Gut mucosa alterations after kidney transplantation: a cross sectional study

Abstract

Background Kidney transplant recipients (KTRs) rely on immunosuppressants like mycophenolate to prevent organ rejection. However, mycophenolate often causes intestinal symptoms and inflammation in various organs, including the skin and the colon. While KTRs have an increased risk for skin cancer, the risk of colorectal cancer is not increased. Elucidating the histological alterations in the colon of KTRs and comparing these changes with known skin alterations would help understand how immunosuppressants influence cancer development and progression. Methods Whole slide images from gut biopsies (Non-transplanted subjects n = 35, KTRs n = 49) were analyzed using the ImageJ and R programming environment. A total of 22,035 epithelial cells, 38,870 interstitial cells, 3465 epithelial cell mitoses, and 7477 endothelial cells, each characterized by multiple microscopy parameters, from a total of 1788 glands were analyzed. The large database was subsequently analyzed to verify the changes of inflammatory milieu in KTRs and in cancer. Results KTRs without colon-cancer showed a significantly higher density of interstitial cells in the colon compared to non-transplanted patients. Moreover, the increase in interstitial cell number was accompanied by subtle modifications in the architecture of the colon glands, without altering the epithelial cell density. We could not identify significant structural modifications in cancer samples between KTRs and non-transplanted patients. Conclusions Our findings demonstrate an increased number of resident interstitial cells in the colon of KTRs, as in other patients treated with mycophenolate. These changes are associated with subtle alterations in the architecture of colon glands. Graphical abstract