Морфологические и иммуногистохимические предикторы почечного ответа на терапию у пациентов с миеломной каст-нефропатией и острым повреждением почек с потребностью в диализе
Морфологические и иммуногистохимические предикторы почечного ответа на терапию у пациентов с миеломной каст-нефропатией и острым повреждением почек с потребностью в диализе
Рехтина И.Г., Казарина Е.В., Столяревич Е.С. и др. Морфологические и иммуногистохимические предикторы почечного ответа на терапию у пациентов с миеломной каст-нефропатией и острым повреждением почек с потребностью в диализе. Терапевтический архив. 2020; 92 (7): 63–69.
DOI: 10.26442/00403660.2020.07.000776
DOI: 10.26442/00403660.2020.07.000776
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Аннотация
Цель. Выявить морфологические и иммуногистохимические предикторы обратимости острого повреждения почек (ОПП) с потребностью в диализе у больных миеломной каст-нефропатией (МКН) на основании исследования биоптатов почек.
Материалы и методы. Проведено исследование нефробиоптатов 36 пациентов с МКН и 3-й стадией ОПП (AKIN, 2012) с потребностью в диализе. Исследование биоптатов выполняли полуколичественным и количественным методом с применением компьютерной морфометрии. Иммуногистохимически в клетках эпителия канальцев и интерстиции определяли экспрессию Е-кадгерина, виментина, α-гладкомышечного актина. Индукционная терапия 26 пациентам проводилась по бортезомибсодержащим программам, 10 больным использовали другие схемы. Сравнительный анализ морфологических изменений в нефробиоптатах в зависимости от почечного ответа выполнен у пациентов с достигнутой гематологической ремиссией.
Результаты. Улучшение функции почек наблюдалось только у пациентов с гематологическим ответом на терапию. Не выявлено различий в количестве склерозированных клубочков, белковых цилиндров, площади клеточной воспалительной инфильтрации, а также степени острого повреждения канальцев у пациентов с почечном ответом и без него. У больных с почечным ответом по сравнению с пациентами без улучшения функции почек площадь интерстициального фиброза меньше (соответственно 24,9 и 45,9%; р=0,001), а площадь экспрессии E-кадгерина больше (соответственно 15,9 и 7,1%; p=0,006). Фиброз интерстиция 40% и более и/или площадь экспрессии Е-кадгерина менее 10% от площади тубулоинтерстиция имеют неблагоприятное прогностическое значение в достижении почечного ответа при МКН.
Заключение. При площади фиброза интерстиция 40% и более и площади экспрессии Е-кадгерина менее 10% вероятность отсутствия почечного ответа составляет 93,3% (отношение шансов 24,5) даже при достижении гематологического ответа на индукционную терапию. Количество белковых цилиндров, распространенность острого повреждения канальцев и воспалительной инфильтрации интерстиция не имеют прогностического значения.
Ключевые слова: миеломная каст-нефропатия, острое повреждение почек, множественная миелома, морфометрия нефробиоптата.
Materials and methods. Renal pathological findings were studied in 36 patients with MCN and dialysis-dependent stage 3 AKI (AKIN, 2012). The study of biopsy samples was performed by a semi-quantitative and quantitative analysis using computer morphometry. The expression of E-cadherin, vimentin and α-smooth muscle actin was determined immunohistochemically in the tubular cells and interstitium. Induction therapy for 26 patients was carried out to bortezomib-based programs; in 10 patients other schemes were used. A comparative analysis of morphological changes in nephrobiopathy depending on the renal response was performed in patients with achieved hematologic remission.
Results. Improved renal function was observed only in patients with hematologic response to therapy. There were no differences in the number of sclerotic glomeruli, protein casts, the area of inflammatory interstitial infiltration, and the degree of acute tubular damage in patients with and without renal response. In patients with renal response compared with patients without improving renal function, the area of interstitial fibrosis was less (24.9% and 45.9%, respectively; p=0.001), and the area of E-cadherin expression was larger (15.9% and 7.1%, respectively; p=0.006). Interstitial fibrosis of 40% or more and/or the area of expression of E-cadherin less than 10% of the area of tubulo-interstitium have an unfavorable prognostic value in achieving a renal response in MCN.
Conclusion. If the interstitial fibrosis area is 40% or more and the expression area of E-cadherin is less than 10%, the probability of the absence of a renal response is 93.3% (OR=24.5) even when a hematological response to induction therapy is achieved. The number of protein casts, the prevalence of acute tubular damage and inflammatory interstitial infiltration have not prognostic value.
Keywords: myeloma cast nephropathy, acute kidney injury, multiple myeloma, nephrobiopathy morphometry.
Материалы и методы. Проведено исследование нефробиоптатов 36 пациентов с МКН и 3-й стадией ОПП (AKIN, 2012) с потребностью в диализе. Исследование биоптатов выполняли полуколичественным и количественным методом с применением компьютерной морфометрии. Иммуногистохимически в клетках эпителия канальцев и интерстиции определяли экспрессию Е-кадгерина, виментина, α-гладкомышечного актина. Индукционная терапия 26 пациентам проводилась по бортезомибсодержащим программам, 10 больным использовали другие схемы. Сравнительный анализ морфологических изменений в нефробиоптатах в зависимости от почечного ответа выполнен у пациентов с достигнутой гематологической ремиссией.
Результаты. Улучшение функции почек наблюдалось только у пациентов с гематологическим ответом на терапию. Не выявлено различий в количестве склерозированных клубочков, белковых цилиндров, площади клеточной воспалительной инфильтрации, а также степени острого повреждения канальцев у пациентов с почечном ответом и без него. У больных с почечным ответом по сравнению с пациентами без улучшения функции почек площадь интерстициального фиброза меньше (соответственно 24,9 и 45,9%; р=0,001), а площадь экспрессии E-кадгерина больше (соответственно 15,9 и 7,1%; p=0,006). Фиброз интерстиция 40% и более и/или площадь экспрессии Е-кадгерина менее 10% от площади тубулоинтерстиция имеют неблагоприятное прогностическое значение в достижении почечного ответа при МКН.
Заключение. При площади фиброза интерстиция 40% и более и площади экспрессии Е-кадгерина менее 10% вероятность отсутствия почечного ответа составляет 93,3% (отношение шансов 24,5) даже при достижении гематологического ответа на индукционную терапию. Количество белковых цилиндров, распространенность острого повреждения канальцев и воспалительной инфильтрации интерстиция не имеют прогностического значения.
Ключевые слова: миеломная каст-нефропатия, острое повреждение почек, множественная миелома, морфометрия нефробиоптата.
________________________________________________
Materials and methods. Renal pathological findings were studied in 36 patients with MCN and dialysis-dependent stage 3 AKI (AKIN, 2012). The study of biopsy samples was performed by a semi-quantitative and quantitative analysis using computer morphometry. The expression of E-cadherin, vimentin and α-smooth muscle actin was determined immunohistochemically in the tubular cells and interstitium. Induction therapy for 26 patients was carried out to bortezomib-based programs; in 10 patients other schemes were used. A comparative analysis of morphological changes in nephrobiopathy depending on the renal response was performed in patients with achieved hematologic remission.
Results. Improved renal function was observed only in patients with hematologic response to therapy. There were no differences in the number of sclerotic glomeruli, protein casts, the area of inflammatory interstitial infiltration, and the degree of acute tubular damage in patients with and without renal response. In patients with renal response compared with patients without improving renal function, the area of interstitial fibrosis was less (24.9% and 45.9%, respectively; p=0.001), and the area of E-cadherin expression was larger (15.9% and 7.1%, respectively; p=0.006). Interstitial fibrosis of 40% or more and/or the area of expression of E-cadherin less than 10% of the area of tubulo-interstitium have an unfavorable prognostic value in achieving a renal response in MCN.
Conclusion. If the interstitial fibrosis area is 40% or more and the expression area of E-cadherin is less than 10%, the probability of the absence of a renal response is 93.3% (OR=24.5) even when a hematological response to induction therapy is achieved. The number of protein casts, the prevalence of acute tubular damage and inflammatory interstitial infiltration have not prognostic value.
Keywords: myeloma cast nephropathy, acute kidney injury, multiple myeloma, nephrobiopathy morphometry.
Список литературы
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15. Bridoux F, Carron PL, Pegourie B, et al.; MYRE Study Group. Effect of High-Cutoff Hemodialysis vs Conventional Hemodialysis on Hemodialysis Independence among Patients with Myeloma Cast Nephropathy: A Randomized Clinical Trial. JAMA. 2017;318(21):2099-110. doi: 10.1001/jama.2017.17924
16. Chanan-Khan AA, Kaufman JL, Mehta J, et al. Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective study. Blood. 2007;109(6):2604-6. doi: 10.1182/blood-2006-09-046409
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doi: 10.35754/0234-5730-2019-64-3-283-296
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19. Ecotière L, Thierry A, Debiais-Delpech C, et al. Prognostic value of kidney biopsy in myeloma cast nephropathy: A retrospective study of 70 patients. Nephrol Dialys Transplant. 2016;31(1):64-72. doi: 10.1093/ndt/gfv283
20. Levey AS, Stevens LA, Schmid CH, et al.; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Int Med. 2009;150(9):604-12. doi: 10.7326/0003-4819-150-9-200905050-00006
21. Solez K, Colvin RB, Racusen LC, et al. Banff 07 Classification of Renal Allograft Pathology: Updates and Future Directions. Am J Transplant. 2008;8(4):753-60. doi: 10.1111/j.1600-6143.2008.02159.x
22. Cattran DC, Coppo R, Cook HT, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Intl. 2009;76(5):534-45. doi: 10.1038/ki.2009.243
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2. Dimopoulos MA, Sonneveld P, Leung N, et al. International Myeloma Working Group Recommendations for the Diagnosis and Management of Myeloma-Related Renal Impairment. J Clin Oncol. 2016;34(13):1544-57. doi: 10.1200/JCO.2015.65.0044
3. Bladé J, Fernández-Llama P, Bosch F, et al. Renal failure in multiple myeloma: Presenting features and predictors of outcome in 94 patients from a single institution. Arch Int Med. 1998;158(17):1889-93. doi: 10.1001/archinte.158.17.1889
4. Yadav P, Cook M, Cockwell P. Current Trends of Renal Impairment in Multiple Myeloma. Kidney Dis. 2016;1(4):241-57. doi: 10.1159/000442511
5. Mendeleeva LP, Solovev MV, Alexeeva A, et al. Multiple Myeloma in Russia (First Results of the Registration Trial). Blood. 2017;130(Suppl. 1):5408.
6. Rekhtina IG, Mendeleeva LP, Biryukova LS. Dialysis-dependent renal failure in patients with multiple myeloma: Reversibility factors. Terapevticheskij Arhiv. 2015;87(7):72 (In Russ.) doi: 10.17116/terarkh201587772-76
7. Ying WZ, Wang PX, Sanders PW. Pivotal role of apoptosis signal-regulating kinase 1 in monoclonal free light chain-mediated apoptosis. Am J Pathol. 2012;180(1):41-7. doi: 10.1016/j.ajpath.2011.09.017
8. Hertig A, Bonnard G, Ulinski T, et al. Tubular nuclear accumulation of Snail and epithelial phenotypic changes in human myeloma cast nephropathy. Human Pathol. 2011;42(8):1142-8. doi: 10.1016/j.humpath.2010.11.006
9. Rekhtina IG, Mendeleeva LP, Varlamova EYu, Biryukova LS. Comparison of the efficiency of bortezomib-based protocols in induction of an early hematological and renal response in myeloma nephropathy patients with hemodialysis-dependent renal failure. Gematologiya i transfuziologiya. 2015;60(4):4-7 (In Russ.)
10. Ludwig H, Adam Z, Hajek R, et al. Light chain-induced acute renal failure can be reversed by bortezomib-doxorubicin-dexamethasone in multiple myeloma: results of a phase II study. J Clin Oncol. 2010;28(30):4635-41. doi: 10.1200/JCO.2010.28.1238
11. Ludwig H, Rauch E, Kuehr T, et al. Lenalidomide and dexamethasone for acute light chain-induced renal failure: a phase II study. Haematologica. 2015;100(3):385-91. doi: 10.3324/haematol.2014.115204
12. Dimopoulos MA, Roussou M, Gkotzamanidou M, et al. The role of novel agents on the reversibility of renal impairment in newly diagnosed symptomatic patients with multiple myeloma. Leukemia. 2013;27(2):423-9. doi: 10.1038/leu.2012.182
13. Rekhtina IG, Kazarina EV, Stolyarevich ES, et al. Interstitial fibrosis and outcomes of acute kidney injury in myeloma cast nephropathy. Nefrologiya i dializ. 2019;21(3):312-9 (In Russ.) doi: 10.28996/2618-9801-2019-3-312-319
14. Hutchison CA, Bladé J, Cockwell P, et al.; International Kidney and Monoclonal Gammopathy Research Group. Novel approaches for reducing free light chains in patients with myeloma kidney. Nat RevNephrol. 2012;8(4):234-43. doi: 10.1038/nrneph.2012.14
15. Bridoux F, Carron PL, Pegourie B, et al.; MYRE Study Group. Effect of High-Cutoff Hemodialysis vs Conventional Hemodialysis on Hemodialysis Independence among Patients with Myeloma Cast Nephropathy: A Randomized Clinical Trial. JAMA. 2017;318(21):2099-110. doi: 10.1001/jama.2017.17924
16. Chanan-Khan AA, Kaufman JL, Mehta J, et al. Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective study. Blood. 2007;109(6):2604-6. doi: 10.1182/blood-2006-09-046409
17. Semochkin SV, Zhelnova EI, Misyurina EN, et al. Сlinical importance of renal recover on outcomes of newly diagnosed multiple myeloma patients with severe and dialysis-dependent kidney failure. Gematologiya i transfuziologiya. 2019;64(3):283-96 (In Russ.) doi: 10.35754/0234-5730-2019-64-3-283-296
18. KDIGO. Kidney Disease: Improving Global Outcomes. CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3(1):339. doi: 10.1038/kisup.2012.48
19. Ecotière L, Thierry A, Debiais-Delpech C, et al. Prognostic value of kidney biopsy in myeloma cast nephropathy: A retrospective study of 70 patients. Nephrol Dialys Transplant. 2016;31(1):64-72. doi: 10.1093/ndt/gfv283
20. Levey AS, Stevens LA, Schmid CH, et al.; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Int Med. 2009;150(9):604-12. doi: 10.7326/0003-4819-150-9-200905050-00006
21. Solez K, Colvin RB, Racusen LC, et al. Banff 07 Classification of Renal Allograft Pathology: Updates and Future Directions. Am J Transplant. 2008;8(4):753-60. doi: 10.1111/j.1600-6143.2008.02159.x
22. Cattran DC, Coppo R, Cook HT, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Intl. 2009;76(5):534-45. doi: 10.1038/ki.2009.243
23. Ryan MT. Supplemental Digital Content. Health Phys. 2013;104(5):453. doi: 10.1097/HP.0b013e318287c86c
24. Kazarina EV, Rekhtina IG, Stolyarevich ES, et al. Method for determining intensity of interstitial renal fibrosis in myelome nephropathy Patent RF na izobretenie №2686846/06.05.19 Byul. №13 (In Russ.) https://elibrary.ru/item.asp?id=37476505
25. Vongwiwatana A, Tasanarong A, Rayner DC, et al. Epithelial to mesenchymal transition during late deterioration of human kidney transplants: The role of tubular cells in fibrogenesis. Am J Transplant. 2005;5(6):1367-74. doi: 10.1111/j.1600-6143.2005.00843.x
26. Galichon P, Hertig A. Epithelial to mesenchymal transition as a biomarker in renal fibrosis: are we ready for the bedside? Fibrogen Tis Rep 2011;4 (1):11. doi: 10.1186/1755-1536-4-11
27. Basnayake K, Cheung CK, Sheaff M, et al. Differential progression of renal scarring and determinants of late renal recovery in sustained dialysis dependent acute kidney injury secondary to myeloma kidney.
J Clin Pathol. 2010;63(10):884-7. doi: 10.1136/jcp.2010.079236
28. Vansthertem D, Gossiaux A, Declèves AE, et al. Expression of nestin, vimentin, and NCAM by renal interstitial cells after ischemic tubular injury. J Biomed Biotechnol. 2010;2010:193259. doi: 10.1155/2010/193259
29. Chebotereva NV, Bobkova IH, Varshavskij VA, et al. The role of smooth muscle al-phaactin in development of renal fibrosis in patients with chronic glomerulonephritis. Terapevticheskij Arhiv. 2006;78(5):17-21 (In Russ.)
30. Burns WC, Thomas MC. The molecular mediators of type 2 epithelial to mesenchymal transition (EMT) and their role in renal pathophysiology. Exp Rev Mol Med 2010;12:e17. doi: 10.1017/S1462399410001481
31. Hertig A, Verine J, Mougenot B, et al. Risk factors for early epithelial to mesenchymal transition in renal grafts. Am J Transplant. 2006;6(12):2937-46. doi: 10.1111/j.1600-6143.2006.01559.x
2. Dimopoulos MA, Sonneveld P, Leung N, et al. International Myeloma Working Group Recommendations for the Diagnosis and Management of Myeloma-Related Renal Impairment. J Clin Oncol. 2016;34(13):1544-57. doi: 10.1200/JCO.2015.65.0044
3. Bladé J, Fernández-Llama P, Bosch F, et al. Renal failure in multiple myeloma: Presenting features and predictors of outcome in 94 patients from a single institution. Arch Int Med. 1998;158(17):1889-93. doi: 10.1001/archinte.158.17.1889
4. Yadav P, Cook M, Cockwell P. Current Trends of Renal Impairment in Multiple Myeloma. Kidney Dis. 2016;1(4):241-57. doi: 10.1159/000442511
5. Mendeleeva LP, Solovev MV, Alexeeva A, et al. Multiple Myeloma in Russia (First Results of the Registration Trial). Blood. 2017;130(Suppl. 1):5408.
6. Рехтина И.Г., Менделеева Л.П., Бирюкова Л.С. Диализзависимая почечная недостаточность у больных множественной миеломой: факторы обратимости. Терапевтический архив. 2015;87(7):72 [Rekhtina IG, Mendeleeva LP, Biryukova LS. Dialysis-dependent renal failure in patients with multiple myeloma: Reversibility factors. Terapevticheskij Arhiv. 2015;87(7):72 (In Russ.)]. doi: 10.17116/terarkh201587772-76
7. Ying WZ, Wang PX, Sanders PW. Pivotal role of apoptosis signal-regulating kinase 1 in monoclonal free light chain-mediated apoptosis. Am J Pathol. 2012;180(1):41-7.
doi: 10.1016/j.ajpath.2011.09.017
8. Hertig A, Bonnard G, Ulinski T, et al. Tubular nuclear accumulation of Snail and epithelial phenotypic changes in human myeloma cast nephropathy. Human Pathol. 2011;42(8):1142-8. doi: 10.1016/j.humpath.2010.11.006
9. Рехтина И.Г., Менделеева Л.П., Варламова Е.Ю., Бирюкова Л.С. Сравнение эффективности бортезомибсодержащих программ в достижении раннего гематологического и почечного ответа у больных миеломной нефропатией с диализзависимой почечной недостаточностью. Гематология и трансфузиология. 2015;60(4):4-7 [Rekhtina IG, Mendeleeva LP, Varlamova EYu, Biryukova LS. Comparison of the efficiency of bortezomib-based protocols in induction of an early hematological and renal response in myeloma nephropathy patients with hemodialysis-dependent renal failure. Gematologiya i transfuziologiya. 2015;60(4):4-7 (In Russ.)].
10. Ludwig H, Adam Z, Hajek R, et al. Light chain-induced acute renal failure can be reversed by bortezomib-doxorubicin-dexamethasone in multiple myeloma: results of a phase II study. J Clin Oncol. 2010;28(30):4635-41. doi: 10.1200/JCO.2010.28.1238
11. Ludwig H, Rauch E, Kuehr T, et al. Lenalidomide and dexamethasone for acute light chain-induced renal failure: a phase II study. Haematologica. 2015;100(3):385-91.
doi: 10.3324/haematol.2014.115204
12. Dimopoulos MA, Roussou M, Gkotzamanidou M, et al. The role of novel agents on the reversibility of renal impairment in newly diagnosed symptomatic patients with multiple myeloma. Leukemia. 2013;27(2):423-9. doi: 10.1038/leu.2012.182
13. Рехтина И.Г., Казарина Е.В., Столяревич Е.С. и др. Прогностическое значение фиброза интерстиция в нефробиоптате в обратимости острого почечного повреждения при цилиндровой нефропатии у пациентов с множественной миеломой. Нефрология и диализ. 2019;21(3):312-9 [Rekhtina IG, Kazarina EV, Stolyarevich ES, et al. Interstitial fibrosis and outcomes of acute kidney injury in myeloma cast nephropathy. Nefrologiya i dializ. 2019;21(3):312-9 (In Russ.)]. doi: 10.28996/2618-9801-2019-3-312-319
14. Hutchison CA, Bladé J, Cockwell P, et al.; International Kidney and Monoclonal Gammopathy Research Group. Novel approaches for reducing free light chains in patients with myeloma kidney. Nat RevNephrol. 2012;8(4):234-43.
doi: 10.1038/nrneph.2012.14
15. Bridoux F, Carron PL, Pegourie B, et al.; MYRE Study Group. Effect of High-Cutoff Hemodialysis vs Conventional Hemodialysis on Hemodialysis Independence among Patients with Myeloma Cast Nephropathy: A Randomized Clinical Trial. JAMA. 2017;318(21):2099-110. doi: 10.1001/jama.2017.17924
16. Chanan-Khan AA, Kaufman JL, Mehta J, et al. Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective study. Blood. 2007;109(6):2604-6. doi: 10.1182/blood-2006-09-046409
17. Семочкин С.В., Желнова Е.И., Мисюрина Е.Н. и др. Клиническое значение восстановления функции почек у больных впервые диагностированной множественной миеломой, осложненной тяжелой и диализ-зависимой почечной недостаточностью. Гематология и трансфузиология. 2019;64(3):283-96 [Semochkin SV, Zhelnova EI, Misyurina EN, et al. Сlinical importance of renal recover on outcomes of newly diagnosed multiple myeloma patients with severe and dialysis-dependent kidney failure. Gematologiya i transfuziologiya. 2019;64(3):283-96 (In Russ.)].
doi: 10.35754/0234-5730-2019-64-3-283-296
18. KDIGO. Kidney Disease: Improving Global Outcomes. CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3(1):339. doi: 10.1038/kisup.2012.48
19. Ecotière L, Thierry A, Debiais-Delpech C, et al. Prognostic value of kidney biopsy in myeloma cast nephropathy: A retrospective study of 70 patients. Nephrol Dialys Transplant. 2016;31(1):64-72. doi: 10.1093/ndt/gfv283
20. Levey AS, Stevens LA, Schmid CH, et al.; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Int Med. 2009;150(9):604-12. doi: 10.7326/0003-4819-150-9-200905050-00006
21. Solez K, Colvin RB, Racusen LC, et al. Banff 07 Classification of Renal Allograft Pathology: Updates and Future Directions. Am J Transplant. 2008;8(4):753-60. doi: 10.1111/j.1600-6143.2008.02159.x
22. Cattran DC, Coppo R, Cook HT, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Intl. 2009;76(5):534-45. doi: 10.1038/ki.2009.243
23. Ryan MT. Supplemental Digital Content. Health Phys. 2013;104(5):453.
doi: 10.1097/HP.0b013e318287c86c
24. Казарина Е.В., Рехтина И.Г., Столяревич Е.С. и др. Способ определения выраженности интерстициального фиброза почек при миеломной нефропатии. Патент РФ на изобретение №2686846/06.05.19 Бюл. №13 [Kazarina EV, Rekhtina IG, Stolyarevich ES, et al. Method for determining intensity of interstitial renal fibrosis in myelome nephropathy Patent RF na izobretenie №2686846/06.05.19 Byul. №13 (In Russ.)]. https://elibrary.ru/item.asp?id=37476505
25. Vongwiwatana A, Tasanarong A, Rayner DC, et al. Epithelial to mesenchymal transition during late deterioration of human kidney transplants: The role of tubular cells in fibrogenesis. Am J Transplant. 2005;5(6):1367-74. doi: 10.1111/j.1600-6143.2005.00843.x
26. Galichon P, Hertig A. Epithelial to mesenchymal transition as a biomarker in renal fibrosis: are we ready for the bedside? Fibrogen Tis Rep 2011;4 (1):11.
doi: 10.1186/1755-1536-4-11
27. Basnayake K, Cheung CK, Sheaff M, et al. Differential progression of renal scarring and determinants of late renal recovery in sustained dialysis dependent acute kidney injury secondary to myeloma kidney.
J Clin Pathol. 2010;63(10):884-7. doi: 10.1136/jcp.2010.079236
28. Vansthertem D, Gossiaux A, Declèves AE, et al. Expression of nestin, vimentin, and NCAM by renal interstitial cells after ischemic tubular injury. J Biomed Biotechnol. 2010;2010:193259. doi: 10.1155/2010/193259
29. Чеботерева Н.В., Бобкова И.H., Варшавский В.А. и др. Роль гладкомышечного α-актина в развитии фиброза почек у больных хроническим гломерулонефритом. Терапевтический архив. 2006;78(5):17-21 [Chebotereva NV, Bobkova IH, Varshavskij VA, et al. The role of smooth muscle al-phaactin in development of renal fibrosis in patients with chronic glomerulonephritis. Terapevticheskij Arhiv. 2006;78(5):17-21 (In Russ.)].
30. Burns WC, Thomas MC. The molecular mediators of type 2 epithelial to mesenchymal transition (EMT) and their role in renal pathophysiology. Exp Rev Mol Med 2010;12:e17. doi: 10.1017/S1462399410001481
31. Hertig A, Verine J, Mougenot B, et al. Risk factors for early epithelial to mesenchymal transition in renal grafts. Am J Transplant. 2006;6(12):2937-46. doi: 10.1111/j.1600-6143.2006.01559.x
________________________________________________
2. Dimopoulos MA, Sonneveld P, Leung N, et al. International Myeloma Working Group Recommendations for the Diagnosis and Management of Myeloma-Related Renal Impairment. J Clin Oncol. 2016;34(13):1544-57. doi: 10.1200/JCO.2015.65.0044
3. Bladé J, Fernández-Llama P, Bosch F, et al. Renal failure in multiple myeloma: Presenting features and predictors of outcome in 94 patients from a single institution. Arch Int Med. 1998;158(17):1889-93. doi: 10.1001/archinte.158.17.1889
4. Yadav P, Cook M, Cockwell P. Current Trends of Renal Impairment in Multiple Myeloma. Kidney Dis. 2016;1(4):241-57. doi: 10.1159/000442511
5. Mendeleeva LP, Solovev MV, Alexeeva A, et al. Multiple Myeloma in Russia (First Results of the Registration Trial). Blood. 2017;130(Suppl. 1):5408.
6. Rekhtina IG, Mendeleeva LP, Biryukova LS. Dialysis-dependent renal failure in patients with multiple myeloma: Reversibility factors. Terapevticheskij Arhiv. 2015;87(7):72 (In Russ.) doi: 10.17116/terarkh201587772-76
7. Ying WZ, Wang PX, Sanders PW. Pivotal role of apoptosis signal-regulating kinase 1 in monoclonal free light chain-mediated apoptosis. Am J Pathol. 2012;180(1):41-7. doi: 10.1016/j.ajpath.2011.09.017
8. Hertig A, Bonnard G, Ulinski T, et al. Tubular nuclear accumulation of Snail and epithelial phenotypic changes in human myeloma cast nephropathy. Human Pathol. 2011;42(8):1142-8. doi: 10.1016/j.humpath.2010.11.006
9. Rekhtina IG, Mendeleeva LP, Varlamova EYu, Biryukova LS. Comparison of the efficiency of bortezomib-based protocols in induction of an early hematological and renal response in myeloma nephropathy patients with hemodialysis-dependent renal failure. Gematologiya i transfuziologiya. 2015;60(4):4-7 (In Russ.)
10. Ludwig H, Adam Z, Hajek R, et al. Light chain-induced acute renal failure can be reversed by bortezomib-doxorubicin-dexamethasone in multiple myeloma: results of a phase II study. J Clin Oncol. 2010;28(30):4635-41. doi: 10.1200/JCO.2010.28.1238
11. Ludwig H, Rauch E, Kuehr T, et al. Lenalidomide and dexamethasone for acute light chain-induced renal failure: a phase II study. Haematologica. 2015;100(3):385-91. doi: 10.3324/haematol.2014.115204
12. Dimopoulos MA, Roussou M, Gkotzamanidou M, et al. The role of novel agents on the reversibility of renal impairment in newly diagnosed symptomatic patients with multiple myeloma. Leukemia. 2013;27(2):423-9. doi: 10.1038/leu.2012.182
13. Rekhtina IG, Kazarina EV, Stolyarevich ES, et al. Interstitial fibrosis and outcomes of acute kidney injury in myeloma cast nephropathy. Nefrologiya i dializ. 2019;21(3):312-9 (In Russ.) doi: 10.28996/2618-9801-2019-3-312-319
14. Hutchison CA, Bladé J, Cockwell P, et al.; International Kidney and Monoclonal Gammopathy Research Group. Novel approaches for reducing free light chains in patients with myeloma kidney. Nat RevNephrol. 2012;8(4):234-43. doi: 10.1038/nrneph.2012.14
15. Bridoux F, Carron PL, Pegourie B, et al.; MYRE Study Group. Effect of High-Cutoff Hemodialysis vs Conventional Hemodialysis on Hemodialysis Independence among Patients with Myeloma Cast Nephropathy: A Randomized Clinical Trial. JAMA. 2017;318(21):2099-110. doi: 10.1001/jama.2017.17924
16. Chanan-Khan AA, Kaufman JL, Mehta J, et al. Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective study. Blood. 2007;109(6):2604-6. doi: 10.1182/blood-2006-09-046409
17. Semochkin SV, Zhelnova EI, Misyurina EN, et al. Сlinical importance of renal recover on outcomes of newly diagnosed multiple myeloma patients with severe and dialysis-dependent kidney failure. Gematologiya i transfuziologiya. 2019;64(3):283-96 (In Russ.) doi: 10.35754/0234-5730-2019-64-3-283-296
18. KDIGO. Kidney Disease: Improving Global Outcomes. CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3(1):339. doi: 10.1038/kisup.2012.48
19. Ecotière L, Thierry A, Debiais-Delpech C, et al. Prognostic value of kidney biopsy in myeloma cast nephropathy: A retrospective study of 70 patients. Nephrol Dialys Transplant. 2016;31(1):64-72. doi: 10.1093/ndt/gfv283
20. Levey AS, Stevens LA, Schmid CH, et al.; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Int Med. 2009;150(9):604-12. doi: 10.7326/0003-4819-150-9-200905050-00006
21. Solez K, Colvin RB, Racusen LC, et al. Banff 07 Classification of Renal Allograft Pathology: Updates and Future Directions. Am J Transplant. 2008;8(4):753-60. doi: 10.1111/j.1600-6143.2008.02159.x
22. Cattran DC, Coppo R, Cook HT, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Intl. 2009;76(5):534-45. doi: 10.1038/ki.2009.243
23. Ryan MT. Supplemental Digital Content. Health Phys. 2013;104(5):453. doi: 10.1097/HP.0b013e318287c86c
24. Kazarina EV, Rekhtina IG, Stolyarevich ES, et al. Method for determining intensity of interstitial renal fibrosis in myelome nephropathy Patent RF na izobretenie №2686846/06.05.19 Byul. №13 (In Russ.) https://elibrary.ru/item.asp?id=37476505
25. Vongwiwatana A, Tasanarong A, Rayner DC, et al. Epithelial to mesenchymal transition during late deterioration of human kidney transplants: The role of tubular cells in fibrogenesis. Am J Transplant. 2005;5(6):1367-74. doi: 10.1111/j.1600-6143.2005.00843.x
26. Galichon P, Hertig A. Epithelial to mesenchymal transition as a biomarker in renal fibrosis: are we ready for the bedside? Fibrogen Tis Rep 2011;4 (1):11. doi: 10.1186/1755-1536-4-11
27. Basnayake K, Cheung CK, Sheaff M, et al. Differential progression of renal scarring and determinants of late renal recovery in sustained dialysis dependent acute kidney injury secondary to myeloma kidney.
J Clin Pathol. 2010;63(10):884-7. doi: 10.1136/jcp.2010.079236
28. Vansthertem D, Gossiaux A, Declèves AE, et al. Expression of nestin, vimentin, and NCAM by renal interstitial cells after ischemic tubular injury. J Biomed Biotechnol. 2010;2010:193259. doi: 10.1155/2010/193259
29. Chebotereva NV, Bobkova IH, Varshavskij VA, et al. The role of smooth muscle al-phaactin in development of renal fibrosis in patients with chronic glomerulonephritis. Terapevticheskij Arhiv. 2006;78(5):17-21 (In Russ.)
30. Burns WC, Thomas MC. The molecular mediators of type 2 epithelial to mesenchymal transition (EMT) and their role in renal pathophysiology. Exp Rev Mol Med 2010;12:e17. doi: 10.1017/S1462399410001481
31. Hertig A, Verine J, Mougenot B, et al. Risk factors for early epithelial to mesenchymal transition in renal grafts. Am J Transplant. 2006;6(12):2937-46. doi: 10.1111/j.1600-6143.2006.01559.x
Авторы
И.Г. Рехтина1, Е.В. Казарина1, Е.С. Столяревич2,3, А.М. Ковригина1,4, В.Н. Двирнык1, С.М. Куликов1, Л.П. Менделеева1
1 ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России, Москва, Россия;
2 ГБУЗ «Городская клиническая больница №52» Департамента здравоохранения г. Москвы, Москва, Россия;
3 ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия;
4 Федеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий ФМБА России, Москва, Россия
1 National Research Center for Hematology, Moscow, Russia;
2 Moscow City Nephrology Center, Moscow City Hospital 52, Moscow, Russia;
3 Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia;
4 Federal Research Clinical Center of Specialized Types of Medical Care and Medical Technologies, Moscow, Russia
1 ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России, Москва, Россия;
2 ГБУЗ «Городская клиническая больница №52» Департамента здравоохранения г. Москвы, Москва, Россия;
3 ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия;
4 Федеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий ФМБА России, Москва, Россия
________________________________________________
1 National Research Center for Hematology, Moscow, Russia;
2 Moscow City Nephrology Center, Moscow City Hospital 52, Moscow, Russia;
3 Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia;
4 Federal Research Clinical Center of Specialized Types of Medical Care and Medical Technologies, Moscow, Russia
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