What are the risk factors for intestinal transplant rejection?

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Last updated: June 18, 2025View editorial policy

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From the Guidelines

Risk factors for intestinal transplant rejection include immunological factors, technical complications, patient-related factors, medication non-adherence, and infections, with the most recent and highest quality study suggesting that immunosuppression regimens combining tacrolimus, corticosteroids, and antimetabolites like mycophenolate mofetil are effective in preventing rejection 1.

Key Risk Factors

  • Immunological factors: HLA mismatching between donor and recipient, pre-existing donor-specific antibodies, and previous sensitization through blood transfusions or pregnancies
  • Technical complications: prolonged cold ischemia time (over 9 hours) and surgical complications
  • Patient-related factors: younger recipient age, certain underlying diseases like inflammatory bowel disease, and poor nutritional status pre-transplant
  • Medication non-adherence: inconsistent immunosuppressive therapy allows the immune system to mount a response against the graft
  • Infections: particularly cytomegalovirus (CMV) and Epstein-Barr virus (EBV), can trigger inflammatory responses that promote rejection

Post-Transplant Monitoring and Immunosuppression

  • Frequent endoscopies with biopsies are necessary for monitoring rejection
  • Immunosuppression regimens usually combine tacrolimus, corticosteroids, and antimetabolites like mycophenolate mofetil, with careful therapeutic drug monitoring to maintain appropriate levels 1
  • The introduction of novel immunosuppressive protocols has improved outcomes in intestinal transplantation, with a current 1-year patient survival rate of 92% and a graft survival rate of 89% 1

Important Considerations

  • The intestine's high immunogenicity due to its large lymphoid tissue content and constant exposure to environmental antigens makes it particularly susceptible to rejection compared to other solid organs
  • Infections, particularly CMV and EBV, can resemble rejection clinically and histologically, and therefore require careful diagnosis and management 1

From the Research

Risk Factors for Intestinal Transplant Rejection

The risk factors for intestinal transplant rejection can be categorized into several key areas, including:

  • Patient characteristics: age, underlying medical conditions, and immunosuppression regimen 2
  • Transplant characteristics: type of transplant (e.g. intestinal only vs. multivisceral), inclusion of other organs (e.g. liver), and donor-recipient matching 3, 4
  • Immunological factors: presence of anti-HLA donor specific antibodies (DSA) and calculated panel reactive antibody (cPRA) levels 5

Patient-Related Risk Factors

Some patient-related risk factors for intestinal transplant rejection include:

  • Age: children under 18 years old have a higher incidence of bloodstream infections, which may increase the risk of rejection 3
  • Underlying medical conditions: patients with Crohn's disease may have a higher risk of graft failure compared to those without Crohn's disease 4
  • Immunosuppression regimen: tacrolimus time-in-therapeutic range (TAC-TTR) is associated with freedom from acute rejection and graft failure, with lower TAC-TTR increasing the risk of rejection and graft loss 2

Transplant-Related Risk Factors

Transplant-related risk factors for rejection include:

  • Type of transplant: inclusion of the liver in the transplant may increase the incidence of bloodstream infections, which may increase the risk of rejection 3
  • Donor-recipient matching: higher number of HLA mismatches may increase the risk of rejection 6

Immunological Risk Factors

Immunological risk factors for rejection include:

  • Presence of anti-HLA DSA: patients with elevated cPRA levels and anti-HLA DSA are at high risk for acute antibody-mediated rejection (AAMR) 5
  • Calculated panel reactive antibody (cPRA) levels: elevated cPRA levels are associated with an increased risk of AAMR 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Six-month incidence of bloodstream infections in intestinal transplant patients.

Transplant infectious disease : an official journal of the Transplantation Society, 2012

Research

Mortality and Rates of Graft Rejection or Failure Following Intestinal Transplantation in Patients With vs Without Crohn's Disease.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2016

Research

Eculizumab Salvage Therapy for Antibody-Mediated Rejection in a Desensitization-Resistant Intestinal Re-Transplant Patient.

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2015

Research

Risk Stratification for Rejection and Infection after Kidney Transplantation.

Clinical journal of the American Society of Nephrology : CJASN, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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