nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.24884/1561-6274-2010-14-3-58-68nefr-1232Research ArticleЖУРНАЛ В ЖУРНАЛЕ. ВОПРОСЫ ПЕДИАТРИЧЕСКОЙ НЕФРОЛОГИИJOURNAL IN THE JOURNAL. QUESTIONS OF PEDIATRIC NEPHROLOGYАУТОСОМНО-ДОМИНАНТНЫЙ ПОЛИКИСТОЗ ПОЧЕК У ВЗРОСЛЫХ И ДЕТЕЙAUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE IN CHILDREN AND ADULTSАрутюнянС. С.ArutyunyanS. S.

кафедра факультетской педиатрии

СавенковаН. Д.SavenkovaN. D.

кафедра факультетской педиатрии

Санкт-Петербург, ул. Литовская, д. 2.

h.s.s@mail.ruЛарионоваВ. И.LarionovaV. I.

лаборатория молекулярной диагностики с расширенной группой по экогенетике Научно-исследовательского центра

Санкт-Петербургская государственная педиатрическая медицинская академияRussian Federation2010100320101435868Copyright © Арутюнян С.С., Савенкова Н.Д., Ларионова В.И., 20102010Арутюнян С.С., Савенкова Н.Д., Ларионова В.И.Arutyunyan S.S., Savenkova N.D., Larionova V.I.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/1232

Данный обзор является обобщением современных представлений о генетике, механизмах развития, клинике, диагностике аутосомно-доминантного поликистоза почек (АДПП). Представлены количественная и качественная характеристика мутаций в генах, ответственных за развитие заболевания, новейшие критерии УЗИ-диагностики АДПП, препараты для патогенетической терапии АДПП, которые проходят III фазу контролируемых клинических исследований.

This review is a conclusion of up-to-date conceptions about genetics, mechanisms of development, clinical features and diagnostics of autosomal dominant polycystic kidney disease (ADPKD). The quantitative and qualitative description of mutations in causative genes, novel criteria for ultrasound diagnostics of ADPKD and agents for pathogenetic therapy of ADPKD, which are under phase III controlled clinical trials are presented.

аутосомно-доминантный поликистоз почекполицистин 1полицистин 2autosomal dominant polycystic kidney diseasepolycystin 1polycystin 2ReferencesBergmann C, Zerres K. Polycystic Kidney Disease: ADPKD and ARPKD. In:Comprehensive Pediatric Nephrology. Geary DF, Schaefer-Mosby F. eds. Elsevier, 2008;155-178Bergmann C, Zerres K. Polycystic Kidney Disease: ADPKD and ARPKD. In:Comprehensive Pediatric Nephrology. Geary DF, Schaefer-Mosby F. eds. Elsevier, 2008;155-178Dell K,Sweeney WE. Polycystic Kidney Disease. In:Pediatric Nephrology-Sixth editionAvner E.D., Harmon WE , Niaudet P, Yoshikawa N. eds. Springer, 2009; 849-887Dell K,Sweeney WE. Polycystic Kidney Disease. In:Pediatric Nephrology-Sixth editionAvner E.D., Harmon WE , Niaudet P, Yoshikawa N. eds. Springer, 2009; 849-887Somlo S, Guay-Woodford LM. Polycystic Kidney Disease. In: Genetic Diseases of the Kidney. Lifton R, Somlo S, Giebisch G, Donald W.et al: Elsevier 2009; 393-424Somlo S, Guay-Woodford LM. Polycystic Kidney Disease. In: Genetic Diseases of the Kidney. Lifton R, Somlo S, Giebisch G, Donald W.et al: Elsevier 2009; 393-424Wilson PD. Polycystic kidney disease. N Engl J Med 2004; 350:151-164Wilson PD. Polycystic kidney disease. N Engl J Med 2004; 350:151-164Paterson A, Pei Y. A third gene for autosomal dominant polycystic kidney disease? Kidney Int 1998; 54: 1759-1761Paterson A, Pei Y. A third gene for autosomal dominant polycystic kidney disease? Kidney Int 1998; 54: 1759-1761Paterson AD, Wang KR, Lupea D, St George-Hyslop P et al. Recurrent fetal loss associated with bilineal inheritance of type 1 autosomal dominant polycystic kidney disease. Am J Kidney Dis 2002; 40(1):16-20Paterson AD, Wang KR, Lupea D, St George-Hyslop P et al. Recurrent fetal loss associated with bilineal inheritance of type 1 autosomal dominant polycystic kidney disease. Am J Kidney Dis 2002; 40(1):16-20Martin J, Han C, Gordon LA et al. The sequence and analysis of duplication-rich human chromosome 16. Nature 2004; 432: 988-994Martin J, Han C, Gordon LA et al. The sequence and analysis of duplication-rich human chromosome 16. Nature 2004; 432: 988-994Nilius B, Owsianik G, Voets T, Peters JA. Transient receptor potential cation channels in disease. Physiol Rev 2007; 87: 165-217Nilius B, Owsianik G, Voets T, Peters JA. Transient receptor potential cation channels in disease. Physiol Rev 2007; 87: 165-217Huang AL, Chen X, Hoon MA et al. The cells and logic for mammalian sour detection. Nature 2006; 442: 934-938Huang AL, Chen X, Hoon MA et al. The cells and logic for mammalian sour detection. Nature 2006; 442: 934-938Driscoll JA, Bhalla S, Liapis H, Ibricevic A et al. Autosomal dominant polycystic kidney disease is associated with an increased prevalence of radiographic bronchiectasis. Chest 2008;133(5):1181-1198Driscoll JA, Bhalla S, Liapis H, Ibricevic A et al. Autosomal dominant polycystic kidney disease is associated with an increased prevalence of radiographic bronchiectasis. Chest 2008;133(5):1181-1198Scheffers MS, van der BP, Prins F et al. Polycystin-1, the prod-uct of the polycystic kidney disease 1 gene, co-localizes with desmosomes in MDCK cells. Hum Mol Genet 2000; 9: 2743-2750Scheffers MS, van der BP, Prins F et al. Polycystin-1, the prod-uct of the polycystic kidney disease 1 gene, co-localizes with desmosomes in MDCK cells. Hum Mol Genet 2000; 9: 2743-2750Li A, Tian X, Sung SW, Somlo S. Identification of two novel polycystic kidney disease 1-like genes in human and mouse genomes. Genomics 2003; 82: 498-500Li A, Tian X, Sung SW, Somlo S. Identification of two novel polycystic kidney disease 1-like genes in human and mouse genomes. Genomics 2003; 82: 498-500Hidaka S, Konecke V, Osten L et al. PIGEA-14, a novel coiled-coil protein affecting the intracellular distribution of polycystin-2. J Biol Chem 2004; 279:35009-35016Hidaka S, Konecke V, Osten L et al. PIGEA-14, a novel coiled-coil protein affecting the intracellular distribution of polycystin-2. J Biol Chem 2004; 279:35009-35016Reeders ST. Multilocus polycystic disease. Nat Genet 1992;1:235-237Reeders ST. Multilocus polycystic disease. Nat Genet 1992;1:235-237Jiang ST, Chiou YY et al. Defining a link with ADPKD in mice with con-genitally low expression of Pkdl. Am J Pathol 2006;8: 205-220Jiang ST, Chiou YY et al. Defining a link with ADPKD in mice with con-genitally low expression of Pkdl. Am J Pathol 2006;8: 205-220Thivierge C, Kurbegovic A, Couillard M, Guillaume R et al. Overexpression of PKD1 causes polycystic kidney disease. Mol Cell Biol 2006; 26: 1538Thivierge C, Kurbegovic A, Couillard M, Guillaume R et al. Overexpression of PKD1 causes polycystic kidney disease. Mol Cell Biol 2006; 26: 1538Shibazaki S, Yu Z, Nishio S et al. Cyst formation and activation of the extracellular regulated kinase pathway after kidney specific inactivation of Pkdl. Hum Mol Genet 2008; 17: 1505-1516Shibazaki S, Yu Z, Nishio S et al. Cyst formation and activation of the extracellular regulated kinase pathway after kidney specific inactivation of Pkdl. Hum Mol Genet 2008; 17: 1505-1516Hateboer N, van Dijk MA, Bogdanova N, Coto E et al. Comparison of phenotypes of polycystic kidney disease types 1 and 2. Lancet 1999;353: 103-107Hateboer N, van Dijk MA, Bogdanova N, Coto E et al. Comparison of phenotypes of polycystic kidney disease types 1 and 2. Lancet 1999;353: 103-107Torra R, Badenas C, Perez-Oiler L et al. Increased prevalence of polycystic kidney disease type 2 among elderly polycystic patients. Am J Kidney Dis 2000; 36: 728-734Torra R, Badenas C, Perez-Oiler L et al. Increased prevalence of polycystic kidney disease type 2 among elderly polycystic patients. Am J Kidney Dis 2000; 36: 728-734Barua M, Cil O, Paterson AD, Wang K et al. Family history of renal disease severity predicts the mutated gene in ADPKD. J Am Soc Nephrol 2009; 20(8):1833-1838Barua M, Cil O, Paterson AD, Wang K et al. Family history of renal disease severity predicts the mutated gene in ADPKD. J Am Soc Nephrol 2009; 20(8):1833-1838Harris PC, Bae K, Rossetti S et al. Cyst number but not the rate of cystic growth is associated with the mutated gene in ADPKD. J Am Soc Nephrol 2006;17: 3013-3019Harris PC, Bae K, Rossetti S et al. Cyst number but not the rate of cystic growth is associated with the mutated gene in ADPKD. J Am Soc Nephrol 2006;17: 3013-3019Rossetti S, Chauveau D, Kubly V, Slezak J et al. Association of mutation position in polycystic kidney disease 1 (PKD1) gene and development of a vascular phenotype. Lancet 2003; 361:2196-2201Rossetti S, Chauveau D, Kubly V, Slezak J et al. Association of mutation position in polycystic kidney disease 1 (PKD1) gene and development of a vascular phenotype. Lancet 2003; 361:2196-2201Peral B, Ong A, San Millan JL et al. A stable, nonsense mutation associated with a case of infantile onset polycystic kidney disease 1. Hum Mol Genet 1996; 5: 539-542Peral B, Ong A, San Millan JL et al. A stable, nonsense mutation associated with a case of infantile onset polycystic kidney disease 1. Hum Mol Genet 1996; 5: 539-542Tazon-Vega B, Vilardell M, Perez-Oiler L et al. Study of candi-date genes affecting the progression of renal disease in auto-somal dominant polycystic kidney disease type 1. Nephrol Dial Transplant 2007; 22: 1567-1577Tazon-Vega B, Vilardell M, Perez-Oiler L et al. Study of candi-date genes affecting the progression of renal disease in auto-somal dominant polycystic kidney disease type 1. Nephrol Dial Transplant 2007; 22: 1567-1577Belibi FA, Wallace DP, Yamaguchi T, Christensen M et al. The effect of caffeine on renal epithelial cells from patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2002; 13: 2723-2729Belibi FA, Wallace DP, Yamaguchi T, Christensen M et al. The effect of caffeine on renal epithelial cells from patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2002; 13: 2723-2729Wilson PD. Polycystic kidney disease: new understanding in the pathogenesis. Int J Biochem Cell Biol 2004; 36:1868-1873Wilson PD. Polycystic kidney disease: new understanding in the pathogenesis. Int J Biochem Cell Biol 2004; 36:1868-1873Ostrom L, Tang M, Gruss P, Dressler G. Reduced Pax2 gene dosage increases apoptosis and slows the progression of renal cystic disease. Dev Biol 2000; 219(2): 250-258Ostrom L, Tang M, Gruss P, Dressler G. Reduced Pax2 gene dosage increases apoptosis and slows the progression of renal cystic disease. Dev Biol 2000; 219(2): 250-258Grantham JJ. Mechanisms of progression in autosomal dominant polycystic kidney disease. Kidney Int 1997; 63: 93-97Grantham JJ. Mechanisms of progression in autosomal dominant polycystic kidney disease. Kidney Int 1997; 63: 93-97Nakamura T, Ushiyama C et al. Elevation of serum levels of metalloproteinase-1, tissue inhibitor of metalloproteinase-1 and type IV collagen, and plasma levels of metalloproteinase-9 in polycystic kidney disease. Am J Nephrol 2000; 20(1):32-36Nakamura T, Ushiyama C et al. Elevation of serum levels of metalloproteinase-1, tissue inhibitor of metalloproteinase-1 and type IV collagen, and plasma levels of metalloproteinase-9 in polycystic kidney disease. Am J Nephrol 2000; 20(1):32-36Torres VE, Harris PC. Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 2009;76:149-168Torres VE, Harris PC. Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 2009;76:149-168Belibi FA, Edelstein CL. Novel targets for the treatment of autosomal dominant polycystic kidney disease. Expert Opin Investig Drugs 2010;19(3):315-328Belibi FA, Edelstein CL. Novel targets for the treatment of autosomal dominant polycystic kidney disease. Expert Opin Investig Drugs 2010;19(3):315-328Harris PC, Torres VE. Autosomal dominant polycystic disease in GeneClinics: Clinical Genetic Information Recourse [database online]. Copyright. University of Washington, Seattle. Available at http://www.geneclinics.org. Initial Posting: January 10, 2002. Last Revision: June 2, 2009Harris PC, Torres VE. Autosomal dominant polycystic disease in GeneClinics: Clinical Genetic Information Recourse [database online]. Copyright. University of Washington, Seattle. Available at http://www.geneclinics.org. Initial Posting: January 10, 2002. Last Revision: June 2, 2009Nishiura JL, Neves RF, Eloi SR, Cintra SM et al. Evaluation of nephrolithiasis in autosomal dominant polycystic kidney disease patients. Clin J Am Soc Nephrol 2009; (4), 838-844Nishiura JL, Neves RF, Eloi SR, Cintra SM et al. Evaluation of nephrolithiasis in autosomal dominant polycystic kidney disease patients. Clin J Am Soc Nephrol 2009; (4), 838-844Shamshirsaz A, Bekheirnia M et al. Autosomal-dominant polycystic kidney disease in infancy and childhood: progression and outcome. Kidney Int 2005; 68, 2218-2224Shamshirsaz A, Bekheirnia M et al. Autosomal-dominant polycystic kidney disease in infancy and childhood: progression and outcome. Kidney Int 2005; 68, 2218-2224Андреева ЭФ. Клинико-генетическое исследование детей и подростков с поликистозом почек: Автореф. дис. канд. мед. наук. СПбГПМА. Спб., 2008;18Андреева ЭФ. Клинико-генетическое исследование детей и подростков с поликистозом почек: Автореф. дис. канд. мед. наук. СПбГПМА. Спб., 2008;18Ecder T, Schrier R. Cardiovascular abnormalities inautosomaldominant polycystic kidney disease. Nat Rev Nephrol 2009; 5: 221-222Ecder T, Schrier R. Cardiovascular abnormalities inautosomaldominant polycystic kidney disease. Nat Rev Nephrol 2009; 5: 221-222Qian Q, Hunter LW, Du H, Ren Q, Han Y, Sieck GC. Pkd2+/- vascular smooth muscles develop exaggerated vasocontraction in response to phenylephrine stimulation. J Am Soc Nephrol 2007;18(2):485-493Qian Q, Hunter LW, Du H, Ren Q, Han Y, Sieck GC. Pkd2+/- vascular smooth muscles develop exaggerated vasocontraction in response to phenylephrine stimulation. J Am Soc Nephrol 2007;18(2):485-493Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet 2007; 369: 1287-1301Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet 2007; 369: 1287-1301Bae KT, Zhu F, Chapman AB, Torres VE et al. CRISP Consortium; Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: the consortium for radiologic imaging studies of polycystic kidney disease cohort. Clin J Am Soc Nephrol 2006;1: 64-69Bae KT, Zhu F, Chapman AB, Torres VE et al. CRISP Consortium; Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: the consortium for radiologic imaging studies of polycystic kidney disease cohort. Clin J Am Soc Nephrol 2006;1: 64-69Kumar S, Adeva M, King BF, Kamath PS et al. Duodenal diverticulosis in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 2006; 21: 3576-3588Kumar S, Adeva M, King BF, Kamath PS et al. Duodenal diverticulosis in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 2006; 21: 3576-3588Torra R, Sarquella J, Calabia J, Martн J et al. Prevalence of cysts in seminal tract and abnormal semen parameters in patients with autosomal dominant polycystic kidney disease.Clin J Am Soc Nephrol 2008;3(3):790-793Torra R, Sarquella J, Calabia J, Martн J et al. Prevalence of cysts in seminal tract and abnormal semen parameters in patients with autosomal dominant polycystic kidney disease.Clin J Am Soc Nephrol 2008;3(3):790-793Leung GK, Fan YW. Chronic subdural haematoma and arachnoid cyst in autosomal dominant polycystic kidney disease (ADPKD). J Clin Neurosci 2005;12(7):817-819Leung GK, Fan YW. Chronic subdural haematoma and arachnoid cyst in autosomal dominant polycystic kidney disease (ADPKD). J Clin Neurosci 2005;12(7):817-819Савенкова НД. Нефротический синдром при наследственных заболеваниях. В: Савенкова НД, Папаян АВ, ред. Нефротический синдром в практике педиатра. Эскулап, СПб., 1999; 149-150Савенкова НД. Нефротический синдром при наследственных заболеваниях. В: Савенкова НД, Папаян АВ, ред. Нефротический синдром в практике педиатра. Эскулап, СПб., 1999; 149-150Осипов ИБ, Колесникова ИФ. Поликистоз почек у детей (классификация, этиопатогенез, клиника, диагностика, лечебная тактика).Методические рекомендации. ГПМА, СПб., 2000; 22 сОсипов ИБ, Колесникова ИФ. Поликистоз почек у детей (классификация, этиопатогенез, клиника, диагностика, лечебная тактика).Методические рекомендации. ГПМА, СПб., 2000; 22 сPirson Y, Chauveau D, Torres V. Management of cerebral aneurysms in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2002;13: 269-276Pirson Y, Chauveau D, Torres V. Management of cerebral aneurysms in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2002;13: 269-276Lumiaho A, Ikдheimo R, Miettinen R, Niemitukia L et al. Mitral valve prolapse and mitral regurgitation are common in patients with polycystic kidney disease type 1. Am J Kidney Dis 2001; 38(6): 1208-1216Lumiaho A, Ikдheimo R, Miettinen R, Niemitukia L et al. Mitral valve prolapse and mitral regurgitation are common in patients with polycystic kidney disease type 1. Am J Kidney Dis 2001; 38(6): 1208-1216Godela M, Fick-Broshnan, Zung V et al. Progression of autosomal-dominant polycystic kidney diseasein children. Kidney Int 2001; 59: 1654-1662Godela M, Fick-Broshnan, Zung V et al. Progression of autosomal-dominant polycystic kidney diseasein children. Kidney Int 2001; 59: 1654-1662Pei Y, Obaji J, Dupuis A, Paterson A. Unified Criteria for Ultrasonographic Diagnosis of ADPKD. J Am Soc Nephrol 2009; 20: 205-212Pei Y, Obaji J, Dupuis A, Paterson A. Unified Criteria for Ultrasonographic Diagnosis of ADPKD. J Am Soc Nephrol 2009; 20: 205-212Wong H, Vivian L, Weiler G, Filler G. Patients with autosomal dominant polycystic kidney disease hyperfiltrate early in their disease. Am J Kidney Dis 2004;43(4):624-628Wong H, Vivian L, Weiler G, Filler G. Patients with autosomal dominant polycystic kidney disease hyperfiltrate early in their disease. Am J Kidney Dis 2004;43(4):624-628Ravine D, Gibson RN, Walker RG et al. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet 1994; 343: 824-827Ravine D, Gibson RN, Walker RG et al. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet 1994; 343: 824-827Rossetti S, Consugar MB, Chapman AB, Torres VE et al. CRISP Consortium; Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2007; 18: 2143-2160Rossetti S, Consugar MB, Chapman AB, Torres VE et al. CRISP Consortium; Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2007; 18: 2143-2160Consugar MB, Wong WC, Lundquist PA et al. CRISP Consortium; Characterization of large rearrangements associated in autosomal dominant polycystic kidney disease and the PKD1/TSC2contiguous gene syndrome. Kidney Int 2008; 74: 1468-1479Consugar MB, Wong WC, Lundquist PA et al. CRISP Consortium; Characterization of large rearrangements associated in autosomal dominant polycystic kidney disease and the PKD1/TSC2contiguous gene syndrome. Kidney Int 2008; 74: 1468-1479Badani KK, Hemal AK, Menon M. Autosomal dominant polycystic kidney disease and pain – a review of the disease from aetiology, evaluation, past surgical treatment options to current practice. J Postgrad Med 2004;50(3):222-226Badani KK, Hemal AK, Menon M. Autosomal dominant polycystic kidney disease and pain – a review of the disease from aetiology, evaluation, past surgical treatment options to current practice. J Postgrad Med 2004;50(3):222-226Ruggenenti P, Remuzzi A, Ondei P et al. Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease. Kidney Int 2005;68(1):206-216Ruggenenti P, Remuzzi A, Ondei P et al. Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease. Kidney Int 2005;68(1):206-216Van Keimpema L, Nevens F, Vanslembrouck R, van Oijen MG et al. Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. Gastroenterology 2009;137(5):1661-1668Van Keimpema L, Nevens F, Vanslembrouck R, van Oijen MG et al. Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. Gastroenterology 2009;137(5):1661-1668Torres VE. Role of vasopressin antagonists. Clin J Am Soc Nephrol 2008;3(4):1212-1218Torres VE. Role of vasopressin antagonists. Clin J Am Soc Nephrol 2008;3(4):1212-1218Perico N, Antiga L, Caroli A, Ruggenenti P et al. Sirolimus therapy to halt the progression of ADPKD. J Am Soc Nephrol 2010; 21(6):1031-1040Perico N, Antiga L, Caroli A, Ruggenenti P et al. Sirolimus therapy to halt the progression of ADPKD. J Am Soc Nephrol 2010; 21(6):1031-1040Fassett RG, Coombes JS, Packham D, Fairley KF et al. Effect of pravastatin on kidney function and urinary protein excretion in autosomal dominant polycystic kidney disease. Scand J Urol Nephrol 2010; 44(1):56-61Fassett RG, Coombes JS, Packham D, Fairley KF et al. Effect of pravastatin on kidney function and urinary protein excretion in autosomal dominant polycystic kidney disease. Scand J Urol Nephrol 2010; 44(1):56-61

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