Epidemiology and pathogenesis of inflammatory bowel disease after kidney transplantation

Post by Master, Doctor Mai Vien Phuong - Department of Examination & Internal Medicine - Vinmec Central Park International General Hospital

Gastrointestinal complications are common after kidney transplantation, and they have a broad clinical spectrum, ranging from diarrhea to post-renal inflammatory bowel disease (IBD). Chronic immunosuppression may increase the risk of post-transplant infection and drug-related injury and may also be responsible for inflammatory bowel disease in immunosuppressed renal transplant recipients.
Distinguishing the different forms of post-transplant colitis is challenging, as most have similar clinical and histological features. Drug-associated colitis is the most common inflammatory bowel disease following renal transplantation, particularly those associated with chronic use of mycophenolate mofetil, whereas new-onset inflammatory bowel disease is rare. This review will explore inflammatory bowel disease after renal transplantation, with particular focus on the various clinical and histological features, attempting to clearly define the appropriate treatment, thereby improving outcomes. patient's end.

Few studies have investigated the incidence of gastrointestinal complications after kidney transplantation. A true incidence is difficult to assess due to heterogeneity in classification and clinical presentation. Clinical manifestations range from diarrhea, which is the most common symptom, to true inflammatory bowel disease, which is largely less common. Furthermore, most studies focus on a small proportion of patients undergoing colonoscopy with a diagnosis of diarrhea, and in most cases the ultimate diagnosis is nonspecific colitis, which is This may underestimate the true prevalence of the disease. New-onset inflammatory bowel disease after solid organ transplantation (SOT) is extremely rare (206 cases/100000): The majority of cases occur in liver transplant recipients, while only a few cases have been reported in transplant recipients. In one review, Wörns et al. reported 44 cases of new-onset inflammatory bowel disease, but only 2 were detected in renal retransplant recipients. A more recent review identified a total of 27 patients with new-onset inflammatory bowel disease (15 patients with UC and 12 patients with Crohn's disease) after kidney transplantation. In a descriptive study of histological features of inflammatory bowel disease in renal transplant recipients, Pittman et al., among 700 renal transplant recipients, identified 51 patients (7.2%) with gastrointestinal symptoms. chemical. Most of them (33%) were ultimately considered to have drug-related colonic injury, mainly MMF colitis, while 11 (22%) developed infectious colitis, mainly due to Infections caused by Clostridium difficile and CMV. Four (8%) of the patients had clinical and histopathologic colitis that showed de novo inflammatory bowel disease. In a cohort of 940 kidney transplant recipients, Dobies et al found inflammatory bowel disease in 7 patients (0.7%). An additional case of new-onset Crohn's disease was recently reported by Motte et al, making a total of 46 new-onset cases with histologically demonstrated inflammatory bowel disease (23 cases of UC and 21 cases of Crohn's disease). , plus 2 cases not otherwise specified) reported to date in renal transplant recipients, including three pediatric patients. In contrast, MMF-associated colitis has a higher incidence, as it is present in 47% of patients undergoing colonoscopy for chronic diarrhea. Post-transplant new-onset inflammatory bowel disease occurs more frequently in men, with a mean age of 35 years. The main presenting symptoms were diarrhea, abdominal pain, and bright red bloody diarrhea, and the median post-transplant time to presentation of inflammatory bowel disease was 4.6 years. In only one patient, inflammatory bowel disease appeared early, within a year of transplantation.

Several hypotheses have been proposed to explain the paradoxical development of new-onset inflammatory bowel disease in kidney transplant recipients. In the non-transplant population, inflammatory bowel disease is generally caused by activation of the immune system against intestinal antigens, which may include the normal gut microbiota. In the renal transplant setting, immunosuppressive therapy may induce dysregulation of the intestinal immune environment, making it susceptible to various insults that may damage the epithelial barrier of the intestinal mucosa, for prolonged exposure to luminal antigens. This exposure can lead to chronic immune stimulation and inflammatory bowel disease, similar to what occurs in non-immunosuppressed individuals who develop Crohn's disease. Furthermore, dysbiosis of the gut microbiota may be responsible for the increased risk of post-transplant diarrhea and gastrointestinal complications. Immunosuppression may increase patient susceptibility to opportunistic infections Immunosuppression may increase patient susceptibility to opportunistic infections, such as CMV, Escherichia coli , Campylobacter or Salmonella infections, can trigger inflammatory bowel disease, as evidenced by the possibility of co-occurring inflammatory bowel disease and gastrointestinal infection. Immunosuppressive drugs themselves may be responsible for the increased susceptibility of the gastrointestinal mucosa. Furthermore, immunosuppressive drugs themselves may be responsible for increased mucosal susceptibility. gastrointestinal. Experimental studies in mice show that interleukin-2 (IL-2) has important inhibitory effects on T cells, and that reduction of IL-2 can induce autoimmune colitis similar to UC . Thus, the widespread use of IL-2 inhibitors such as basiliximab and tacrolimus in the induction and maintenance of posttransplant immunosuppressive therapy may put patients at increased risk of inflammatory bowel disease, whereas Use of azathioprine may exhibit a protective role. However, in the non-transplant population, the use of tacrolimus showed a clinical benefit in the short-term management of inflammatory bowel disease, suggesting that in the transplant population, the pathogenesis of inflammatory bowel disease is novel. Onset is multifactorial and requires a multihit process.
MMF and mycophenolic acid (MPA) frequently induce post-transplant colitis with diarrhea Furthermore, MMF and mycophenolic acid (MPA), are two of the most effective immunosuppressants in kidney transplant recipients, is a frequent cause of post-transplant colitis associated with diarrhea. Exposure to MPA and MMF seems to directly induce local gastrointestinal toxicity, which may ultimately determine apoptotic cell death and cell death injury through cytotoxic or mediated mechanisms. immunity.
Finally, it has been suggested that steroids may have a protective role due to the possibility of late onset of inflammatory bowel disease during post-transplant follow-up, when steroid doses are kept to a minimum. Indeed, some patients presenting with inflammatory bowel disease during the first trimester post-transplant received early steroid withdrawal. Conclusion
New-onset inflammatory bowel disease after kidney transplantation should be part of the differential diagnosis in patients with chronic diarrhea and abdominal pain, even in the absence of a history of previous gastrointestinal disease, along with with infectious causes, drug-related side effects, or other comorbidities. Management of post-transplant inflammatory bowel disease can be challenging due to current use of immunosuppressive therapy, which may increase the risk of infectious complications.

References Gioco R, Corona D, Ekser B, Puzzo L, Inserra G, Pinto F, Schipa C, Privitera F, Veroux P, Veroux M. Gastrointestinal complications after kidney transplantation. World J Gastroenterol 2020; 26(38): 5797-5811 [PMID: 33132635 DOI: 10.3748/wjg.v26.i38.5797]