nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.24884/1561-6274-2006-10-3-31-37nefr-607Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. CLINICAL INVESTIGATIONSНОВЫЙ СПОСОБ КОРРЕКЦИИ ГИПЕРГОМОЦИСТЕИНЕМИИ У БОЛЬНЫХ, ПОЛУЧАЮЩИХ ЛЕЧЕНИЕ ХРОНИЧЕСКИМ ГЕМОДИАЛИЗОМA NEW METHOD OF CORRECTION OF HYPERHOMOCYSTEINEMIA IN CHRONIC HEMODIALYSIS PATIENTSСмирновА. В.SmirnovA. V.ДобронравовВ. А.DobronravovV. A.ЖлобаА. А.ZhlobaA. A.ГолубевР. В.GolubevR. V.Научно-исследовательский институт нефрологии и отдел биохимии научно-исследовательского центра Санкт-Петербургского госу­дарственного медицинского университета имени академика И.П. ПавловаRussian Federation2006100320061033137Copyright © Смирнов А.В., Добронравов В.А., Жлоба А.А., Голубев Р.В., 20062006Смирнов А.В., Добронравов В.А., Жлоба А.А., Голубев Р.В.Smirnov A.V., Dobronravov V.A., Zhloba A.A., Golubev R.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/607

ЦЕЛЬ ИССЛЕДОВАНИЯ: оценить эффективность применения препарата ДМПС для коррекции гипергомоцистеинемии у больных, получающих лечение хроническим гемодиализом. ПАЦИЕНТЫ И МЕТОДЫ. Проведено 4-недельное открытое контролируемое проспективное исследование по сравнению эффективности монотерапии витаминами группы В и комбинированной терапии препаратом 2,3-димеркаптопропан-1-сульфонат натрия (ДМПС) в сочетании с витаминами группы В в отношении снижения концентрации общего гомоцистеина (Гци) в плазме крови больных, получающих лечение хроническим гемодиализом (ГД). Больным основной группы (n=20) после сеанса ГД с подкожным (n=10) или внутривенным (n=10) введением ДМПС начинали внутривенное введение фолината кальция, а также витаминов В12 и В6. 20 больным контрольной группы проведен только курс витаминов группы В. РЕЗУЛЬТАТЫ. За сеанс стандартного ГД уровень Гци плазмы снижался на 32±8%. Более выраженное снижение Гци на ГД было обнаружено после подкожного (на 56±17%) и внутривенного (на 57±10%) введения ДМПС. Расчетная экскреция Гци составила 62,3±29,2  мкмоль за сеанс стандартного ГД и 224,0±57,0 мкмоль за сеанс ГД с предшествующим подкожным введением ДМПС. 4-недельный курс витаминов группы В привел к снижению уровня Гци в среднем на 43±19% (30,5±12,3 мкмоль/л до курса лечения и 16,0±4,3 мкмоль/л после курса в среднем). Та же схема лечения после однократного подкожного введения ДМПС привела к существенно более значительному снижению (нормализации) Гци плазмы: в среднем  на 65±9%, с 27,4±5,3 мкмоль/л до 9,7±1,8 мкмоль/л.  ЗАКЛЮЧЕНИЕ. Применение препарата ДМПС значительно увеличивает экскрецию Гци в ходе сеанса ГД, приводит к быстрому и существенному снижению уровня Гци плазмы и позволяет улучшить эффект коррекции гипергомоцистеинемии с помощью витаминов группы В.

THE AIM of the investigation was to evaluate the influence of thiol-containing substance DMPS on the reduction of plasma total homocysteine (Hcy) concentration in hemodialysis (HD) patients. PATIENTS AND METHODS. A four-week long open controlled prospective investigation was carried on to compare the effectiveness of monotherapy with group B vitamins and combined therapy with sodium 2,3-dimercapto-1-propanesulfonate (DMPS) in combination with group B vitamins in relation to a decrease of the concentration of total Hcy in blood plasma of chronic HD patients. In the main group patients (n=20) a HD session with a subcutaneous (n=10) or intravenous (n=10) injection of DMPS was followed by an intravenous injection of calcium folinate and vitamins B 12and B 6 . In the control group consisting of 20 patients only a course of group B vitamins was performed. RESULTS. A session of standard HD resulted in a 32± 8% less level of plasma Hcy. A more pronounced decrease of Hcy after HD was observed following a subcutaneous (by 56±17%) and intravenous (by 57±10%) injection of DMPS. The calculated Hcy excretion was 62.3±29.2 мmol for a standard HD session and 224.0±57.0 мmol for the HD session preceded by a subcutaneous injection of DMPS. The 4 week-long course of group B vitamins resulted in a decreased level of Hcy at an average by 43±19% (30.5±12.3 мmol/l before the course of treatment and 16.0±4.3 мmol /l after the course at an average).The same scheme of treatment after a single subcutaneous injection of DMPS resulted in a substantially more considerable reduction (normalization) of plasma Hcy: at an average by 65± 9%, from 27.4±5.3 мmol /l to 9.7±1.8 мmol/l . CONCLUSION. DMPS considerably increases excretion of Hcy during the HD session, results in a rapid and substantially decreased level of plasma Hcy and allows improvement of the effect of correction of hyperhomocysteinemia using group B vitamins.

гемодиализгипергомоцистеинемиялечениеhemodialysishyperhomocysteinemiareatmentReferencesSirrs S, Duncan L, Djurdjev O et al. Homocyst(e)ine and vascular access complications in hemodialysis patients: insights into a complex metabolic relationships. Nephrol Dial Transplant 1999; 14: 738-743Sirrs S, Duncan L, Djurdjev O et al. Homocyst(e)ine and vascular access complications in hemodialysis patients: insights into a complex metabolic relationships. Nephrol Dial Transplant 1999; 14: 738-743Suliman ME, Qureshi AR, Barany P et al. Hyperhomocysteinemia, nutritional status, and cardiovascular disease in hemodialysis patients. Kidney Int 2000; 57: 1727­1735Suliman ME, Qureshi AR, Barany P et al. Hyperhomocysteinemia, nutritional status, and cardiovascular disease in hemodialysis patients. Kidney Int 2000; 57: 1727­1735Mezzano D, Pais E, Aranda E et al. Inflammation, not hyperhomocysteinemia, is related to oxidative stress and hemostatic and endothelial dysfunction in uremia. Kidney Int 2001; 60: 1844-1851Mezzano D, Pais E, Aranda E et al. Inflammation, not hyperhomocysteinemia, is related to oxidative stress and hemostatic and endothelial dysfunction in uremia. Kidney Int 2001; 60: 1844-1851Bayes B, Cruz Pastor M, Bonal J et al. Homocysteine, C-reactive protein, lipid peroxidation and mortality in haemodialysis patients. Nephrol Dial Transplant 2003; 18: 106­112Bayes B, Cruz Pastor M, Bonal J et al. Homocysteine, C-reactive protein, lipid peroxidation and mortality in haemodialysis patients. Nephrol Dial Transplant 2003; 18: 106­112Chauveau P, Chadefaux B, Coude M et al. Hyperhomocysteinemia, a risk factor for atherosclerosis in chronic uremic patients. Kidney Int 1993; 43: S72-S77Chauveau P, Chadefaux B, Coude M et al. Hyperhomocysteinemia, a risk factor for atherosclerosis in chronic uremic patients. Kidney Int 1993; 43: S72-S77Robinson K, Gupta A, Dennis V et al. Hyperhomocysteinemia confers an independent increased risk of atherosclerosis in end-stage renal disease and is closely linked to plasma folate and pyridoxine concentrations. Circulation 1996; 94: 2743-2748Robinson K, Gupta A, Dennis V et al. Hyperhomocysteinemia confers an independent increased risk of atherosclerosis in end-stage renal disease and is closely linked to plasma folate and pyridoxine concentrations. Circulation 1996; 94: 2743-2748Manns BJ, Burgess ED, Hyndman ME et al. Hyperhomocyst(e)inemia and the prevalence of atherosclerotic vascular disease in patients with end-stage renal disease. Am J Kidney Dis 1999; 34: 669-677Manns BJ, Burgess ED, Hyndman ME et al. Hyperhomocyst(e)inemia and the prevalence of atherosclerotic vascular disease in patients with end-stage renal disease. Am J Kidney Dis 1999; 34: 669-677Kunz K, Petitjean P, Lisri M et al. Cardiovascular morbidity and endothelial dysfunction in chronic HD patients: is homocysteine the missing link? Nephrol Dial Transplant 1999; 14: 1934-1942Kunz K, Petitjean P, Lisri M et al. Cardiovascular morbidity and endothelial dysfunction in chronic HD patients: is homocysteine the missing link? Nephrol Dial Transplant 1999; 14: 1934-1942Zoccali C, Mallamaci F. Homocysteine and risk in end-stage renal disease: a matter of context. Kidney Int 2006; 69: 204-206Zoccali C, Mallamaci F. Homocysteine and risk in end-stage renal disease: a matter of context. Kidney Int 2006; 69: 204-206Dennis VW, Robinson K. Homocysteinemia and vascular disease in end-stage renal disease. Kidney Int 1996; 50: S-11-S-17Dennis VW, Robinson K. Homocysteinemia and vascular disease in end-stage renal disease. Kidney Int 1996; 50: S-11-S-17Bostom AG, Lathrop L. Hyperhomocysteinemia in end-stage renal disease: prevalence, etiology, and potential relationship to arteriosclerotic outcomes. Kidney Int 1997; 52:10-20Bostom AG, Lathrop L. Hyperhomocysteinemia in end-stage renal disease: prevalence, etiology, and potential relationship to arteriosclerotic outcomes. Kidney Int 1997; 52:10-20Смирнов АВ, Добронравов ВА, Голубев РВ и др. Распространенность гипергомоцистеинемии в зависимости от стадии хронической болезни почек. Нефрология 2005; 9(2): 48-52Смирнов АВ, Добронравов ВА, Голубев РВ и др. Распространенность гипергомоцистеинемии в зависимости от стадии хронической болезни почек. Нефрология 2005; 9(2): 48-52Bostom AG, Shemin D, Lapane KL et al. High dose B-vitamin treatment of hyperhomocysteinemia in dialysis patients. Kidney Int 1996; 49: 147-152Bostom AG, Shemin D, Lapane KL et al. High dose B-vitamin treatment of hyperhomocysteinemia in dialysis patients. Kidney Int 1996; 49: 147-152Bostom AG, Shemin D, Gohn RY et al. Treatment of hyperhomocysteinemia in hemodialysis patients and renal transplant recipients. Kidney Int 2001; 59: 246-252Bostom AG, Shemin D, Gohn RY et al. Treatment of hyperhomocysteinemia in hemodialysis patients and renal transplant recipients. Kidney Int 2001; 59: 246-252Gonin JM, Nguyen H, Gonin R et al. Controlled trials of very high dose folic acid, vitamins B12 and B6, intravenous folinic acid and serine for treatment of hyperhomocysteinemia in ESRD. J Nephrol 2003; 16: 522-534Gonin JM, Nguyen H, Gonin R et al. Controlled trials of very high dose folic acid, vitamins B12 and B6, intravenous folinic acid and serine for treatment of hyperhomocysteinemia in ESRD. J Nephrol 2003; 16: 522-534Hultberg B, Andersson A, Sterner G. Plasma homocysteine in renal failure. Clin Nephrol 1993; 40: 230-234Hultberg B, Andersson A, Sterner G. Plasma homocysteine in renal failure. Clin Nephrol 1993; 40: 230-234Arnadottir M, Berg AL, Hegbrant J, Hultberg B. Influence of haemodialysis on plasma total homocysteine concentration. Nephrol Dial Transplant 1999; 14: 142-146Arnadottir M, Berg AL, Hegbrant J, Hultberg B. Influence of haemodialysis on plasma total homocysteine concentration. Nephrol Dial Transplant 1999; 14: 142-146De Vriese AS, Langlois M, Bernard D et al. Effect of dialyser membrane pore size on plasma homocysteine levels in haemodialysis patients. Nephrol Dial Transplant 2003; 18: 2596-2600De Vriese AS, Langlois M, Bernard D et al. Effect of dialyser membrane pore size on plasma homocysteine levels in haemodialysis patients. Nephrol Dial Transplant 2003; 18: 2596-2600Massy ZA. Potential strategies to normalize the levels of homocysteine in chronic renal failure patients. Kidney Int 2003; 63 [Suppl. 84]: S134-S136Massy ZA. Potential strategies to normalize the levels of homocysteine in chronic renal failure patients. Kidney Int 2003; 63 [Suppl. 84]: S134-S136Suliman ME, Anderstam B, Lindholm B, Bergstrom J. Total, free, and protein-bound sulphur amino acids in uraemic patients. Nephrol Dial Transplant 1997; 12: 2332-2338Suliman ME, Anderstam B, Lindholm B, Bergstrom J. Total, free, and protein-bound sulphur amino acids in uraemic patients. Nephrol Dial Transplant 1997; 12: 2332-2338Жлоба АА, Иванова СЮ. Изучение свойств и выявление экспрессии рецептора активированного а 2-макроглобулина человека. Клиническая лабораторная диагностика 2002; 4: 7-11Жлоба АА, Иванова СЮ. Изучение свойств и выявление экспрессии рецептора активированного а 2-макроглобулина человека. Клиническая лабораторная диагностика 2002; 4: 7-11Sass JO, Nakanishi T, Sato T et al. S-homocysteinylation of transthyretin is detected in plasma and serum of humans with different types of hyperhomocysteinemia. Biochem Biophys Res Commun 2003; 310: 242-246Sass JO, Nakanishi T, Sato T et al. S-homocysteinylation of transthyretin is detected in plasma and serum of humans with different types of hyperhomocysteinemia. Biochem Biophys Res Commun 2003; 310: 242-246Scholze A, Ringer C, Beige J. et al. Acetylcysteine reduces plasma homocysteine concentration and improves pulse pressure and endothelial function in patients with end stage renal failure. Circulation 2004; 109: 369-374Scholze A, Ringer C, Beige J. et al. Acetylcysteine reduces plasma homocysteine concentration and improves pulse pressure and endothelial function in patients with end stage renal failure. Circulation 2004; 109: 369-374Friedman AN, Bostom AG, Laliberty P et al. The effect of N-acetylcysteine on plasma total homocysteine levels in hemodialysis: a randomized, controlled study. Am J Kidney Dis 2003; 41: 442-446Friedman AN, Bostom AG, Laliberty P et al. The effect of N-acetylcysteine on plasma total homocysteine levels in hemodialysis: a randomized, controlled study. Am J Kidney Dis 2003; 41: 442-446Жлоба АА, Блашко ЭЛ. Определение общего гомоцистеина в плазме крови методом обращеннофазной жидкостной хроматографии с использованием колонок С8 и С18 Ученые записки СПбГМУ им.акад.И.П.Павлова 2004; XI (2): 20-25Жлоба АА, Блашко ЭЛ. Определение общего гомоцистеина в плазме крови методом обращеннофазной жидкостной хроматографии с использованием колонок С8 и С18 Ученые записки СПбГМУ им.акад.И.П.Павлова 2004; XI (2): 20-25Zhloba AA, Blashko EL. Liquid chromatographic determination of total homocysteine in blood plasma with photometric detection. J Chromatogr B Analyt Technol Biomed Life Sci 2004; 800 (1-2): 275-280Zhloba AA, Blashko EL. Liquid chromatographic determination of total homocysteine in blood plasma with photometric detection. J Chromatogr B Analyt Technol Biomed Life Sci 2004; 800 (1-2): 275-280Friedman AN, Bostom AG, Levey AS et al. Plasma total homocysteine levels among patients undergoing nocturnal versus standart hemodialysis. J Am Soc Nephrol 2002; 13: 265­268Friedman AN, Bostom AG, Levey AS et al. Plasma total homocysteine levels among patients undergoing nocturnal versus standart hemodialysis. J Am Soc Nephrol 2002; 13: 265­268Chambers JC, Ueland PM, Obeid OA et al. Improved vascular endothelial function after oral B vitamins: An effect mediated through reduced concentrations of free plasma homocysteine. Circulation 2000; 102(20):2479-2483Chambers JC, Ueland PM, Obeid OA et al. Improved vascular endothelial function after oral B vitamins: An effect mediated through reduced concentrations of free plasma homocysteine. Circulation 2000; 102(20):2479-2483Refsum H, Smith AD, Ueland PM et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 2004; 50: 3-32Refsum H, Smith AD, Ueland PM et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 2004; 50: 3-32House AA, Wells GA, Donnelly JG et al. Randomised trial of high-flux vs low-flux haemodialysis: effects on homocysteine and lipids. Nephrol Dial Transplant 2000; 15: 1029-1034House AA, Wells GA, Donnelly JG et al. Randomised trial of high-flux vs low-flux haemodialysis: effects on homocysteine and lipids. Nephrol Dial Transplant 2000; 15: 1029-1034Guttormsen AB, Ueland PM, Svarstad E, Refsum H. Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure. Kidney Int 1997; 52: 495-502Guttormsen AB, Ueland PM, Svarstad E, Refsum H. Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure. Kidney Int 1997; 52: 495-502Машковский МД. Лекарственные средства; в 2-х тт. Медицина, М., 1994; т.2; 221-222Машковский МД. Лекарственные средства; в 2-х тт. Медицина, М., 1994; т.2; 221-222Hurlbut KM, Maiorino RM, Mayersohn M et al. Determination and metabolism of dithiol chelating agents. XVI: Pharmacokinetics of 2,3-dimercapto-1-propanesulfonate after intravenous administration to human volunteers. J Pharmacol Exp Ther 1994; 268(2): 662-668Hurlbut KM, Maiorino RM, Mayersohn M et al. Determination and metabolism of dithiol chelating agents. XVI: Pharmacokinetics of 2,3-dimercapto-1-propanesulfonate after intravenous administration to human volunteers. J Pharmacol Exp Ther 1994; 268(2): 662-668

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