GRANULOMATOUS INTERSTITIAL NEPHRITIS: COULD IT BE TUBERCULOSIS?

Granulomatous interstitial nephritis (GIN) is a rare histologic diagnosis, caused by drugs, infections, auto immune and inflammatory disorders. Drugs and sarcoidosis are found mainly in the Western world while the tuberculous origin is prevalent in India. Tuberculosis is the most common infectious etiology of GIN. While destructive urinary tuberculosis is a well described condition, there has been a growing number of tuberculous GIN of unclear mechanism, without bacteriologic evidence.  

We describe a 28-year-old female patient, a laboratory technician in a mycobacteriology laboratory, with a history of untreated asymptomatic Crohn disease who presented with AKI without proteinuria.  

The patient had a history of Mesalazine and cyclosporine treatment for Crohn disease, stopped for 3 years at the time of the AKI. She took Paracetamol occasionally and denied taking over the counter medication such as non-steroidal anti-inflammatory drugs. She complained of easy bruising, menorrhagia and presented with multiple spontaneous ecchymoses of the legs. The laboratory results on admission were significant for creatinine of 230μmol/l, polyclonal hypogammaglobulinemia and anti-ANA 1/320. The rest of the autoimmune panel was negative, including serum complement, which was not depleted. There were no changes in electrolytes. The ACE was negative. The interferon-gamma release assay (IGRA) was uncertain. The kidney biopsy showed non-necrotizing granulomatous interstitial nephritis. Chest Xray and whole-body PET scanner were negative. Though asymptomatic, Crohn disease was thought to be the cause of the GIN and a TNFα inhibitor was started with 1mg/kg of Prednisolone tapered after 2 months. The creatinine decreased to a plateau of 150µmol/l. Five months after cessation of the corticoids, the patient developed a new episode of AKI without proteinuria. The etiologic tests were repeated and the IGRA came back positive. Anti-TNFα inhibitor antibodies were also found. The eye exam was normal. A second biopsy was performed and found GIN with severe glomerulosclerosis. Ziehl Nielsen, culture and PCR mycobacteria came back negative on the kidney biopsy. The patient received 2 months of anti-tuberculous quadruple therapy then 4 months of double therapy. The corticoids were reintroduced at 1mg/kg a day for a month with progressive tapering over 6 months. The creatinine regressed progressively. Given the work of the patient, a declaration was made for recognition of the probable tuberculous GIN as an occupational disease. At one year after the end of the treatment, the creatinine stays stable at 145µmol/l. 

This case shows multiple confounding factors that could explain the GIN. First, the history of Crohn disease, but asymptomatic at the time of the AKI. Second, the treatment by TNFα inhibitors that could explain the second episode of AKI but didn’t work because of anti-TNF antibodies. Finally, the IGRA, which was initially uncertain, became positive after starting anti-TNF treatment, with further deterioration in renal function. The diagnosis of tuberculosis is presumed given the improvement in renal function after anti-tuberculosis treatment and stability after discontinuation of corticosteroid therapy. 

More studies are needed to explore the mechanisms of tuberculous GIN.