References

nid

Нефрология и диализ

Nephrology and Dialysis

1680-44222618-9801

Российское диализное общество

nid-1508

Research Article

ОБЗОРЫ И ЛЕКЦИИ

REVIEWS AND LECTURES

Гемолитико-уремический синдром, не ассоциированный с шига-токсином: эпидемиология, классификация, клиника, диагностика, лечение (Обзор литературы. Часть 1)

Non-Shiga toxin-associated hemolytic uremic syndrome: epidemiology, classification, clinical features, diagnostic, and treatment Review. Part 1

Байко

С. В.

Baiko

S. V.

baiko@yandex.ru

Республиканский центр детской нефрологии и диализа, 2-я детская клиническая больница, г. Минск, БеларусьRussian Federation

2007

23062025

94370377

2025

Байко С.В.

Baiko S.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.nephro.ru/jour/article/view/1508

Гемолитико-уремический синдром (ГУС) - это заболевание, включающее неиммунную (Кумбс-отрицательную) гемолитическую анемию, тромбоцитопению и поражение почек [70]. У детей пусковым фактором развития заболевания чаще всего служит Escherichia coli , продуцирующая шига-подобный токсин (Stx), а типичным проявлением заболевания является диарея («Д+» ГУС), часто кровянистого характера. Острая почечная недостаточность наблюдается в 55-70% случаев [79], однако в большинстве случаев (до 70% по различным данным) функция почек восстанавливается [35, 70]. ГУС, не ассоциированный с шига-токсином (non-Stx-HUS), включает гетерогенную группу пациентов, у которых этиологическое значение инфекции, вызванной бактериями, образующими шига-токсин и шига-подобные токсины, было исключено. Эта форма ГУС может носить спорадический или семейный (т. е. заболевание отмечается более чем у одного члена семьи и воздействие Stx исключено) характер. В целом, исход при non-Stx-HUS хуже. До 50% случаев протекает с развитием терминальной почечной недостаточности или необратимого повреждения головного мозга, а смертность в острой фазе заболевания может достигать 25% [11]. Генетические исследования показали, что семейная форма связана с нарушениями в системе регуляторных белков комплемента. Появляются также данные о том, что аналогичные генетические нарушения могут предрасполагать к развитию спорадических случаев non-Stx-HUS.

атипичный гемолитико-уремический синдромсистема комплементаострая почечная недостаточность

References1

Allford S.L., Hunt B.J., Rose P. et al. Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias. Br J Haematol 2003; 120: 556-573.

Artz M.A., Steenbergen E.J., Hoitsma A.J. et al. Renal transplantation in patients with hemolytic uremic syndrome: High rate of recurrence and increased incidence of acute rejections. Transplantation 2003; 76: 821-826.

Barilla-LaBarca M.L., Liszewski M.K., Lambris J.D. et al. Role of membrane cofactor protein (CD46) in regulation of C4b and C3b deposited on cells. J Immunol 2002; 168: 6298-6304.

Berns J.S., Kaplan B.S., Mackow R.C. et al. Inherited hemolytic uremic syndrome in adults. Am J Kidney Dis 1992; 19: 331-334.

Brioschi S., Porrati F., Bresin E. et al. Mutations in membrane cofactor protein in atypical hemolytic uremic syndrome [Abstract]. Presented at the 7th Congress of the Italian Society of Human Genomics, October 13-15, 2004.

Buddles M.R., Donne R.L., Richards A. et al. Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome. Am J Hum Genet 2000; 66: 1721-1722.

Caprioli J., Bettinaglio P., Zipfel P.F. et al. The molecular basis of familial hemolytic uremic syndrome: Mutation analysis of factor H gene reveals a hot spot in short consensus repeat 20. J Am Soc Nephrol 2001; 12: 297-307.

Caprioli J., Castelletti F., Bucchioni S. et al. Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: The C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease. Hum Mol Genet 2003; 12: 3385-3395.

Carreras L., Romero R., Requesens C. et al. Familial hypocomplementemic hemolytic uremic syndrome with HLA-A3, B7 haplotype. JAMA 1981; 245: 602-604.

Clark W.F., Rock G.A., Buskard N. et al. Therapeutic plasma exchange: An update from the Canadian Apheresis Group. Ann Intern Med 1999; 131: 453-462.

Constantinescu A.R., Bitzan M., Weiss L.S. et al. Non-enteropathic hemolytic uremic syndrome: Causes and short-term course. Am J Kidney Dis 2004; 43: 976-982.

Dlott J.S., Danielson C.F., Blue-Hnidy D.E. et al. Drug-induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: A concise review. Ther Apher Dial 2004; 8: 102-111, 2004.

Donne R.L., Abbs I., Barany P. et al. Recurrence of hemolytic uremic syndrome after live related renal transplantation associated with subsequent de novo disease in the donor. Am J Kidney Dis 2002; 40: E22.

Dragon-Durey M.A., Fremeaux-Bacchi V., Loirat C. et al. Heterozygous and homozygous factor H deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: Report and genetic analysis of 16 cases. J Am Soc Nephrol 2004; 15: 787-795.

Dragon-Durey M.-A., Loirat C., Cloarec S. et al. Anti-factor H antibodies associated with atypical hemolytic uremic syndrome. J Am Soc Nephrol 2005; 16: 555-563.

Dundas S., Murphy J., Soutar R.L. et al. Effectiveness of therapeutic plasma exchange in the 1996 Lanarkshire Escherichia coli O157:H7 outbreak. Lancet 1999; 354: 1327-1330.

Endoh M., Yamashina M., Ohi H. et al. Immunohystochemical demonstration of membrane cofactor protein (MCP) of complement in normal and diseased kidney tissues. Clin Exp Immunol 1993; 94: 182-188.

Erickson L.C., Smith W.S., Biswas A.K. et al. Streptococcus pneumoniae-induced hemolytic uremic syndrome: A case for early diagnosis. Pediatr Nephrol 1994; 8: 211-213.

Ferraris J.R., Ramirez J.A., Ruiz S. et al. Shiga toxin-associated hemolytic uremic syndrome: Absence of recurrence after renal transplantation. Pediatr Nephrol 2002; 17: 809-814.

Filler G., Radhakrishnan S., Strain L. et al. Challenges in the management of infantile factor H associated hemolytic uremic syndrome. Pediatr Nephrol 2004; 19: 908-911.

Franco A., Hernandez D., Capdevilla L. et al. De novo hemolytic-uremic syndrome/thrombotic microangiopathy in renal transplant patients receiving calcineurin inhibitors: Role of sirolimus. Transplant Proc 2003; 35: 1764-1766.

Fremeaux-Bacchi V., Dragon-Durey M.A., Blouin J. et al. Complement factor I: A susceptibility gene for atypical haemolytic uraemic syndrome. J Med Genet 2004; 41: e84.

George J.N. The association of pregnancy with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Curr Opin Hematol 2003; 10: 339-344.

Gerber A., Kirchhoff-Moradpour A.H., Obieglo S. et al. Successful (?) therapy of hemolytic-uremic syndrome with factor H abnormality. Pediatr Nephrol 2003; 18: 952-955.

Goodship T.H., Liszewski M.K., Kemp E.J. et al. Mutations in CD46, a complement regulatory protein, predispose to atypical HUS. Trends Mol Med 2004; 10: 226-231.

Granger C.B., Mahaffey K.W., Weaver W.D. et al. Pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to primary percutaneous coronary intervention in acute myocardial infarction: The Complement Inhibition in Myocardial Infarction Treated with Angioplasty (COMMA) trial. Circulation 2003; 108: 1184-1190.

Hall S.M., Glickman M. The British Paediatric Surveillance Unit. Arch Intern Med 1988; 63: 344-346.

Hammar S.P., Bloomer H.A., McCloskey D. Adult hemolytic uremic syndrome with renal arteriolar deposition of IgM and C3. Am J Clin Pathol 1978; 70: 434-439.

Hellwage J., Jokiranta T.S., Friese M.A. et al. Complement C3b/C3d and cell surface polyanions are recognized by overlapping binding sites on the most carboxyl-terminal domain of complement factor H. J Immunol 2002; 169: 6935-6944.

Hillmen P., Hall C., Marsh J.C. et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med 2004; 350: 552-559.

Hollenbeck M., Kutkuhn B., Aul C. et al. Haemolytic-uraemic syndrome and thrombotic-thrombocytopenic purpura in adults: Clinical findings and prognostic factors for death and end-stage renal disease. Nephrol Dial Transplant 1998; 13: 76-81.

Ichida S., Yuzawa Y., Okada H. et al. Localization of the complement regulatory proteins in the normal human kidney. Kidney Int 1994; 46: 89-96.

Johnstone R.W., Loveland B.E., McKenzie I.F. Identification and quantification of complement regulator CD46 on normal human tissues. Immunology 1993; 79: 341-347.

Jozsi M., Manuelian T., Heinen S. et al. Attachment of the soluble complement regulator factor H to cell and tissue surfaces: Relevance for pathology. Hystol Hystopathol 2004; 19: 251-258.

Kaplan B.S., Meyers K.E., Schulman S.L. The pathogenesis and treatment of hemolytic uremic syndrome. J Am Soc Nephrol 1998; 9: 1126-1133.

Kirschfink M. Targeting complement in therapy. Immunol Rev 2001; 180: 177-189.

Landau D., Shalev H., Levy-Finer G. et al. Familial hemolytic uremic syndrome associated with complement factor H deficiency. J Pediatr 2001; 138: 412-417.

Lara P.N. Jr., Coe T.L., Zhou H. et al. Improved survival with plasma exchange in patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Am J Med 1999; 107: 573-579.

Lazar H.L., Bokesch P.M., van Lenta F. et al. Soluble human complement receptor 1 limits ischemic damage in cardiac surgery patients at high risk requiring cardiopulmonary bypass. Circulation 2004; 110 [Suppl 1]: 11274-11279.

Li J.S., Sanders S.P., Perry A.E. et al. Pharmacokinetics and safety of TP10, soluble complement receptor 1, in infants undergoing cardiopulmonary bypass. Am Heart J 2004; 147: 173-180.

Liszewski M.K., Leung M., Cui W. et al. Dissecting sites important for complement regulatory activity in membrane cofactor protein (MCP; CD46). J Biol Chem 2000; 275: 37692-37701.

Lopez E.L., Diaz M., Grinstein S. et al. Hemolytic uremic syndrome and diarrhea in Argentine children: The role of Shiga-like toxins. J Infect Dis 1989; 160: 469-475.

Manuelian T., Hellwage J., Meri S. et al. Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic uremic syndrome. J Clin Invest 2003; 111: 1181-1190.

Matise I., Cornick N.A., Booher S.L. et al. Intervention with Shiga toxin (Stx) antibody after infection by Stx-producing Escherichia coli. J Infect Dis 2001; 183: 347-350.

Miller R.B., Burke B.A., Schmidt W.J. et al. Recurrence of haemolytic-uraemic syndrome in renal transplants: A single-centre report. Nephrol Dial Transplant 1997; 12: 1425-1430.

Morel-Maroger L., Kanfer A., Solez K. et al. Prognostic importance of vascular lesions in acute renal failure with microangiopathic hemolytic anemia (hemolytic-uremic syndrome): Clinicopathologic study in 20 adults. Kidney Int 1979; 15: 548-558.

Mulvey G.L., Marcato P., Kitov P.I. et al. Assessment in mice of the therapeutic potential of tailored, multivalent Shiga toxin carbohydrate ligands. J Infect Dis 2003; 187: 640-649.

Nakanishi I., Moutabarrik A., Hara T. et al. Identification and characterization of membrane cofactor protein (CD46) in the human kidneys. Eur J Immunol 1994; 24: 1529-1535.

Nathanson S., Fremeaux-Bacchi V., Deschenes G. Successful plasma therapy in hemolytic uremic syndrome with factor H deficiency. Pediatr Nephrol 2001; 16: 554-556.

Neumann H.P., Salzmann M., Bohnert-Iwan B. et al. Haemolytic uraemic syndrome and mutations of the factor H gene: A registry-based study of German speaking countries. J Med Genet 2003; 40: 676-681.

Noris M., Brioschi S., Caprioli J. et al. Familial haemolytic uraemic syndrome and an MCP mutation. Lancet 2003; 362: 1542-1547.

Noris M., Ruggenenti P., Perna A. et al. Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: Role of factor H abnormalities. Italian Registry of Familial and Recurrent Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic Purpura. J Am Soc Nephrol 1999; 10: 281-293.

Novak R.W., Martin C.R., Orsini E.N. Hemolytic-uremic syndrome and T-cryptantigen exposure by neuraminidase-producing pneumococci: An emerging problem? Pediatr Pathol 1983; 1: 409-413.

Obrig T.G., Louise C.B., Lingwood C.A. et al. Endothelial heterogeneity in Shiga toxin receptors and responses. J Biol Chem 1993; 268: 15484-15488.

Pangburn M.K. Cutting edge: Localization of the host recognition functions of complement factor H at the carboxyl-terminal: Implications for hemolytic uremic syndrome. J Immunol 2002; 169: 4702-4706.

Paton A.W., Morona R., Paton J.C. A new biological agent for treatment of Shiga toxigenic Escherichia coli infections and dysentery in humans. Nat Med 2000; 6: 265-270.

Perez-Caballero D., Gonzalez-Rubio C., Gallardo M.E. et al. Clustering of missense mutations in the C-terminal region of factor H in atypical hemolytic uremic syndrome. Am J Hum Genet 2001; 68: 478-484.

Pichette V., Querin S., Schurch W. et al. Familial hemolytic-uremic syndrome and homozygous factor H deficiency. Am J Kidney Dis 1994; 24: 936-941.

Pinyon R.A., Paton J.C., Paton A.W. et al. Refinement of a therapeutic Shiga toxin-binding probiotic for human trials. J Infect Dis 2004; 189: 1547-1555.

Raife T., Friedman K.D., Fenwick B. Lepirudin prevents lethal effects of Shiga toxin in a canine model. Thromb Haemost 2004; 92: 387-393.

Remuzzi G., Galbusera M., Salvadori M. et al. Bilateral nephrectomy stopped disease progression in plasma-resistant hemolytic uremic syndrome with neurological signs and coma. Kidney Int 1996; 49: 282-286.

Remuzzi G., Ruggenenti P. The hemolytic uremic syndrome. Kidney Int 1995; 48: 2-19.

Remuzzi G. Is ADAMTS-13 deficiency specific for thrombotic thrombocytopenic purpura? No. J Thromb Haemost 2003; 1: 632-634.

Renaud C., Niaudet P., Gagnadoux M.F. et al. Haemolytic uraemic syndrome: Prognostic factors in children over 3 years of age. Pediatr Nephrol 1995; 9: 24-29.

Reynolds J.C., Agodoa L.Y., Yuan C.M. et al. Thrombotic microangiopathy after renal transplantation in the United States. Am J Kidney Dis 2003; 42: 1058-1068.

Richards A., Kemp E.J., Liszewski M.K. et al. Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome. Proc Natl Acad Sci U S A 2003; 100: 12966-12971.

Rodriguez de Cordoba S., Esparza-Gordillo J., Goicoechea de Jorge E. et al. The human complement factor H: Functional roles, genetic variations and disease associations. Mol Immunol 2004; 41: 355-367.

Rougier N., Kazatchkine M.D., Rougier J.P. et al. Human complement factor H deficiency associated with hemolytic uremic syndrome. J Am Soc Nephrol 1998; 9: 2318-2326.

Ruggenenti P., Galbusera M., Cornejo R.P. et al. Thrombotic thrombocytopenic purpura: Evidence that infusion rather than removal of plasma induces remission of the disease. Am J Kidney Dis 1993; 21: 314-318.

Ruggenenti P., Noris M., Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int 2001; 60: 831-846.

Ruggenenti P. Post-transplant hemolytic-uremic syndrome. Kidney Int 2002; 62: 1093-1104.

Sanchez-Corral P., Gonzalez-Rubio C., Rodriguez de Cordoba S. et al. Functional analysis in serum from atypical hemolytic uremic syndrome patients reveals impaired protection of host cells associated with mutations in factor H. Mol Immunol 2004; 41: 81-84.

Sanchez-Corral P., Perez-Caballero D., Huarte O. et al. Structural and functional characterization of factor H mutations associated with atypical hemolytic uremic syndrome. Am J Hum Genet 2002; 71: 1285-1295.

Scotland S.M., Willshaw G.A., Smith H.R. et al. Properties of strains of Escherichia coli belonging to serogroup O157 with special reference to production of Vero cytotoxins VT1 and VT2. Epidemiol Infect 1987; 99: 613-624.

Stratton J.D., Warwicker P. Successful treatment of factor H-related haemolytic uraemic syndrome. Nephrol Dial Transplant 2002; 17: 684-685.

Stuhlinger W., Kourilsky O., Kanfer A. et al. Haemolytic-uraemic syndrome: Evidence for intravascular C3 activation [Letter]. Lancet 1974; 2: 788-789.

Takahashi M., Taguchi H., Yamaguchi H. et al. The effect of probiotic treatment with Clostridium butyricum on enterohemorrhagic Escherichia coli O157:H7 infection in mice. FEMS Immunol Med Microbiol 2004; 41: 219-226.

Thompson R.A., Winterborn M.H. Hypocomplementaemia due to a genetic deficiency of beta 1H globulin. Clin Exp Immunol 1981; 46: 110-119.

Tonshoff B., Sammet A., Sanden I. et al. Outcome and prognostic determinants in the hemolytic uremic syndrome of children. Nephron 1994; 68: 63-70.

Tostivint I., Mougenot B., Flahault A. et al. Adult haemolytic and uraemic syndrome: Causes and prognostic factors in the last decade. Nephrol Dial Transplant 2002; 17: 1228-1234.

Tsai H.M., Lian E.C. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998; 339: 1585-1594.

Tsai H.M. Deficiency of ADAMTS-13 in thrombotic and thrombocytopenic purpura. J Thromb Haemost 2003; 1: 2038-204, discussion 2040-2035.

Tsai H.M. Is severe deficiency of ADAMTS-13 specific for thrombotic thrombocytopenic purpura? Yes. J Thromb Haemost 2003; 1: 625-631.

Vesely S.K., George J.N., Lammle B. et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: Relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blood 2003; 102: 60-68.

Walport M.J. Complement. First of two parts. N Engl J Med 2001; 344: 1058-1066.

Walport M.J. Complement. Second of two parts. N Engl J Med 2001; 344: 1140-1144.

Warwicker P., Goodship T.H., Donne R.L. et al. Genetic studies into inherited and sporadic hemolytic uremic syndrome. Kidney Int 1998; 53: 836-844.

Zipfel P.F., Skerka C. Complement factor H and related proteins: An expanding family of complement-regulatory proteins? Immunol Today 1994; 15: 121-126.

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