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Abstract: FR-PO1147

Plasma Citrulline and Mycophenolate Mofetil-Induced Enterocyte Toxicity in Renal Transplant Recipients

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Douwes, Rianne M., University Medical Center Groningen, Groningen, The Netherlands, Groningen, Netherlands
  • Said, Mohammad Yusof, University Medical Center Groningen, Groningen, The Netherlands, Groningen, Netherlands
  • Swarte, J.c., University Medical Center Groningen, Groningen, The Netherlands, Groningen, Netherlands
  • Gomes Neto, Antonio Wouter, University Medical Center Groningen, Groningen, The Netherlands, Groningen, Netherlands
  • Tsikas, Dimitrios, Hannover Medical School, Hannover, Germany
  • Navis, Gerjan, University Medical Center Groningen, Groningen, The Netherlands, Groningen, Netherlands
  • Blokzijl, H., University Medical Center Groningen, Groningen, The Netherlands, Groningen, Netherlands
  • Bakker, Stephan J.L., University Medical Center Groningen, Groningen, The Netherlands, Groningen, Netherlands
Background

Citrulline is a non-protein amino acid mainly produced by enterocytes of the small intestine which can be used as a biomarker of functional enterocyte mass. Plasma citrulline is reduced in diseases characterized by enterocyte damage. Diarrhea is a well-known side effect of Mycophenolate Mofetil (MMF), as a consequence of MMF induced gastrointestinal mucosal injury. To prevent complications from severe diarrhea, clinicians often lower MMF dosages or change to other immunosuppressive regimens. We aimed to investigate whether citrulline levels are associated with MMF use in a large cohort of stable renal transplant recipients (RTR).

Methods

Plasma citrulline concentrations were measured in 567 stable RTR with a ≥ 1 year functioning graft, from the TransplantLines Biobank and Cohort study (Clinicaltrial.gov NCT03272841). Citrulline was measured using a validated UHPLC-MS/MS method. MMF through levels were available in 234 RTR and were natural log transformed to obtain a normal distribution. Associations between MMF use, MMF through levels and plasma citrulline concentrations were analyzed using linear regression analyses.

Results

Mean age was 55.5±13.2 years and 392 RTR (69.1%) used MMF. Mean plasma citrulline concentration was 42.1±14.2 µmol/L. In univariable linear regression analyses, MMF use was inversely associated with plasma citrulline (β: -6.8, P<0.001). After adjustment for age, sex and eGFR, MMF use remained significantly associated with lower citrulline levels (β: -4.6, P<0.001). Moreover, among MMF users, through levels were inversely associated with citrulline levels, independent of age, sex and eGFR (β: -2.8, P=0.02).

Conclusion

This study demonstrates that MMF use is associated with lower citrulline levels in RTR potentially related to MMF induced enterocyte toxicity, which may lower systemic citrulline levels. More research is warranted to validate whether citrulline can be used as biomarker of MMF induced enterocyte toxicity in RTR.

Funding

  • Commercial Support