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Renal transplant recipients who present with gastrointestinal complaints may have symptoms related to their underlying renal disease or secondary to their immunosuppressive regimen. Immunosuppression increases patients’ risk for infection and medication-induced injury, and a subset of transplant patients develop a form of inflammatory bowel disease (IBD) despite being immunosuppressed. In this study, we present the spectrum of changes in colonic biopsy histology that occur in the postrenal transplant population, with emphasis on the clinical and histologic features that may allow distinction between several common disorders. Over a 15-year period, 51 postrenal transplant patients underwent colonoscopy with biopsy. Eleven (22%) patients had infectious colitis, and 10 of these had biopsy proven acute colitis. Another 17 (33%) patients were determined to have a medication-related injury based on resolution of symptoms following drug cessation. The majority (53%) of these colonic biopsies demonstrated crypt epithelial cell apoptosis and/or architectural distortion, although 41% were histologically normal. Four (8%) patients were ultimately diagnosed with a form of IBD after exclusion of other etiologies; biopsies from these patients demonstrated chronic active colitis or enteritis with plasma cell–rich expansion of the lamina propria and basal lymphoplasmacytosis. The increased prevalence of IBD in this patient cohort (4/700) compared with that reported in the overall North American population (1 to 2/700) is in line with prior studies and is likely related to the therapeutic regimen and associated immune dysregulation that occurs in solid-organ transplant recipients. We demonstrate that a combination of clinical, endoscopic, and histologic features are useful to distinguish among causes of gastrointestinal symptoms in this high risk population.