nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное обществоnid-1357Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESПереносимость препаратов микофеноловой кислоты у пациентов с гастроинтестинальными побочными эффектами на поздних сроках после аллотрансплантации почкиTolerance to maintenance therapy with MMF drugs in patients after kidney transplantation with gastro-intestinal adverse effectsСтоляревичЕ. С.StoliarevichE. S.Stolyarevich@yandex.ruВедерниковаР. Н.VedernikovaR. N.noemail@neicon.ruТомилинаН. А.TomilinaN. A.noemail@neicon.ruФГУ НИИ трансплантологии и искусственных органов Росздрава, г. МоскваRussian Federation20072306202592180185Copyright © Столяревич Е.С., Ведерникова Р.Н., Томилина Н.А., 20252025Столяревич Е.С., Ведерникова Р.Н., Томилина Н.А.Stoliarevich E.S., Vedernikova R.N., Tomilina N.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephro.ru/jour/article/view/1357

Гастроинтестинальные побочные эффекты являются частым осложнением терапии препаратами микофеноловой кислоты, что препятствует достижению максимального иммунодепрессивного эффекта. Целью настоящего исследования было оценить выраженность гастроинтестинальных побочных эффектов и связанного с ними качества жизни у реципиентов трупной почки после перевода их с поддерживающей терапии микофенолат мофетилом (ММФ) на майфортик в эквимолярной дозе. С этой целью было выполнено проспективное исследование у 30 пациентов на поздних сроках после АТП, получавших поддерживающую ИСТ преднизолоном ММФ и циклоспорином. Переносимость препаратов так же, как и связанное с ней качество жизни оценивались при помощи соответствующих опросников. Помимо этого оценивалась динамика желудочно-кишечных симптомов и динамика качества жизни после конверсии с ММФ на майфортик. При анализе динамики выраженности желудочно-кишечных побочных эффектов было выявлено статистически значимое улучшение по всем подшкалам: абдоминальная боль (-1,38; p < 0,001), рефлюкс (-1,06; p = 0,00005), диарея (-1,8; p = 0,00026), диспепсия (-1,0; p < 0,000001)) кроме параметров в подшкале запор (0,36; p = 0,3). Сравнение параметров шкалы выраженности гастроинтестинальных симптомов на качество жизни в течение исследования по общему количеству баллов показало статистически значимый рост с 82,3 ± 17,5 баллов (1 неделя наблюдения) до 108,6 ± 15,5 баллов при p = 0,00013 (12 недель наблюдения). В целом 63% пациентов отметили улучшение как желудочно-кишечных симптомов так и качества жизни после конверсии с ММФ на Майфортик. Таким образом перевод реципиентов трупной почки, находящихся на поддерживающей ИСТ с ММФ, на Майфортик привел к значимому уменьшению выраженности гастроинтестинальных побочных эффектов и улучшению качества жизни пациентов после АТП.

The aim of the study was to evaluate the severity of gastrointestinal adverse effects (GAE) and GAE-related quality of life in stable kidney transplant recipients following their conversion from MMF therapy to enteric-coated micophenolate sodium - Myfortic (EC-MPS) administered at an equimolar dose. The prospective study of 30 kidney graft recipients in maintenance immunosuppressive therapy with MMF, cyclosporine and prednisone was performed. All patients completed the Gastrointestinal Symptom Rating Scale (GSRS; higher score indicates increased severity) and Gastrointestinal Quality of Life Index (GIQLI; higher score indicates better GI-specific health-related QoL). Apart from these, long-time changes in gastrointestinal symptoms and in quality of life following the MMF-to-EC-MPS conversion were evaluated with respective questionnaire at Visits 2 and 3. Before conversion, 93% of patients studied had gastrointestinal disturbances. Analyses of gastrointestinal symptoms intensity changes (GSRS) revealed statistically significant improvements on all subscales: abdominal pain (-1,38; p < 0,001), reflux (-1,06; p = 0,00005), diarrhea (-1,8; p = 0,00026), and dyspepsia (-1,0; p < 0,000001). The GAE-related quality of life also improved significantly: from 82,3 ± 17,5 points (at week 1 of observation) to 108,6 ± 15,5 points at 12 weeks (p = 0,00013). By the end of this study, 63% of patients appraised an improvement in their condition as stable and significant. So the conversion of kidney graft recipients from MMF to EC-MPS resulted in a significant reduction of severity of GAE and in better quality of life.

трансплантация почкииммунодепрессивная терапиямикофнолатыгастроинтестинальные побочные эффектыReferencesBudde K., Curtis J., Knoll G. et al. Enteric-coated mycophenolate sodium can be safely administered in maintenance renal transplant patients: results of a 1-year study. Am J Transplant 2003; 4: 237.Budde K., Curtis J., Knoll G. et al. Enteric-coated mycophenolate sodium can be safely administered in maintenance renal transplant patients: results of a 1-year study. Am J Transplant 2003; 4: 237.Budde K., Knoll G., Curtis J. et al. Safety and Efficacy After Conversion From Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium: Results of a 1-Year Extension Study.Budde K., Knoll G., Curtis J. et al. Safety and Efficacy After Conversion From Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium: Results of a 1-Year Extension Study.Bunnapradist S., Lentine K.L., Burroughs T.E. et al. Micophenolate mofetil dose reduction and discontinuations after gastrointestinal complication are associated with renal transplant graft failure. Transplantation 2006; 82: 102-107.Bunnapradist S., Lentine K.L., Burroughs T.E. et al. Micophenolate mofetil dose reduction and discontinuations after gastrointestinal complication are associated with renal transplant graft failure. Transplantation 2006; 82: 102-107.Behrend M. Adverse gastrointestinal effects of mycophenolate mofetil. Aetiology, incidence and management. Drug Saf 2001; 24: 645-663.Behrend M. Adverse gastrointestinal effects of mycophenolate mofetil. Aetiology, incidence and management. Drug Saf 2001; 24: 645-663.Chan L., Malgaonkar S., Walker R. et al. Patient-Reported gastrointestinal symptom burden and health-related quality of life following conversion from mycophenolate mofetil to Enteric-coated mycophenolate sodium. Transplantation 2006; 81 (9): 1290-1297.Chan L., Malgaonkar S., Walker R. et al. Patient-Reported gastrointestinal symptom burden and health-related quality of life following conversion from mycophenolate mofetil to Enteric-coated mycophenolate sodium. Transplantation 2006; 81 (9): 1290-1297.Hale M.D., Nicholls A.J., Bullingham R. et al. The pharmacokinetic-pharmacodynamic relationship for mycophenolate mofetil in renal transplantation. Clin Parmacol Ther 1998; 68: 699.Hale M.D., Nicholls A.J., Bullingham R. et al. The pharmacokinetic-pharmacodynamic relationship for mycophenolate mofetil in renal transplantation. Clin Parmacol Ther 1998; 68: 699.Hardinger K.L., Brennan D.C., Lowell J. et al. Long-term outcome of gastrointestinal complications in renal transplant patients treated with mycophenolate mofetil. Transplant Int 2004; 17: 609-616.Hardinger K.L., Brennan D.C., Lowell J. et al. Long-term outcome of gastrointestinal complications in renal transplant patients treated with mycophenolate mofetil. Transplant Int 2004; 17: 609-616.Jaeschke R., Singer J., Guyatt G.H. et al. Measurement of health status; ascertaining the minimal clinically important difference. Control Clin Trials 1989; 10: 407-415.Jaeschke R., Singer J., Guyatt G.H. et al. Measurement of health status; ascertaining the minimal clinically important difference. Control Clin Trials 1989; 10: 407-415.Knoll G.A., Macdonald I., Khan A. et al. Micophenolate mofetil dose reduction and the risk of acute rejection after renal transplantation J Am Soc Nephrol 2003, 14: 2381-2386.Knoll G.A., Macdonald I., Khan A. et al. Micophenolate mofetil dose reduction and the risk of acute rejection after renal transplantation J Am Soc Nephrol 2003, 14: 2381-2386.Keown P. A blinded, randomized clinical trial of Mycophenolate Mofetil for the prevention of acute rejection in cadaveric renal transplantation (Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group). Transplantation 1996; 61: 1029.Keown P. A blinded, randomized clinical trial of Mycophenolate Mofetil for the prevention of acute rejection in cadaveric renal transplantation (Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group). Transplantation 1996; 61: 1029.Ojo A.O., Meier-Kriesche H.U., Hanson J.A. et al. Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection. Transplantation 2000; 69: 2405-2409.Ojo A.O., Meier-Kriesche H.U., Hanson J.A. et al. Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection. Transplantation 2000; 69: 2405-2409.Pelletier R.P., Akin B., Henry M.L. et al. The impact of mycophenolate mofetil dosing patterns on clinical outcome after renal transplantation. Clin Transplant 2003: 17: 200-205.Pelletier R.P., Akin B., Henry M.L. et al. The impact of mycophenolate mofetil dosing patterns on clinical outcome after renal transplantation. Clin Transplant 2003: 17: 200-205.Salvadori M., Holzer H., Mattos A. et al. Enteric-coated mycophenolate sodium is therapeutically equivalent to micophenolate mofetil in de novo renal transplant recipients Am J Transpl 2003; 4: 231-236.Salvadori M., Holzer H., Mattos A. et al. Enteric-coated mycophenolate sodium is therapeutically equivalent to micophenolate mofetil in de novo renal transplant recipients Am J Transpl 2003; 4: 231-236.Salvadori M. Long-term administration of enteric-coated mycophenolate sodium in kidney transplant patients Trans Proc 2005; 37: 909-911.Salvadori M. Long-term administration of enteric-coated mycophenolate sodium in kidney transplant patients Trans Proc 2005; 37: 909-911.Sollinger H. for the US Renal Transplant Mycophenolate Mofetil Study Group: Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. Transplantation 1995; 60: 225.Sollinger H. for the US Renal Transplant Mycophenolate Mofetil Study Group: Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. Transplantation 1995; 60: 225.Tierce J.C., Porterfield-Baxa J., Petrilla A.A. et al. Impact of micophenolat mofetil(MMF)-related gastrointestinal complication and MMF dose alteration on transplant outcomes and healthcare costs in renal transplant recipients. Clinical Transplantation 2005; 19: 779-784.Tierce J.C., Porterfield-Baxa J., Petrilla A.A. et al. Impact of micophenolat mofetil(MMF)-related gastrointestinal complication and MMF dose alteration on transplant outcomes and healthcare costs in renal transplant recipients. Clinical Transplantation 2005; 19: 779-784.Van Gelder T., Hillbrands L.B., Vanrenterghem Y. et al. A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation.Van Gelder T., Hillbrands L.B., Vanrenterghem Y. et al. A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation.

The authors declare that there are no conflicts of interest present.