60 y/o. female Dx’d with Crohn’s 2010. Put on Mesalamine. Developed Interstitial nephrites dx’d in 2011. Taken off Mesalamine upon which I went into Crohn’s remission for 2 years. My Creatinine which was up to 1.2 returned to .89. In 2013 Crohn’s returned. I was being treated with Infliximab for Crohn’s and then after the 13th infusion noticed an ammonia taste in my mouth. That was the only symptom. A renal panel drawn prior to the next infusion revealed a Creat. over 3 and GFR of 15, I’d like to know whether you think the following biopsy points to Crohn’s as the cause or Infliximab as the cause of this renal injury. Also, was I more likely to have interstitial nephritis again since I had it previously? Thanks. KIDNEY BIOPSY (NEEDLE) SEVERE ACUTE AND CHRONIC INTERSTITIAL NEPHRITIS, WITH AN ISOLATED NON-NECROTIZING GRANULOMA (SEE NOTE) NO EVIDENCE OF IMMUNE COMPLEX-MEDIATED OR PARAPROTEIN DEPOSITION DISEASE; CRITERIA FOR IgG4 RELATED DISEASE ARE NOT MET IN THIS SAMPLE MODERATE CHRONIC CHANGES OF THE PARENCHYMA, INCLUDING: – GLOBAL GLOMERULOSCLEROSIS (10% OF GLOMERULI) – MODERATE TUBULAR ATROPHY AND INTERSTITIAL FIBROSIS – SEVERE ARTERIAL AND ARTERIOLAR SCLEROSIS NOTE: The biopsy reveals widespread plasma cell-rich interstitial inflammation, with a focal small non-necrotizing granuloma. This type of injury is most commonly related to a hypersensitivity reaction to drugs (sulfonamides, beta-lactam and other antibiotics, anti-viral agents, diuretics, NSAIDs, cimetidine and H2-blockers, and a long list of miscellaneous drugs). Other causes of chronic active interstitial nephritis include severe various infectious processes, metabolic diseases (gout and hyperuricemic conditions), toxic processes (lithium, lead, and other heavy metals), aristolochic acid nephropathy (Chinese herb nephropathy), physical causes (obstruction and radiation injury), and other conditions (Balkan nephropathy, sarcoidosis, “idiopathic” interstitial nephritis). For most of these conditions there are no specific or even characteristic morphological findings, and the disease process can only be diagnosed by correlating the biopsy findings and the history of the use or exposure to certain drugs or substances. There is no evidence of immune complex or paraprotein deposition. IgG4 related disease is unlikely, given the results of immunohistochemistry studies (see results below). MICROSCOPIC DESCRIPTION: Sections of formalin-fixed, paraffin embedded tissue were evaluated using H&E, PAS, JMS, and trichrome stains. An H&E-stained frozen section taken from the tissue allocated for immunofluorescence microscopy and semi-thin toluidine blue-stained epoxy sections of the tissue processed for electron microscopy were also evaluated using light microscopy. The sample consists of 57 glomeruli (LM-48; IF-5; EM-4), of which 6 are globally sclerosed and several glomeruli appear hypoperfused. The non-sclerosed glomeruli are of normal size and reveal normal thickness of the glomerular capillary loops. Significant endocapillary proliferation or cellular crescents are not seen in the glomeruli. The mesangium is not significantly expanded. The interstitium reveals large areas of intense inflammation, associated with mild edema and focal tubulitis. The infiltrates are composed of lymphocytes and many plasma cells, several eosinophils and scattered neutrophils. Isolated foci of Tamm-Horsfall protein inspissation are present in the interstitium. A focal small non-necrotizing granuloma is noted, with epithelioid cells, lymphocytes, and an isolated multinucleated giant cell. In less involved areas, tubules reveal normal cellular details. In inflamed areas, tubules reveal tubulitis and focal degenerative changes. Several tubules also contain necrotic cellular debris. Several PAS-positive hyaline casts are also noted. The sample shows moderate tubular atrophy and interstitial fibrosis. Arteries and arterioles show severe sclerosis. Arterioles also show focal hyaline degeneration. IMMUNOHISTOCHEMISTRY RESULTS: The staining for CD138, IgG4, and IgG were performed using immunoperoxidase technique. Numerous CD138-positive plasma cells were identified, but only isolated cells stain for IgG4. The positive control slide and the patient’s negative non-immune control slide (normal serum) show appropriate reactivity. The immunohistochemical tests performed at Brigham and Women’s Hospital were developed and their performance characteristics determined by the Immunohistochemistry Laboratories in the Department of Pathology at BWH. They have not been cleared or approved by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. IMMUNOFLUORESCENCE MICROSCOPY: KIDNEY BIOPSY #: E15-926 The sections of the sample submitted for immunofluorescence studies were incubated with antibodies specific for the heavy chains of IgG, IgA, and IgM, for kappa and lambda light chains, fibrin, albumin, and complement components C3 and C1q. The sample contains 5 glomeruli. There is 1 globally sclerosed glomerulus. No significant immune deposits are seen in the glomeruli. IgM stain shows dusty reactivity in the background of the tissue; there is also fine granular reactivity for IgM (trace) along the glomerular capillary loops. Dull reactivity with fibrin is noted along the glomerular capillary loops. Tubular basement membranes show focal fine granular deposition of C3 (trace). Tubules contain several intraluminal casts reactive for polyclonal IgA. The interstitium reveals scattered fibrin deposits. Some interstitial inflammatory cells are positive for kappa or lambda light chains. The vessels exhibit focal deposition of C3. There is no difference in reactivity between kappa and lambda light chains in the glomeruli, tubular casts or background of the tissue. The immunofluorescence microscopy tests performed at Brigham and Women’s Hospital were developed and their performance characteristics determined by the Immunohistochemistry Laboratories in the Department of Pathology at BWH. They have not been cleared or approved by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. ELECTRON MICROSCOPY: KIDNEY BIOPSY #: E15-926 Blocks: 1 Block examined: 1 thick section; 1 thin section. The sample submitted for electron microscopy examination contains 3 glomeruli; 2 glomeruli are examined ultrastructurally. The glomerular visceral epithelial cells reveal moderate effacement of their foot processes. The glomerular basement membranes are segmentally attenuated. Morphometric analysis was performed on 105 sites, using orthogonal intercept method. The harmonic mean of the glomerular basement membrane thickness is 274 nm. The subendothelial space of the basement membrane is segmentally expanded by electron-lucent fluffy material in a few capillaries; a new layer of basement membrane material is formed under the displaced endothelium (double contours). The endothelial cells show no significant changes. The mesangium reveals normal cellular elements and a normal amount of matrix. No electron dense deposits are present in the mesangium. CLINICAL DATA: History: A 60-year-old female with Crohn’s disease who presents with AKI. BUN 44, Cr 2.79 (baseline 0.89 in 2/2014; peak 3.24 on 7/18/15), Alb 4.0, HbA1c 5.4, C3 86, C4 15, free kappa LC/lambda LC ratio 2.45, negative hepatitis B/C, negative SPEP, urine sediment WBC 4/hpf, UA blood negative, proteinuria 0.14 g/gCr. tissue submitted: A/1. LM. B/2. IF. C/3. EM.

I am not able to give a medical opinion without performing a complete history and physical examination.  I suggest that you discuss your concerns with your nephrologist.  The biopsy diagnosis appears to be an interstitial nephritis but I’m not sure a specific cause can be assigned based on the kidney biopsy alone.  You must discuss this with your nephrologist.


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