{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:30:30Z","timestamp":1780554630896,"version":"3.54.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nephrol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Tacrolimus (TAC) combined with mycophenolate mofetil (MMF) is the immunosuppressive regimen in the majority of solid organ transplant recipients. Gastrointestinal complaints are frequent, which is considered predominantly a side effect of MMF. However, systematic research in this field is lacking. The aim of this study is to systematically investigate the burden of gastrointestinal complaints in TAC-treated kidney transplant recipients with and without MMF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a single-center, open-label, randomized controlled trial, low immunological risk recipients were randomized to either TAC and MMF or to TAC monotherapy from 6 months after kidney transplantation onwards [NTR4672],. They filled in the Gastrointestinal Symptom Rating Scale questionnaire, which covers five dimensions (abdominal pain, reflux, indigestion, constipation, and diarrhea), 6, 12, and 15 months after transplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seventy-nine recipients were randomized and 72 completed all questionnaires (34 TACmono and 38 TAC\/MMF). At baseline, the mean age was 59 years with 72% male, mean BMI 28 kg\/m<jats:sup>2<\/jats:sup>, eGFR 55 ml\/min\/1.73m2, mean daily dose MMF 1200 mg and TAC 5.8 mg, with trough levels of 2.1 mg\/L and 7.4 ug\/L. Six months after transplantation, 75% of recipients reported troublesome symptoms (score \u22653). Diarrhea was the most troublesome (mean 3.3) and discontinuing MMF significantly reduced it (mean \u0394 score between month 6 and 15 TAC\/MMF -0.9 vs. TACmono -1.8, p=0.03). In recipients with troublesome symptoms, abdominal pain (2.7 to 1.8, p=0.003), indigestion (2.8 to 2.3, p=0.012), and reflux (2.9 to 1.7, p=0.007) significantly decreased over time, independent of MMF use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The majority of kidney transplant recipients with TAC and MMF experienced troublesome gastrointestinal symptoms 6 months after transplantation. While constipation remained troublesome, indigestion, abdominal pain, and reflux improved over time by month 15. Diarrhea only improved after discontinuing MMF.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneph.2022.933954","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T06:50:23Z","timestamp":1658213423000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["The Burden of Gastrointestinal Complaints in Kidney Transplant Recipients Using Tacrolimus With and Without Mycophenolate Mofetil: A Randomized Controlled Study"],"prefix":"10.3389","volume":"2","author":[{"given":"Zainab Al","family":"Fatly","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel GH","family":"Betjes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"van Gestel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieken","family":"Verschragen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies E.","family":"de Weerd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000284983.89207.1a","article-title":"Clinicians Underestimate Gastrointestinal Symptoms and Overestimate Quality of Life in Renal Transplant Recipients: A Multinational Survey of Nephrologists","volume":"84","author":"Ekberg","year":"2007","journal-title":"Transplantation"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00147-004-0768-6","article-title":"Long-Term Outcome of Gastrointestinal Complications in Renal Transplant Patients Treated With Mycophenolate Mofetil","volume":"17","author":"Hardinger","year":"2004","journal-title":"Transpl Int"},{"key":"B3","article-title":"Prevalence of Silent Gastrointestinal Complications in Maintenance Renal Transplant Population","volume":"21","author":"Teplitsky","year":"2010","journal-title":"Saudi J Kidney Dis Transplantation"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.2010.01115.x","article-title":"Gastrointestinal Symptoms Impair Quality of Life in Italian Renal Transplant Recipients But are Under-Recognized by Physicians","volume":"23","author":"Ponticelli","year":"2010","journal-title":"Transplant Int"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.2005.00134.x","article-title":"Gastrointestinal Complications in Renal Transplant Recipients","volume":"18","author":"Ponticelli","year":"2005","journal-title":"Transpl Int"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/tid.12674","article-title":"Severe Chronic Norovirus Diarrheal Disease in Transplant Recipients: Clinical Features of an Under-Recognized Syndrome","volume":"19","author":"Avery","year":"2017","journal-title":"Transpl Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V131277","article-title":"Gastrointestinal Complications of Transplant Immunosuppression","volume":"13","author":"Helderman","year":"2002","journal-title":"J Am Soc Nephrol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2007.07.012","article-title":"Quality of Life in Renal Transplant Recipients Following Conversion From Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium","volume":"39","author":"Cofan","year":"2007","journal-title":"Transplant Proc"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2147\/CEG.S81922","article-title":"Impact of Switching From Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium on Gastrointestinal Side Effects in Patients With Autoimmune Disease: A Phase III, Open-Label, Single-Arm, Multicenter Study","volume":"8","author":"Manger","year":"2015","journal-title":"Clin Exp Gastroenterol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199806150-00007","article-title":"A Blinded, Long-Term, Randomized Multicenter Study of Mycophenolate Mofetil in Cadaveric Renal Transplantation: Results at Three Years. 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