seen in this patient.

Acute drug-induced TIN is associated with sudden onset of fever, oliguria, rash, as well as eosinophilia/eosinophiluria (key clinical finding that is predictive of acute drug-induced TIN) and a BUN:Cr ratio of less than 15. In this disease, the offending drug acts as a hapten to elicit a combined type I/IV hypersensitivity reaction that can manifest 1-2 weeks after initiation of the agent. Typical treatment is to withdraw administration of the drug.

Kodner and Kudrimoti discuss the diagnosis and prognosis of acute interstitial nephritis: “Renal biopsy remains the gold standard for diagnosis, but it may not be required in mild cases or when clinical improvement is rapid after removal of an offending agent or medication. The time until removal of such agents, and renal biopsy findings, provide the best prognostic information for return to baseline renal function.”

Perazella et al. review the various etiologies of acute interstitial nephritis: "Many etiologies of AIN have been recognized--including allergic/drug-induced, infectious, autoimmune/systemic, and idiopathic forms of disease. The most common etiology of AIN is drug-induced disease, which is thought to underlie 60-70% of cases. Multiple agents from many different classes of drugs can cause AIN, and the clinical presentation and laboratory findings vary according to the class of drug involved."

Illustration A demonstrates a renal biopsy with drug-induced acute interstitial nephritis stained with hematoxylin and eosin. There is prominent interstitial inflammation characterized by lymphocytes, eosinophils, and focal plasma cells.

Incorrect answers:
Answer 2-4: All components of the standard anti-TB regimen; however, not as likely to precipitate acute drug-induced TIN (see above list in explanation). While isoniazid, pyrazinamide, and ethambutol have all been documented to cause cases of AIN, rifampin is much more likely to be the offending agent in this setting.
Answer 5: The presence of eosinophilia/eosinophiluria is more consistent with acute drug-induced TIN. Remember that standard therapy for TB often includes directly observed therapy (DOT), which effectively prevents noncompliance.