Cases from the Brigham and Women's Hospital

The Answer
Drug-induced acute granulomatous interstitial nephritis from rifampicin.

The Question

A 42-year-old man was admitted to the hospital for general malaise and a rapidly rising creatinine.  His past medical history is remarkable for pulmonary tuberculosis, treated one year ago with rifampicin and isoniazid. He discontinued the drugs about six month ago. He was seen as an outpatient 10 days ago for persistent productive cough, low-grade fever, and night sweats. A chest x-ray film showed focal consolidations in the right upper lobe with two 2.5cm. cavitations. Cultures were submitted and the patient was restarted on the tuberculostatic protocol. At this time blood chemistries were all within normal limits, except for a slightly elevated WBC count.

One week later he was seen as an outpatient. The laboratory tests obtained at that time showed normal bilirubin, transaminase, and phosphatase levels. His serum creatinine had risen from 0.9 mg/dl one week ago to 3.8 mg/dl.

His urinary sediment was remarkable for numerous WBC, granular casts, occasional RBC, epithelial cells, and trace protein. RBC cast were not detected in several urine samples obtained during his first few days in the hospital.

    

A renal biopsy was performed on the third day.

Questions:

What is the likely clinical diagnosis?

What will the biopsy show?

Explanation/Pathology

Acute interstitial nephritis (AIN) is an important cause of AKI:  ≈15% of patients hospitalized for AKI. Drug-induced interstitial nephritis represents 4% of all cases studied histologically.

Epithelioid and non-caseating giant-cell granulomas are found in some cases, especially those in which acute interstitial nephritis is secondary to drugs. Granulomatous AIN has been described with drugs like fluoroquinolines, clarithromycin, levetiracetam, lamotrigine, and rifampicin. Other reported cases of granulomatous TIN are seen in infections (tuberculosis), Wegener’s granulomatosis and in sarcoidosis.

A: Extensive interstitial inflammation; the glomerulus is spared
B: Cellular detail of the interstitial infiltrate.  Notice several eosinophils.
C: Active inflammation of the tubules epithelium (tubulitis)
D: Granulomaptus inflammation with multinucleated giant cell.