Fig 1 from Leeaphorn et al, AJKD

In a recent report published in AJKD, Leeaphorn et al described a patient with multiple medical problems who presented with fever and acute kidney injury and was found to have granulomatous interstitial nephritis (GIN) on kidney biopsy. The patient had an excellent clinical response to mycophenolate mofetil (MMF) therapy. GIN is a rare histologic entity that can be triggered by a list of offending drugs and infectious agents. It can also be part of a systemic disease, especially sarcoidosis. Like most diseases, when a specific etiology cannot be identified, it is labeled Idiopathic GIN. However, as pointed out by the authors, it is hard to completely exclude drugs as a cause and a detailed history that includes both prescribed and over-the-counter medications should be obtained. Another entity to be considered is renal-limited sarcoidosis, which was unlikely in this patient given the normal calcium and angiotensin-converting enzyme levels. Clinical presentation of GIN varies but is usually not associated with heavy proteinuria. In this patient, a kidney biopsy was performed due to a rising creatinine. A subtle but important point to reinforce is the value of the kidney biopsy in unexplained kidney failure, even when the urinalysis is unremarkable. Pathologic findings in idiopathic GIN are nonspecific, and consist of chronic inflammation characterized by focal collections of multinucleated giant cells and varying degrees of interstitial fibrosis and tubular atrophy.

As with any other rare kidney diseases, large prospective clinical trials to guide therapy in this condition are lacking. Treatment with steroids generally helps control the disease, with the potential for relapse once tapered off, as was the case in this patient. MMF has been shown in large trials to be an effective and well-tolerated therapeutic agent for a wide variety of “autoimmune diseases,” especially lupus nephritis. By blocking de novo purine synthesis, MMF inhibits T lymphocyte proliferation; possibly explaining its immunosuppressive effects. The authors report one previous case series describing the successful use of MMF in the treatment of acute interstitial nephritis, but none in patients with idiopathic GIN. In this patient, treatment with MMF and a tapering dose of corticosteroid induced a durable remission for 42 months.

Whether idiopathic GIN should be added as an indication for MMF remains an open question, only to be answered by future studies. In the absence of better evidence, however, cases like this are useful to demonstrate MMF as a potential therapeutic option for this condition.

Abdo Asmar, MD
eAJKD Contributor

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