transplantologiyaТрансплантологияTransplantologiya. The Russian Journal of Transplantation2074-05062542-0909IPO Association of Transplantologists10.23873/2074-0506-2009-0-1-19-31transplantologiya-235Research ArticleОБЗОРНЫЕ СТАТЬИ И ЛЕКЦИИREVIEW ARTICLES AND LECTURESПоздняя дисфункция трансплантированной почки: морфологическая структура, критерии диагностикиLate grafted kidney dysfunction: morphological structure, criteria for diagnosisСтоляревичЕ. С.StolyarevichE. S.

кафедра нефрологии

Екатерина Сергеевна Столяревич 

Department of Nephrology

stolyarevich@yandex.ruТомилинаН. А.TomilinaN. A.

кафедра нефрологии

Department of Nephrology,

ФГУ НИИ трансплантологии и искусственных органов, ФПДО МГМСУРоссияResearch Institute of Transplantology and Artificial Organs, Faculty of Postgraduate Education, Moscow State Medical University of DentistryRussian Federation200916082018011931Copyright © Столяревич Е.С., Томилина Н.А., 20182018Столяревич Е.С., Томилина Н.А.Stolyarevich E.S., Tomilina N.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.jtransplantologiya.ru/jour/article/view/235

Патология трансплантированной почки включает в себя широкий спектр заболеваний, различающихся по своей природе, механизмам развития и темпам прогрессирования. В ранние сроки после трансплантации почки важнейшей причиной дисфункции трансплантата остается острое отторжение, возникающее вследствие ответа иммунной системы реципиента на трансплантационные антигены донора и развивающееся с активацией как клеточного, так и гуморального звена иммунного ответа. На поздних сроках одной из основных причин отдаленных потерь трансплантированной почки является хроническая дисфункция трансплантата, морфологическим субстратом которой является прогрессирующий нефросклероз. Развитие нефросклероза в трансплантате, как правило, связано с сочетанным действием целого ряда как иммунных, так и неспецифических факторов, однако в большинстве случаев особенности морфологической картины позволяют выявить преобладание того или иного механизма в его происхождении и в соответствии с этим выделять отдельные нозологические формы. К последним относятся хроническое отторжение, нефротоксичность, индуцированная ингибиторами кальциневрина, а также нефросклероз, вызванный причинами, не связанными с отторжением, такими как ишемически-реперфузионное повреждение, обструктивная нефропатия, вирусное поражение трансплантата и др. Также по мере увеличения срока с момента аллотрансплантации почки (АТП)возрастает и частота возвратной и de novo патологии, наиболее распространенными вариантами которой являются IgA-нефропатия, фокальный сегментарный гломерулосклероз, мембранозная нефропатия, диабетическая нефропатия и др. Пункционная биопсия с использованием иммунофлюоресценции и электронной микроскопии и является «золотым стандартом» диагностики патологии трансплантированной почки, поскольку лишь морфологическая верификация диагноза позволяет подобрать адекватную иммуносупрессивную терапию и тем самым улучшить отдаленные результаты АТП. В статье приведены критерии диагностики и особенности морфологической картины различных вариантов патологии почечного трансплантата.

Grafted kidney abnormalities include a wide spectrum of diseases that differ in their nature, mechanisms of development, and rates of progression. In the early period after renal transplantation, the most important cause of graft dysfunction remains to be acute rejection that results from a recipient's immunological response to a donor's transplantation antigens and develops with the activation of both cellular and humural immune responses. In the late periods, one of the main causes of late graft losses is chronic graft dysfunction, the morphological substrate of which is progressive nephrosclerosis. The development of graft nephrosclerosis is generally associated with the combined effects of a large variety of both immune and nonspecific factors; however, the morphological features make it possible to identify the preponderance of this or that mechanism in its origin and, in this connection, individual nosological entities. The latter include chronic rejection, calcineurin inhibitorinduced nephrotoxicity, and nephrosclerosis caused by rejection-unassociated conditions, such as ischemic-reperfusion lesion, obstructive nephropathy, viral graft damage, etc. Moreover, as more time elapses after renal allotransplantation (RAT), there is a higher incidence of recurrent and de novo diseases, the most common types of which are IgA-nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, diabetic nephropathy, etc. Puncture biopsy using immunofluorescence and electron microscopy is the gold standard of the diagnosis of graft kidney abnormalities since only the morphological verification of the diagnosis permits adequate immunosuppressive therapy, by improving the long-term results of RAT. The paper presents diagnostic criteria and morphological features of different types of renal graft diseases.

патология почечного трансплантатаотторжениенефросклерознефротоксичность ингибиторв кальцинейринавозвратный гломерулонефритrenal graft diseasesrejectionnephrosclerosisnephrotoxicity of calcineurin inhibitorsrecurrent glomerulonephritisReferencesColvin R.B., Nickeliet V. Renal transplant pathology. Jennette J.C. et al. (eds). Heptinstall’s Pathology of the kidney. Philadelphia: Lippincott-Raven, 2006. p. 1348—490.Colvin R.B., Nickeliet V. Renal transplant pathology. Jennette J.C. et al. (eds). Heptinstall’s Pathology of the kidney. Philadelphia: Lippincott-Raven, 2006. p. 1348—490.Solez K., Axelsen R.A., Benediktsson H. et al. International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney Int 1993;44:411—22.Solez K., Axelsen R.A., Benediktsson H. et al. International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney Int 1993;44:411—22.Racusen L.C., Solez K., Colvin R.B. et al. The Banff 97 working classification of renal allograft pathology. Kidney Int 1999;55:713—23.Racusen L.C., Solez K., Colvin R.B. et al. The Banff 97 working classification of renal allograft pathology. Kidney Int 1999;55:713—23.Racusen L.C., Solez K., Mihatscg M.J. et al Antibody-mediated rejection criteria — an addition to the Banff 97 classification of renal allograft rejection. Am J Transplant 2003;3:708.Racusen L.C., Solez K., Mihatscg M.J. et al Antibody-mediated rejection criteria — an addition to the Banff 97 classification of renal allograft rejection. Am J Transplant 2003;3:708.Solez K., Colvin R. B., Racusen L. C. et al. Banff '05 Meeting Report: Differential Diagnosis of Chronic Allograft Injury and Elimination of Chronic Allograft Nephropathy ('CAN'). Am J Transplant 2007;21(3):518—26.Solez K., Colvin R. B., Racusen L. C. et al. Banff '05 Meeting Report: Differential Diagnosis of Chronic Allograft Injury and Elimination of Chronic Allograft Nephropathy ('CAN'). Am J Transplant 2007;21(3):518—26.Colvin R.B., Cohen A.H., Saiontz C. et al. Evaluation of pathologic criteria for acute renal allograft rejection: reproducibility, sensitivity, and clinical correlation. J Am Soc Nephrol 1997;8:1930—41.Colvin R.B., Cohen A.H., Saiontz C. et al. Evaluation of pathologic criteria for acute renal allograft rejection: reproducibility, sensitivity, and clinical correlation. J Am Soc Nephrol 1997;8:1930—41.Шумаков В.И., Левицкий Э.Р., Порядин Н.Ф. Синдром отторжения при трансплантации почки. М.: Медицина, 1982; с. 106—7.Шумаков В.И., Левицкий Э.Р., Порядин Н.Ф. Синдром отторжения при трансплантации почки. М.: Медицина, 1982; с. 106—7.Шумаков В.И., Мойсюк Я.Г., Томилина Н.А. и др. Трансплантация почки. В кн.: Трансплантология. Под ред. В.И. Шумакова. М.: Медицина, 1995; с. 194—6.Шумаков В.И., Мойсюк Я.Г., Томилина Н.А. и др. Трансплантация почки. В кн.: Трансплантология. Под ред. В.И. Шумакова. М.: Медицина, 1995; с. 194—6.Hamburger I. A reappraisal of the concept of organ «rejection», based on the study of homotransplanted kidneys. Transplantation 1967;5(4): 870—84.Hamburger I. A reappraisal of the concept of organ «rejection», based on the study of homotransplanted kidneys. Transplantation 1967;5(4): 870—84.Resch L., Yu W., Fraser R.B. et al. T-cell/periodic acid-Shiff stain: a useful tool in the evaluation of tubulointerstitial infiltrates as a component of renal allograft rejection. Ann Diagn Pathol 2002;6:122—4.Resch L., Yu W., Fraser R.B. et al. T-cell/periodic acid-Shiff stain: a useful tool in the evaluation of tubulointerstitial infiltrates as a component of renal allograft rejection. Ann Diagn Pathol 2002;6:122—4.Sako H., Nakane Y., Okino K. et al. Immunohistochemical study of the cells infiltrating human renal allografts by theABC and the IGSS method using monoclonal antibodies. Transplantation 1987;44(1):43—50.Sako H., Nakane Y., Okino K. et al. Immunohistochemical study of the cells infiltrating human renal allografts by theABC and the IGSS method using monoclonal antibodies. Transplantation 1987;44(1):43—50.Mauiyyedi S ., Crespo M., Collins A.B. et al. Acute Humoral Rejection in Kidney Transplantation: II. Morphology, Immunopathology, and Pathologic Classification. J Am Soc Nephrol 2002;13:779—87.Mauiyyedi S ., Crespo M., Collins A.B. et al. Acute Humoral Rejection in Kidney Transplantation: II. Morphology, Immunopathology, and Pathologic Classification. J Am Soc Nephrol 2002;13:779—87.Rotmans S., Collins A.B., Colvin R.B. C4d deposition in allograft: current concepts and interpretation. Transplantation reviews 2005;19:65—77.Rotmans S., Collins A.B., Colvin R.B. C4d deposition in allograft: current concepts and interpretation. Transplantation reviews 2005;19:65—77.Herzenberg A.M., Gill J.S., Djurgev O. et al. C4d deposition in acute rejection: an independent long-term prognostic factor. J Am Soc Nephrol 2002;13:234—41.Herzenberg A.M., Gill J.S., Djurgev O. et al. C4d deposition in acute rejection: an independent long-term prognostic factor. J Am Soc Nephrol 2002;13:234—41.Habib R., Zurowska A, Hinglais A. A specific glomerular lesion of the graft — allograft glomerulopathy. Kidney Int 1993;44(suppl 42):104—11.Habib R., Zurowska A, Hinglais A. A specific glomerular lesion of the graft — allograft glomerulopathy. Kidney Int 1993;44(suppl 42):104—11.Mauiyyedi S., Pelle P.D., Saidman S. et al. Chronic Humoral Rejection: Identification of antibody-mediated chronic renal allograft rejection by C4d deposits in peritubular capillaries. J Am Soc Nephrol 2001;12:574—82.Mauiyyedi S., Pelle P.D., Saidman S. et al. Chronic Humoral Rejection: Identification of antibody-mediated chronic renal allograft rejection by C4d deposits in peritubular capillaries. J Am Soc Nephrol 2001;12:574—82.Nankivell B.J., Borrows R.J., Fung C.L. The natural history of chronic allograft nephropathy. N Engl J Med 2003;349:2326—33.Nankivell B.J., Borrows R.J., Fung C.L. The natural history of chronic allograft nephropathy. N Engl J Med 2003;349:2326—33.Sis B., Dadras F., Khoshjou F. et al. Reproducibility studies on arteriolar hyaline thickening scoring in calcineurin inhibitor-treated renal allograft recipients. Am J Transplant 2006;6:1444—50.Sis B., Dadras F., Khoshjou F. et al. Reproducibility studies on arteriolar hyaline thickening scoring in calcineurin inhibitor-treated renal allograft recipients. Am J Transplant 2006;6:1444—50.Hirsch H.H., Suthanthiran M. The natural history, risk factors and outcomes of polyomavirus BK-associated nephropathy after renal transplantation. Nat Clin Pract Nephrol 2006;2(5):240—1.Hirsch H.H., Suthanthiran M. The natural history, risk factors and outcomes of polyomavirus BK-associated nephropathy after renal transplantation. Nat Clin Pract Nephrol 2006;2(5):240—1.Viscount H.B., Eid A.J., Espy M.J. et al. Polyomavirus polymerase chain reaction as a surrogate marker of polyomavirus-associated nephropathy. Transplantation 2007;84:340—5.Viscount H.B., Eid A.J., Espy M.J. et al. Polyomavirus polymerase chain reaction as a surrogate marker of polyomavirus-associated nephropathy. Transplantation 2007;84:340—5.Drachenberg C.B., Papadimitriou J.C., Hirsch H.H. et al. Histological patterns of polyomavirus nephropathy: correlation with graft outcome and viral load. Am J Transplant 2004;4:2082—92.Drachenberg C.B., Papadimitriou J.C., Hirsch H.H. et al. Histological patterns of polyomavirus nephropathy: correlation with graft outcome and viral load. Am J Transplant 2004;4:2082—92.Hariharan S., Savin V.J. Recurrent and de novo disease after renal transplantation: a report from the Renal Allograft Disease Registry. Pediatr Transplant 2004;8(4):349—50.Hariharan S., Savin V.J. Recurrent and de novo disease after renal transplantation: a report from the Renal Allograft Disease Registry. Pediatr Transplant 2004;8(4):349—50.Ramos E.L., Тisher C.C. Recurrent diseasis in the kidney transplant. Am J Kidney Dis 1994;24:142.Ramos E.L., Тisher C.C. Recurrent diseasis in the kidney transplant. Am J Kidney Dis 1994;24:142.Floege I. Recurrent glomerulonephritis following renal transplantation: an update. NDT 2003;18:1260—5.Floege I. Recurrent glomerulonephritis following renal transplantation: an update. NDT 2003;18:1260—5.Ponticelli C., Traversi L., Banfi G. Renal transplantation in patients with IgA mesangial glomerulonephritis. Pediatr Transplant 2004;8:334—8.Ponticelli C., Traversi L., Banfi G. Renal transplantation in patients with IgA mesangial glomerulonephritis. Pediatr Transplant 2004;8:334—8.Abbott K.C., Sawyers E.S., Oliver J.D. III et al. Graft loss due to recurrent focal segmental glomerulosclerosis in renal transplant recipients in the United States. Am J Kidney Dis 2001;37:366—73.Abbott K.C., Sawyers E.S., Oliver J.D. III et al. Graft loss due to recurrent focal segmental glomerulosclerosis in renal transplant recipients in the United States. Am J Kidney Dis 2001;37:366—73.Tejani A., Stablein D.H. Recurrence of focal segmental glomerulosclerosis posttransplantation: a special report of the North American Pediatric Renal Transplant Cooperative Study. J Am Soc Nephrol 1992;2(suppl):258—63.Tejani A., Stablein D.H. Recurrence of focal segmental glomerulosclerosis posttransplantation: a special report of the North American Pediatric Renal Transplant Cooperative Study. J Am Soc Nephrol 1992;2(suppl):258—63.Hariharan S., Adams M.B., Brennan D.C. et al. Recurrent and de novo glomerular disease after renal transplantation. A report from the Renal Allograft Disease Registry (RADR). Transplantation 1999;68:635—41.Hariharan S., Adams M.B., Brennan D.C. et al. Recurrent and de novo glomerular disease after renal transplantation. A report from the Renal Allograft Disease Registry (RADR). Transplantation 1999;68:635—41.Savin V.J., 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;334:878—83.Savin V.J., 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;334:878—83.Andresdottir M.B., Assman K.J., Hojistma A.J. et al. Renal transplantation in patients with dense deposit disease: morphological characteristics of recurrent disease and clinical outcome. Nephrol Dial Transplant 1999;14:1723—31.Andresdottir M.B., Assman K.J., Hojistma A.J. et al. Renal transplantation in patients with dense deposit disease: morphological characteristics of recurrent disease and clinical outcome. Nephrol Dial Transplant 1999;14:1723—31.Couser W. Recurrent glomerulonephritis in the renal allograft: an update of selected areas. Exp Clin Transplant 2005;1:283—8.Couser W. Recurrent glomerulonephritis in the renal allograft: an update of selected areas. Exp Clin Transplant 2005;1:283—8.Hariharan S., Smith R.D., Viero R. et al. Diabetic nephropathy after renal transplantation. Transplantation 1996:62:632—5.Hariharan S., Smith R.D., Viero R. et al. Diabetic nephropathy after renal transplantation. Transplantation 1996:62:632—5.Bhalla V., Nast C.C., Stollenwerk N. et al. Recurrent and de novo diabetic nephropathy in renal allografts. Transplantation 2003;75:66—71.Bhalla V., Nast C.C., Stollenwerk N. et al. Recurrent and de novo diabetic nephropathy in renal allografts. Transplantation 2003;75:66—71.Truong L., Gelfand J., D'Agati V. et al. De novo membranous glomerulonephropathy in renal allografts: a report of 10 cases and review of the literature. Am J Kidney Dis 1989;14:131—44.Truong L., Gelfand J., D'Agati V. et al. De novo membranous glomerulonephropathy in renal allografts: a report of 10 cases and review of the literature. Am J Kidney Dis 1989;14:131—44.Byrne M.C., Budisavljevic M.N., Fanz Z. et al. Renal transplant in patients with Alport's syndrome. Am J Kidney Dis 2002;39:769—75.Byrne M.C., Budisavljevic M.N., Fanz Z. et al. Renal transplant in patients with Alport's syndrome. Am J Kidney Dis 2002;39:769—75.Querin S., Noel L.H., Grunfeld J.P. et al. Linear glomerular IgG fixation in renal allografts: Incidence and significance in Alport's syndrome. Clin Nephrol 1986;25:134—40.Querin S., Noel L.H., Grunfeld J.P. et al. Linear glomerular IgG fixation in renal allografts: Incidence and significance in Alport's syndrome. Clin Nephrol 1986;25:134—40.

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