nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.24884/1561-6274-2010-14-4-9-22nefr-1238Research ArticleПЕРЕДОВАЯ СТАТЬЯLEADING ARTICLEЛЕЧЕНИЕ ГЛОМЕРУЛОПАТИЙ ЦИКЛОСПОРИНОМ: ПРАВИЛЬНЫЙ ПОДХОД С НЕВЕРНЫМ ОБОСНОВАНИЕМGLOMERULOPATHY TREATMENT BY CYCLOSPORINE: THE RIGHT APPROACH WITH THE WRONG RATIONALEСмирновА. В.SmirnovA. V.

кафедра пропедевтики внутренних болезней,

Научно-исследовательский институт нефрологии.

197022, Санкт-Петербург, ул. Л.Толстого, д. 17, СПбГМУ им. акад. И.П. Павлова, корп. 54, кафедра пропедевтики внутренних болезней. Тел.: (812) 234-01-65; Факс: (812) 234-65-30.

smirnov@nephrolog.ruСанкт-Петербургский государственный медицинский университет им. акад. И.П. ПавловаRussian Federation201010042010144922Copyright © Смирнов А.В., 20102010Смирнов А.В.Smirnov A.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/1238

В настоящее время мы являемся свидетелями процесса выхода практической медицины на новый виток своего развития. В мировой медицинской науке создана и набирает силу новая концепция «персонализированной медицины». Основу такой медицины XXI века составляют успехи генетики (фармакогенетики), молекулярной биологии, биохимии, физиологии (экспериментальные исследования). Ярким примером этому может служить почти 30-летняя история изучения вопроса об эффективности применения циклоспорина в лечении нефропатий. Сейчас можно считать доказанным, что циклоспорин действует не только на иммунокомпетентные клетки, но способен восстанавливать сложную структутрно-функциональную организацию подоцитов, существенно повреждающуюся при гломерулопатиях разного генеза. В настоящее время все большее число исследователей склоняются к мысли о том, что при ряде нефропатий (стероидрезистентная болезнь минимальных изменений, мебранозная нефропатия, фокально-сегментарный гломерулосклероз) комбинация циклоспорина с низкими дозами глюкокортикоидов может и должна рассматриваться в качестве терапии первой линии.

Currently, we are witnessing the process practical medicine growing to a new stage in its development. In the world of medical science is created and gaining its strength a new concept of «personalized medicine». On the basis of such medicine lie the 21st century advances in genetics (pharmacogenetics), molecular biology, biochemistry, physiology (experimental studies). A striking example is the nearly 30-year history of research on the effectiveness of cyclosporine in the treatment of nephropathy. It can now be considered proven that cyclosporine acts not only on immunocompetent cells, but is able to restore the complex structural and functional organization of podocytes significantly damaged during glomerulopathies of different genesis. Currently, an increasing number of researchers are inclined to think that in a number of nephropathies (steroid resistant minimal changes disease, mebranous nephropathy, focal segmental glomerulosclerosis) a combination of cyclosporine with low-dose glucocorticoids can and should be treated as first-line therapy.

циклоспоринподоцитыгломерулопатиилечениеcyclosporinepodocytesglomerulopathytreatmentReferencesCattran DC, Alexopoulos E, Heering P et al. Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome: workshop recommendations. Kidney Int 2007; 72 (12): 1429-1447Cattran DC, Alexopoulos E, Heering P et al. Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome: workshop recommendations. Kidney Int 2007; 72 (12): 1429-1447Козловская ЛВ. Хронический гломерулонефрит: аргументы в пользу применения циклоспорина. Клиническая нефрология 2010; 3: 56-61Козловская ЛВ. Хронический гломерулонефрит: аргументы в пользу применения циклоспорина. Клиническая нефрология 2010; 3: 56-61Захарова ЕВ, Бирюкова ЛС. Роль циклоспорина в лечении идиопатического гломерулонефрита и волчаночного нефрита. Нефрология и диализ 2010; 12(2): 126-141Захарова ЕВ, Бирюкова ЛС. Роль циклоспорина в лечении идиопатического гломерулонефрита и волчаночного нефрита. Нефрология и диализ 2010; 12(2): 126-141Calne RY, Rolles K, White DJ et al. Cyclosporin A initiallyas the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers. Lancet 1979; 2 (8151):1033-1036Calne RY, Rolles K, White DJ et al. Cyclosporin A initiallyas the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers. Lancet 1979; 2 (8151):1033-1036Gallay PA. Cyclophilin inhibitors. Clin Liver Dis 2009; 13(3): 403-417Gallay PA. Cyclophilin inhibitors. Clin Liver Dis 2009; 13(3): 403-417Liu J, Farmer JD Jr, Lane WS et al. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 1991; 66(4): 807-815Liu J, Farmer JD Jr, Lane WS et al. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 1991; 66(4): 807-815Thomson AW. The spectrum of action of new immunosuppressive drugs. Clin Exp Immunol 1992; 89(2): 170-173Thomson AW. The spectrum of action of new immunosuppressive drugs. Clin Exp Immunol 1992; 89(2): 170-173Bram RJ, Hung DT, Martin PK et al. Identification of the immunophilins capable of mediating inhibition of signal transduction by cyclosporin A and FK506: roles of calcineurin binding and cellular location. Mol Cell Biol 1993; 13(8): 4760-4769Bram RJ, Hung DT, Martin PK et al. Identification of the immunophilins capable of mediating inhibition of signal transduction by cyclosporin A and FK506: roles of calcineurin binding and cellular location. Mol Cell Biol 1993; 13(8): 4760-4769Fruman DA, Burakoff SJ, Bierer BE. Immunophilins in protein folding and immunosuppression. FASEB J. 1994; 8(6): 391-400Fruman DA, Burakoff SJ, Bierer BE. Immunophilins in protein folding and immunosuppression. FASEB J. 1994; 8(6): 391-400Clardy J. The chemistry of signal transduction. Proc Natl Acad Sci USA 1995; 92(1): 56-61Clardy J. The chemistry of signal transduction. Proc Natl Acad Sci USA 1995; 92(1): 56-61Braun W, Kallen J, Mikol V et al. Three-dimensional structure and actions of immunosuppressants and their immunophilins. FASEB J. 1995: 9(1): 63-72Braun W, Kallen J, Mikol V et al. Three-dimensional structure and actions of immunosuppressants and their immunophilins. FASEB J. 1995: 9(1): 63-72Tajima K, Amakawa R, Ito T et al. Immunomodulatory effects of cyclosporin A on human peripheral blood dendritic cell subsets. Immunology 2003; 108(3):321-328Tajima K, Amakawa R, Ito T et al. Immunomodulatory effects of cyclosporin A on human peripheral blood dendritic cell subsets. Immunology 2003; 108(3):321-328Galat A, Bua J. Molecular aspects of cyclophilins mediating therapeutic actions of their ligands. Cell Mol Life Sci 2010; 67(20): 3467-3488Galat A, Bua J. Molecular aspects of cyclophilins mediating therapeutic actions of their ligands. Cell Mol Life Sci 2010; 67(20): 3467-3488Мейл Д. Иммунология /Д. Мейл, Дж. Бростофф, Д. Б. Рот, А. Ройтт/ Пер. с англ. М: Логосфера 2007. – 568 сМейл Д. Иммунология /Д. Мейл, Дж. Бростофф, Д. Б. Рот, А. Ройтт/ Пер. с англ. М: Логосфера 2007. – 568 сShalhoub RJ. Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet 1974; 2(7880): 556-560Shalhoub RJ. Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet 1974; 2(7880): 556-560Meyrier AY. Treatment of focal segmental glomerulosclerosis with immunophilin modulation: when did we stop thinking about pathogenesis? Kidney Int 2009; 76(5): 487-491Meyrier AY. Treatment of focal segmental glomerulosclerosis with immunophilin modulation: when did we stop thinking about pathogenesis? Kidney Int 2009; 76(5): 487-491Savin VJ, Sharma R, Lovell HB, Welling DJ. Measurement of albumin reflection coefficient with isolated rat glomeruli. J Am Soc Nephrol 1992; 3 (6): 1260-1269Savin VJ, Sharma R, Lovell HB, Welling DJ. Measurement of albumin reflection coefficient with isolated rat glomeruli. J Am Soc Nephrol 1992; 3 (6): 1260-1269Savin VJ, Sharma R, Sharma M et al. Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med 1996; 334 (14): 878-883Savin VJ, Sharma R, Sharma M et al. Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med 1996; 334 (14): 878-883Cattran D, Neogi T, Sharma R et al. Serial estimates of serum permeability activity and clinical correlates in patients with native kidney focal segmental glomerulosclerosis. J Am Soc Nephrol 2003; 14 (2): 448-453Cattran D, Neogi T, Sharma R et al. Serial estimates of serum permeability activity and clinical correlates in patients with native kidney focal segmental glomerulosclerosis. J Am Soc Nephrol 2003; 14 (2): 448-453Carraro M, Caridi G, Bruschi M et al. Serum glomerular permeability activity in patients with podocin mutations (NPHS2) and steroid-resistant nephrotic syndrome. J Am Soc Nephrol 2002; 13 (7): 1946-1952Carraro M, Caridi G, Bruschi M et al. Serum glomerular permeability activity in patients with podocin mutations (NPHS2) and steroid-resistant nephrotic syndrome. J Am Soc Nephrol 2002; 13 (7): 1946-1952Мухин НА, Тареева ИЕ, Краснова ТН, Шилов ЕМ, Мирошниченко НГ. Лечение нефротической формы хронического гломерулонефрита сандиммуном (циклоспорином А). Тер арх 1995; 67 (8): 13-15Мухин НА, Тареева ИЕ, Краснова ТН, Шилов ЕМ, Мирошниченко НГ. Лечение нефротической формы хронического гломерулонефрита сандиммуном (циклоспорином А). Тер арх 1995; 67 (8): 13-15Cattran DC, Appel GB, Hebert LA et al. A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. North America Nephrotic Syndrome Study Group. Kidney Int 1999; 56 (6): 2220-2226Cattran DC, Appel GB, Hebert LA et al. A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. North America Nephrotic Syndrome Study Group. Kidney Int 1999; 56 (6): 2220-2226Cattran DC, Appel GB, Hebert LA et al. Cyclosporine in patients with steroid-resistant membranous nephropathy: a randomized trial. Kidney Int 2001; 59 (4):1484-1490Cattran DC, Appel GB, Hebert LA et al. Cyclosporine in patients with steroid-resistant membranous nephropathy: a randomized trial. Kidney Int 2001; 59 (4):1484-1490Braun N, Schmutzler F, Lange C et al. Immunosuppressive treatment for focal segmental glomerulosclerosis in adults. Cochrane Database Syst Rev 2008; 16 (3): CD003233Braun N, Schmutzler F, Lange C et al. Immunosuppressive treatment for focal segmental glomerulosclerosis in adults. Cochrane Database Syst Rev 2008; 16 (3): CD003233Austin HA 3 rd , Illei GG, Braun MJ. Balow JE. Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy. J Am Soc Nephrol 2009; 20 (4): 901-911Austin HA 3 rd , Illei GG, Braun MJ. Balow JE. Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy. J Am Soc Nephrol 2009; 20 (4): 901-911Goumenos DS, Katopodis KP, Passadakis P et al. Corticosteroids and ciclosporin A in idiopathic membranous nephropathy: higher remission rates of nephrotic syndrome and less adverse reactions than after traditional treatment with cytotoxic drugs. Am J Nephrol 2007; 27 (3): 226-231Goumenos DS, Katopodis KP, Passadakis P et al. Corticosteroids and ciclosporin A in idiopathic membranous nephropathy: higher remission rates of nephrotic syndrome and less adverse reactions than after traditional treatment with cytotoxic drugs. Am J Nephrol 2007; 27 (3): 226-231Ronkainen J, Autio-Harmainen H, Nuutinen M. Cyclosporin A for the treatment of severe Henoch-Schцnlein glomerulonephritis. Pediatr Nephrol 2003; 18 (11): 1138-1142Ronkainen J, Autio-Harmainen H, Nuutinen M. Cyclosporin A for the treatment of severe Henoch-Schцnlein glomerulonephritis. Pediatr Nephrol 2003; 18 (11): 1138-1142Alexopoulos E, Papagianni A, Tsamelashvili M et al. Induction and long-term treatment with cyclosporine in membranous nephropathy with the nephrotic syndrome. Nephrol Dial Transplant 2006; 21 (11): 3127-3132Alexopoulos E, Papagianni A, Tsamelashvili M et al. Induction and long-term treatment with cyclosporine in membranous nephropathy with the nephrotic syndrome. Nephrol Dial Transplant 2006; 21 (11): 3127-3132Ogawa H, Kameda H, Amano K, Takeuchi T. Efficacy and safety of cyclosporine A in patients with refractory systemic lupus erythematosus in a daily clinical practice. Lupus 2010; 19 (2): 162-169Ogawa H, Kameda H, Amano K, Takeuchi T. Efficacy and safety of cyclosporine A in patients with refractory systemic lupus erythematosus in a daily clinical practice. Lupus 2010; 19 (2): 162-169Kiyomasu T, Shibata M, Kurosu H et al. Cyclosporin A treatment for membranoproliferative glomerulonephritis type II. Nephron 2002; 91 (3):509-511Kiyomasu T, Shibata M, Kurosu H et al. Cyclosporin A treatment for membranoproliferative glomerulonephritis type II. Nephron 2002; 91 (3):509-511Shin JI, Park JM, Shin YH et al. Cyclosporin A therapy for severe Henoch-Schцnlein nephritis with nephrotic syndrome. Pediatr Nephrol 2005; 20 (8):1093-1097Shin JI, Park JM, Shin YH et al. Cyclosporin A therapy for severe Henoch-Schцnlein nephritis with nephrotic syndrome. Pediatr Nephrol 2005; 20 (8):1093-1097Plank C, Kalb V, Hinkes B et al. Cyclosporin A is sperior to cyclophosphamide in children with steroid-resistant nephrotic syndrome-a randomized controlled multicentre trial by the Arbeitsgemeinschaft fьr Pдdiatrische Nephrologie. Pediatr Nephrol 2008; 23 (9): 1483-1493Plank C, Kalb V, Hinkes B et al. Cyclosporin A is sperior to cyclophosphamide in children with steroid-resistant nephrotic syndrome-a randomized controlled multicentre trial by the Arbeitsgemeinschaft fьr Pдdiatrische Nephrologie. Pediatr Nephrol 2008; 23 (9): 1483-1493Heidet L, Bongers EM, Sich M et al. In vivo expression of putative LMX1B targets in nail-patella syndrome kidneys. Am J Pathol 2003; 163 (1): 145-155Heidet L, Bongers EM, Sich M et al. In vivo expression of putative LMX1B targets in nail-patella syndrome kidneys. Am J Pathol 2003; 163 (1): 145-155Meyrier A. Antiproteinuric and immunological effects of cyclosporin A in the treatment of glomerular diseases. Nephrol Dial Transplant 1992; 7 Suppl 1: 80-84Meyrier A. Antiproteinuric and immunological effects of cyclosporin A in the treatment of glomerular diseases. Nephrol Dial Transplant 1992; 7 Suppl 1: 80-84Schrijver G, Assmann KJ, Wetzels JF, Berden JH. Cyclosporin A reduces albuminuria in experimental anti-GBM nephritis independently from changes in GFR. Nephrol Dial Transplant 1995; 10 (7): 1149-1154Schrijver G, Assmann KJ, Wetzels JF, Berden JH. Cyclosporin A reduces albuminuria in experimental anti-GBM nephritis independently from changes in GFR. Nephrol Dial Transplant 1995; 10 (7): 1149-1154Zietse R, Wenting GJ, Kramer P et al. Effects of cyclosporin A on glomerular barrier function in the nephrotic syndrome. Clin Sci (Lond) 1992; 82 (6): 641-650Zietse R, Wenting GJ, Kramer P et al. Effects of cyclosporin A on glomerular barrier function in the nephrotic syndrome. Clin Sci (Lond) 1992; 82 (6): 641-650Kanwar YS, Linker A, Farquhar MG. Increased permeability of the glomerular basement membrane to ferritin after removal of glycosaminoglycans (heparan sulfate) by enzyme digestion. J Cell Biol 1980; 86 (2): 688-693Kanwar YS, Linker A, Farquhar MG. Increased permeability of the glomerular basement membrane to ferritin after removal of glycosaminoglycans (heparan sulfate) by enzyme digestion. J Cell Biol 1980; 86 (2): 688-693Rossi M, Morita H, Sormunen R et al. Heparan sulfate chains of perlecan are indispensable in the lens capsule but not in the kidney. EMBO J 2003; 22 (2): 236-245Rossi M, Morita H, Sormunen R et al. Heparan sulfate chains of perlecan are indispensable in the lens capsule but not in the kidney. EMBO J 2003; 22 (2): 236-245Harvey SJ, Jarad G, Cunningham J et al. Disruption of glomerular basement membrane charge through podocyte-specific mutation of agrin does not alter glomerular permselectivity. Am J Pathol 2007; 171 (1): 139-152Harvey SJ, Jarad G, Cunningham J et al. Disruption of glomerular basement membrane charge through podocyte-specific mutation of agrin does not alter glomerular permselectivity. Am J Pathol 2007; 171 (1): 139-152Bensman A, Niaudet P. Non-immunologic mechanisms of calcineurin inhibitors explain its antiproteinuric effects in genetic glomerulopathies. Pediatr Nephrol 2010; 25 (7): 1197-1199Bensman A, Niaudet P. Non-immunologic mechanisms of calcineurin inhibitors explain its antiproteinuric effects in genetic glomerulopathies. Pediatr Nephrol 2010; 25 (7): 1197-1199Charbit M, Gubler MC, Dechaux M et al. Cyclosporin therapy in patients with Alport syndrome. Pediatr Nephrol 2007; 22 (1): 57-63Charbit M, Gubler MC, Dechaux M et al. Cyclosporin therapy in patients with Alport syndrome. Pediatr Nephrol 2007; 22 (1): 57-63Massella L, Muda AO, Legato A et al. Cyclosporine A treatment in patients with Alport syndrome: a single-center experience. Pediatr Nephrol 2010; 25 (7): 1269-1275Massella L, Muda AO, Legato A et al. Cyclosporine A treatment in patients with Alport syndrome: a single-center experience. Pediatr Nephrol 2010; 25 (7): 1269-1275Malina M, Cinek O, Janda J, Seeman T. Partial remission with cyclosporine A in a patient with nephrotic syndrome due to NPHS2 mutation. Pediatr Nephrol 2009; 24 (10): 2051-2053Malina M, Cinek O, Janda J, Seeman T. Partial remission with cyclosporine A in a patient with nephrotic syndrome due to NPHS2 mutation. Pediatr Nephrol 2009; 24 (10): 2051-2053Ruf RG, Lichtenberger A, Karle SM et al. Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol 2004; 15 (3): 722-732Ruf RG, Lichtenberger A, Karle SM et al. Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol 2004; 15 (3): 722-732Gellermann J, Stefanidis CJ, Mitsioni A, Querfeld U. Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations. Pediatr Nephrol 2010; 25 (7): 1285-1289Gellermann J, Stefanidis CJ, Mitsioni A, Querfeld U. Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations. Pediatr Nephrol 2010; 25 (7): 1285-1289Faul C, Asanuma K, Yanagida-Asanuma E et al. Actin up: regulation of podocyte structure and function by components of the actin cytoskeleton. Trends Cell Biol 2007; 17 (9): 428-437Faul C, Asanuma K, Yanagida-Asanuma E et al. Actin up: regulation of podocyte structure and function by components of the actin cytoskeleton. Trends Cell Biol 2007; 17 (9): 428-437Mundel P, Reiser J. Proteinuria: an enzymatic disease of the podocyte? Kidney Int 2010; 77 (7): 571-580Mundel P, Reiser J. Proteinuria: an enzymatic disease of the podocyte? Kidney Int 2010; 77 (7): 571-580Kriz W, Hackenthal E, Nobiling R et al. A role for podocytes to counteract capillary wall distension. Kidney Int 1994; 45 (2): 369-376Kriz W, Hackenthal E, Nobiling R et al. A role for podocytes to counteract capillary wall distension. Kidney Int 1994; 45 (2): 369-376St John PL, Abrahamson DR. Glomerular endothelial cells and podocytes jointly synthesize laminin-1 and -11 chains. Kidney Int 2001; 60 (3): 1037-1046St John PL, Abrahamson DR. Glomerular endothelial cells and podocytes jointly synthesize laminin-1 and -11 chains. Kidney Int 2001; 60 (3): 1037-1046Ina K, Kitamura H, Tatsukawa S et al. Clomerular podocyte endocytosis of the diabetic rat. J Electron Microsc (Tokyo) 2002; 51 (4): 275-279Ina K, Kitamura H, Tatsukawa S et al. Clomerular podocyte endocytosis of the diabetic rat. J Electron Microsc (Tokyo) 2002; 51 (4): 275-279Tryggvason K, Wartiovaara J. Molecular basis of glomerular permselectivity. Curr Opin Nephrol Hypertens 2001; 10 (4): 543-549Tryggvason K, Wartiovaara J. Molecular basis of glomerular permselectivity. Curr Opin Nephrol Hypertens 2001; 10 (4): 543-549Kestila M, Lenkkeri U, Mдnnikkц M et al. Positionally cloned gene for a novel glomerular protein-nephrinis mutated in congenital nephrotic syndrome. Mol Cell 1998; 1 (4): 575-582Kestila M, Lenkkeri U, Mдnnikkц M et al. Positionally cloned gene for a novel glomerular protein-nephrinis mutated in congenital nephrotic syndrome. Mol Cell 1998; 1 (4): 575-582Faul C, Donnelly M, Merscher-Gomez S et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 2008; 14 (9): 931-938Faul C, Donnelly M, Merscher-Gomez S et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 2008; 14 (9): 931-938Miao J, Fan Q, Cui Q et al. Newly identified cytoskeletal components are associated with dynamic changes of podocyte foot processes. Nephrol Dial Transplant 2009; 24 (11): 3297-3305Miao J, Fan Q, Cui Q et al. Newly identified cytoskeletal components are associated with dynamic changes of podocyte foot processes. Nephrol Dial Transplant 2009; 24 (11): 3297-3305Yoshikawa N, Ito H, Akamatsu R et al. Clomerular podocyte vacuolation in focal segmental glomerulosclerosis. Arch Pathol Lab Med 1986; 110 (5): 394-398Yoshikawa N, Ito H, Akamatsu R et al. Clomerular podocyte vacuolation in focal segmental glomerulosclerosis. Arch Pathol Lab Med 1986; 110 (5): 394-398Farquhar MG, Palade GE. Clomerular permeability. II. Ferritin transfer across the glomerular capillary wall in nephrotic rats. J Exp Med 1961; 114: 699-716Farquhar MG, Palade GE. Clomerular permeability. II. Ferritin transfer across the glomerular capillary wall in nephrotic rats. J Exp Med 1961; 114: 699-716Craham RC Jr, Karnovsky MJ. Clomerular permeability. Ultrastructural cytochemical studies using peroxidases as protein tracers. J Exp Med 1966; 124 (6): 1123-1134Craham RC Jr, Karnovsky MJ. Clomerular permeability. Ultrastructural cytochemical studies using peroxidases as protein tracers. J Exp Med 1966; 124 (6): 1123-1134Van den Berg JG, van den Bergh Weerman MA, Assmann KJ et al. Podocyte foot process effacement is not correlated with the level of proteinuria in human glomerulopathies. Kidney Int 2004; 66 (5): 1901-1906Van den Berg JG, van den Bergh Weerman MA, Assmann KJ et al. Podocyte foot process effacement is not correlated with the level of proteinuria in human glomerulopathies. Kidney Int 2004; 66 (5): 1901-1906Chuang PY, He JC. Signaling in regulation of podocyte phenotypes. Nephron Physiol 2009; 111 (2): p9-15Chuang PY, He JC. Signaling in regulation of podocyte phenotypes. Nephron Physiol 2009; 111 (2): p9-15Ina K, Kitamura H, Tatsukawa S et al. Clomerular podocyte endocytosis of the diabetic rat. J Electron Microsc (Tokyo) 2002; 51 (4): 275-279Ina K, Kitamura H, Tatsukawa S et al. Clomerular podocyte endocytosis of the diabetic rat. J Electron Microsc (Tokyo) 2002; 51 (4): 275-279Hartleben B, Godel M, Meyer-Schwesinger C. et al. Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. J Clin Invest 2010; 120 (4): 1084-1096Hartleben B, Godel M, Meyer-Schwesinger C. et al. Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. J Clin Invest 2010; 120 (4): 1084-1096Morigi M, Buelli S, Angioletti S et al. In response to protein load podocytes reorganize cytoskeleton and modulate endothelin-1 gene: implication for permselective dysfunction of chronic nephropathies. Am J Pathol 2005; 166 (5): 1309-1320Morigi M, Buelli S, Angioletti S et al. In response to protein load podocytes reorganize cytoskeleton and modulate endothelin-1 gene: implication for permselective dysfunction of chronic nephropathies. Am J Pathol 2005; 166 (5): 1309-1320Смирнов АВ, Добронравов ВА, Неворотин АИ и др. Гомоцистеин вызывает повреждения не только клубочкового, но и канальцевого отдела нефрона. Нефрология 2005; 9 (3): 81-87Смирнов АВ, Добронравов ВА, Неворотин АИ и др. Гомоцистеин вызывает повреждения не только клубочкового, но и канальцевого отдела нефрона. Нефрология 2005; 9 (3): 81-87Смирнов АВ, Добронравов ВА, Неворотин АИ и др. Гипергомоцистеинемия усугубляет повреждения нефрона при экспериментальной хронической почечной недостаточности. Нефрология 2005; 9 (4): 67-74Смирнов АВ, Добронравов ВА, Неворотин АИ и др. Гипергомоцистеинемия усугубляет повреждения нефрона при экспериментальной хронической почечной недостаточности. Нефрология 2005; 9 (4): 67-74Tipping PG. Are podocytes passive or provocative in proteinuric glomerular pathology? J Am Soc Nephrol 2008; 19 (4): 651-653Tipping PG. Are podocytes passive or provocative in proteinuric glomerular pathology? J Am Soc Nephrol 2008; 19 (4): 651-653Abe K, Miyazaki M, Koji T et al. Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization. Kidney Int 2001; 60 (1): 137-146Abe K, Miyazaki M, Koji T et al. Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization. Kidney Int 2001; 60 (1): 137-146Nangaku M, Shankland SJ, Couser WG. Cellular response to injury in membranous nephropathy. J Am Soc Nephrol 2005; 16 (5): 1195-1204Nangaku M, Shankland SJ, Couser WG. Cellular response to injury in membranous nephropathy. J Am Soc Nephrol 2005; 16 (5): 1195-1204Couser WG, Nangaku M. Cellular and molecular biology of membranous nephropathy. J Nephrol 2006; 19 (6): 699-705Couser WG, Nangaku M. Cellular and molecular biology of membranous nephropathy. J Nephrol 2006; 19 (6): 699-705Topham PS, Haydar SA, Kuphal R et al. Complement-mediated injury reversibly disrupts glomerular epithelial cell actin microfilaments and focal adhesions. Kidney Int 1999; 55 (5): 1763-1775Topham PS, Haydar SA, Kuphal R et al. Complement-mediated injury reversibly disrupts glomerular epithelial cell actin microfilaments and focal adhesions. Kidney Int 1999; 55 (5): 1763-1775Yuan H, Takeuchi E, Taylor GA et al. Nephrin dissociates from actin, and its expression is reduced in early experimental membranous nephropathy. J Am Soc Nephrol 2002; 13 (4): 946-956Yuan H, Takeuchi E, Taylor GA et al. Nephrin dissociates from actin, and its expression is reduced in early experimental membranous nephropathy. J Am Soc Nephrol 2002; 13 (4): 946-956Saran AM, Yuan H, Takeuchi E et al. Complement mediates nephrin redistribution and actin dissociation in experimental membranous nephropathy. Kidney Int 2003; 64 (6): 2072-2078Saran AM, Yuan H, Takeuchi E et al. Complement mediates nephrin redistribution and actin dissociation in experimental membranous nephropathy. Kidney Int 2003; 64 (6): 2072-2078Doublier S, Ruotsalainen V, Salvidio G et al. Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome. Am J Pathol 2001; 158 (5): 1723-1731Doublier S, Ruotsalainen V, Salvidio G et al. Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome. Am J Pathol 2001; 158 (5): 1723-1731Beck LH Jr, Bonegio RG, Lambeau G et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009; 361 (1): 11-21Beck LH Jr, Bonegio RG, Lambeau G et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009; 361 (1): 11-21Glassock RJ Human idiopathic membranous nephropathy-a mystery solved? N Engl J Med 2009; 361 (1): 81-83Glassock RJ Human idiopathic membranous nephropathy-a mystery solved? N Engl J Med 2009; 361 (1): 81-83Ronco P, Debiec H. Antigen identification in membranous nephropathy moves toward targeted monitoring and new therapy. J Am Soc Nephrol 2010; 21 (4): 564-569Ronco P, Debiec H. Antigen identification in membranous nephropathy moves toward targeted monitoring and new therapy. J Am Soc Nephrol 2010; 21 (4): 564-569Lai KN, Leung JC, Chan LY et al. Podocyte injury induced by mesangial-derived cytokines in IgA nephropathy. Nephrol Dial Transplant 2009; 24 (1): 62-72Lai KN, Leung JC, Chan LY et al. Podocyte injury induced by mesangial-derived cytokines in IgA nephropathy. Nephrol Dial Transplant 2009; 24 (1): 62-72Li Y, Kang YS, Dai C et al. Epithelial–to-mesenchymal transition is a potential pathway leading to podocyte dysfunction and proteinuria. Am J Pathol 2008; 172 (2): 299-308Li Y, Kang YS, Dai C et al. Epithelial–to-mesenchymal transition is a potential pathway leading to podocyte dysfunction and proteinuria. Am J Pathol 2008; 172 (2): 299-308Reiser J, von Gersdorff G, Loos M et al. Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest 2004; 113 (10): 1390-1397Reiser J, von Gersdorff G, Loos M et al. Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest 2004; 113 (10): 1390-1397Banas MC, Banas B, Hudkins KL et al. TLR4 links podocytes with the innate immune system to mediate glomerular injury. J Am Soc Nephrol 2008; 19 (4): 704-713Banas MC, Banas B, Hudkins KL et al. TLR4 links podocytes with the innate immune system to mediate glomerular injury. J Am Soc Nephrol 2008; 19 (4): 704-713D’Agati VD. Podocyte injury in focal segmental glomerulosclerosis: Lessons from animal models (a play in five acts). Kidney Int 2008; 73 (4): 399-406D’Agati VD. Podocyte injury in focal segmental glomerulosclerosis: Lessons from animal models (a play in five acts). Kidney Int 2008; 73 (4): 399-406Shankland SJ. The podocyte’s response to injury: role in proteinuria and glomerulosclerosis. Kidney Int 2006; 69(12): 2131-2147Shankland SJ. The podocyte’s response to injury: role in proteinuria and glomerulosclerosis. Kidney Int 2006; 69(12): 2131-2147Torbjornsdotter TB, Perrin NE, Jaremko GA, Berg UB. Widening of foot processes in normoalbuminuric adolescents with type 1 diabetes. Pediatr Nephrol 2005; 20 (6): 750-758Torbjornsdotter TB, Perrin NE, Jaremko GA, Berg UB. Widening of foot processes in normoalbuminuric adolescents with type 1 diabetes. Pediatr Nephrol 2005; 20 (6): 750-758White KE, Bilous RW, Marshall SM et al. Podocyte number in normotensive type 1 diabetic patients with albuminuria. Diabetes 2002; 51 (10): 3083-3089White KE, Bilous RW, Marshall SM et al. Podocyte number in normotensive type 1 diabetic patients with albuminuria. Diabetes 2002; 51 (10): 3083-3089Meyer TW, Bennett PH, Nelson RG. Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria. Diabetologia 1999; 42 (11): 1341-1344Meyer TW, Bennett PH, Nelson RG. Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria. Diabetologia 1999; 42 (11): 1341-1344Fioretto P, Mauer M. Histopathology of diabetic nephropathy. Semin Nephrol 2007; 27 (2): 195-207Fioretto P, Mauer M. Histopathology of diabetic nephropathy. Semin Nephrol 2007; 27 (2): 195-207Wiggins RC The spectrum of podocytopathies: a unifying view of glomerular diseases. Kidney Int 2007; 71 (12): 1205-1214Wiggins RC The spectrum of podocytopathies: a unifying view of glomerular diseases. Kidney Int 2007; 71 (12): 1205-1214Patrakka J, Truggvason K. New insights into the role of podocytes in proteinuria. Nat Rev Nephrol 2009; 5 (8): 463-468Patrakka J, Truggvason K. New insights into the role of podocytes in proteinuria. Nat Rev Nephrol 2009; 5 (8): 463-468Reiser J, Gupta V, Kistler AD. Toward the development of podocyte-specific drugs. Kidney Int 2010; 77 (8): 662-668Reiser J, Gupta V, Kistler AD. Toward the development of podocyte-specific drugs. Kidney Int 2010; 77 (8): 662-668Kriz W. Podocyte is the major culprit accounting for the progression of chronic renal disease. Microsc Res Tech 2002; 57 (4): 189-195Kriz W. Podocyte is the major culprit accounting for the progression of chronic renal disease. Microsc Res Tech 2002; 57 (4): 189-195Kim YH, Goyal M, Kurnit D et al. Podocyte depletion and glomerulosclerosis have a direct relationship in the PAN-treated rat. Kidney Int 2001; 60 (3): 957-968Kim YH, Goyal M, Kurnit D et al. Podocyte depletion and glomerulosclerosis have a direct relationship in the PAN-treated rat. Kidney Int 2001; 60 (3): 957-968Wharram BL, Goyal M, Wiggins JE et al. Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J Am Soc Nephrol 2005; 16 (10): 2941-2952Wharram BL, Goyal M, Wiggins JE et al. Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J Am Soc Nephrol 2005; 16 (10): 2941-2952Kretzler M. Role of podocytes in focal sclerosis: defining the point of no return. J Am Soc Nephrol 2005; 16 (10): 2830-2832Kretzler M. Role of podocytes in focal sclerosis: defining the point of no return. J Am Soc Nephrol 2005; 16 (10): 2830-2832Fogo AB Glomerular hypertension, abnormal glomerular growth, and progression of renal diseases. Kidney Int Suppl 2000; 75: S15-21Fogo AB Glomerular hypertension, abnormal glomerular growth, and progression of renal diseases. Kidney Int Suppl 2000; 75: S15-21Lu TC, He JC, Klotman PE. Podocytes in HIV-associated nephropathy. Nephron Clin Pract 2007; 106 (2): c67-71Lu TC, He JC, Klotman PE. Podocytes in HIV-associated nephropathy. Nephron Clin Pract 2007; 106 (2): c67-71He JC, Husain M, Sunamoto M et al. Nef stimulates proliferation of glomerular podocytes through activation of Src-dependent Stat3 and MAPK1, 2 pathways. J Clin Invest 2004; 114 (5): 643-651He JC, Husain M, Sunamoto M et al. Nef stimulates proliferation of glomerular podocytes through activation of Src-dependent Stat3 and MAPK1, 2 pathways. J Clin Invest 2004; 114 (5): 643-651Korgaonkar SN, Feng X, Ross MD et al. HIV-1 upregulates VEGF in podocytes. J Am Soc Nephrol 2008; 19 (5): 877-883Korgaonkar SN, Feng X, Ross MD et al. HIV-1 upregulates VEGF in podocytes. J Am Soc Nephrol 2008; 19 (5): 877-883Barisoni L, Schnaper HW, Kopp JB. A proposed taxonomy for the podocytopathies: a reassessment of the primary nephrotic diseases. Clin J Am Soc Nephrol 2007; 2 (3): 529-542Barisoni L, Schnaper HW, Kopp JB. A proposed taxonomy for the podocytopathies: a reassessment of the primary nephrotic diseases. Clin J Am Soc Nephrol 2007; 2 (3): 529-542Mathieson PW. Proteinuria and immunity – an overstated relationship? N Engl J Med 2008; 359 (23): 2492-2494Mathieson PW. Proteinuria and immunity – an overstated relationship? N Engl J Med 2008; 359 (23): 2492-2494Mathieson PW. Podocyte actin in health, disease and treatment. Nephrol Dial Transplant 2010; 25 (6): 1772-1773Mathieson PW. Podocyte actin in health, disease and treatment. Nephrol Dial Transplant 2010; 25 (6): 1772-1773Yanagida-Asanuma E, Asanuma K, Kim K et al. Synaptopodin protects against proteinuria by disrupting Cdc42: IRSp53: Mena signaling complexes in kidney podocytes. Am J Pathol2007; 171 (2): 415-427Yanagida-Asanuma E, Asanuma K, Kim K et al. Synaptopodin protects against proteinuria by disrupting Cdc42: IRSp53: Mena signaling complexes in kidney podocytes. Am J Pathol2007; 171 (2): 415-427Asanuma K, Kim K, Oh J et al. Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner. J Clin Invest 2005; 115 (5): 1188-1198Asanuma K, Kim K, Oh J et al. Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner. J Clin Invest 2005; 115 (5): 1188-1198Asanuma K, Yanagida-Asanuma E, Faul C et al. Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signalling. Nat Cell Biol 2006; 8 (5): 485-491Asanuma K, Yanagida-Asanuma E, Faul C et al. Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signalling. Nat Cell Biol 2006; 8 (5): 485-491Yan K, Kudo A, Hirano H et al. Subcellular localization of glucocorticoid receptor protein in the human kidney glomerulus. Kidney Int 1999; 56 (1): 65-73Yan K, Kudo A, Hirano H et al. Subcellular localization of glucocorticoid receptor protein in the human kidney glomerulus. Kidney Int 1999; 56 (1): 65-73Xing CY, Saleem MA, Coward RJ et al. Direct effects of dexamethasone on human podocytes. Kidney Int 2006; 70 (6): 1038-1045Xing CY, Saleem MA, Coward RJ et al. Direct effects of dexamethasone on human podocytes. Kidney Int 2006; 70 (6): 1038-1045Castellino F, Heuser J, Marchetti S et al. Glucocorticoid stabilization of actin filaments: a possible mechanism for inhibition of corticotropin release. Proc Natl Acad Sci USA 1992; 89 (9): 3775-3779Castellino F, Heuser J, Marchetti S et al. Glucocorticoid stabilization of actin filaments: a possible mechanism for inhibition of corticotropin release. Proc Natl Acad Sci USA 1992; 89 (9): 3775-3779Koukouritaki SB, Lianos EA. Glucocorticoid effect on human mesangial cell cytoskeletal proteins. J Lab Clin Med 1999; 133 (4): 378-383Koukouritaki SB, Lianos EA. Glucocorticoid effect on human mesangial cell cytoskeletal proteins. J Lab Clin Med 1999; 133 (4): 378-383Ranson RF, Lam NG, Hallett MA et al. Glucocorticoids protect and enhance recovery of cultured murine podocytes via actin filament stabilization. Kidney Int 2005; 68 (6): 2473-2483Ranson RF, Lam NG, Hallett MA et al. Glucocorticoids protect and enhance recovery of cultured murine podocytes via actin filament stabilization. Kidney Int 2005; 68 (6): 2473-2483Wada T, Pippin JW, Marshall CB et al. Dexamethasone prevents podocyte apoptosis induced by puromycin aminonucleoside: role of p53 and Bcl-2-related family proteins. J Am Soc Nephrol 2005; 16 (9): 2615-2625Wada T, Pippin JW, Marshall CB et al. Dexamethasone prevents podocyte apoptosis induced by puromycin aminonucleoside: role of p53 and Bcl-2-related family proteins. J Am Soc Nephrol 2005; 16 (9): 2615-2625Wada T, Pippin JW, Nangaku M, Shankland SJ. Dexamethasone’s prosurvival benefits in podocytes reguire extracellular signal-regulated kinase phosphorylation. Nephron Exp Nephrol 2008; 109 (1): e8-19Wada T, Pippin JW, Nangaku M, Shankland SJ. Dexamethasone’s prosurvival benefits in podocytes reguire extracellular signal-regulated kinase phosphorylation. Nephron Exp Nephrol 2008; 109 (1): e8-19Wagrowska-Danilewicz M, Danilewicz M. Synaptopodin immunoexpression in steroid-responsive and steroid-resistant minimal change disease and focal segmental glomerulosclerosis. Nefrologia 2007; 27 (6): 710-715Wagrowska-Danilewicz M, Danilewicz M. Synaptopodin immunoexpression in steroid-responsive and steroid-resistant minimal change disease and focal segmental glomerulosclerosis. Nefrologia 2007; 27 (6): 710-715Ehrich JH, Geerlings C, Zivicnjak M et al. Steroid-resistant idiopathic childhood nephrosis: overdiagnosed and undertreated. Nephrol Dial Transplant 2007; 22 (8): 2183-2193Ehrich JH, Geerlings C, Zivicnjak M et al. Steroid-resistant idiopathic childhood nephrosis: overdiagnosed and undertreated. Nephrol Dial Transplant 2007; 22 (8): 2183-2193Jain KK. Challenges of drug discovery for personalized medicine. Curr Opin Mol Ther 2006; 8 (6): 487-492Jain KK. Challenges of drug discovery for personalized medicine. Curr Opin Mol Ther 2006; 8 (6): 487-492

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