Состояние проблемы моноклональной гаммапатии ренального значения (MGRS) на современном этапе: вопросы терминологии, диагностики и лечения
Состояние проблемы моноклональной гаммапатии ренального значения (MGRS) на современном этапе: вопросы терминологии, диагностики и лечения
Лысенко (Козловская) Л.В., Рамеев В.В., Андросова Т.В. Состояние проблемы моноклональной гаммапатии ренального значения (MGRS) на современном этапе: вопросы терминологии, диагностики и лечения. Терапевтический архив. 2020; 92 (6): 15–22. DOI: 10.26442/00403660.2020.06.000666
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Lysenko (Kozlovskaya) L.V., Rameev V.V., Androsova T.V. Monoclonal gammapathy of renal significance (MGRS) at the current state: terminology, diagnosis and treatment. Therapeutic Archive. 2020; 92 (6): 15–22. DOI: 10.26442/00403660.2020.06.000666
Состояние проблемы моноклональной гаммапатии ренального значения (MGRS) на современном этапе: вопросы терминологии, диагностики и лечения
Лысенко (Козловская) Л.В., Рамеев В.В., Андросова Т.В. Состояние проблемы моноклональной гаммапатии ренального значения (MGRS) на современном этапе: вопросы терминологии, диагностики и лечения. Терапевтический архив. 2020; 92 (6): 15–22. DOI: 10.26442/00403660.2020.06.000666
________________________________________________
Lysenko (Kozlovskaya) L.V., Rameev V.V., Androsova T.V. Monoclonal gammapathy of renal significance (MGRS) at the current state: terminology, diagnosis and treatment. Therapeutic Archive. 2020; 92 (6): 15–22. DOI: 10.26442/00403660.2020.06.000666
В статье с современных позиций обсуждается проблема моноклональной гаммапатии ренального значения (Monoclonal Gammopathy of Renal Significance – MGRS) – вопросы терминологии, патогенеза, классификации, диагностики и лечения. Обозначены трудности идентификации патогенного клона клеток В-лимфоцитарной линии, синтезирующего нефротоксические парапротеины и возможные пути их преодоления. Приведены собственные данные о структуре почечных заболеваний среди 276 больных многопрофильного терапевтического стационара с выявленной моноклональной гаммапатией с преобладанием среди них системного AL-амилоидоза. На основании анализа результатов лечения 140 больных AL-амилоидозом современными схемами химиотерапии показано улучшение выживаемости пациентов после 2000 г. по сравнению с показателем выживаемости до 2000 г., когда эта терапия не проводилась. Обсуждены вопросы лечения больных неамилоидными нефропатиями, в частности ассоциированными с моноклональной гаммапатией пролиферативных гломерулонефритов. Указана необходимость мультидисциплинарного подхода к ведению этих пациентов.
In this article we discussed the current state of monoclonal gammapathy of renal significance (Monoclonal Gammopathy of Renal Significance – MGRS) and revealed problems of B-cell clone secreting nephrotoxic monoclonal immunoglobulin identification. We followed 276 patients with monoclonal gammapathy including patients with non-amyloid nephropathy. The majority of patients had systemic AL-amyloidosis. We established better survival of the treated patients with systemic AL-amyloidosis in comparison with retrospective untreated cohort. We considered current treatment of patients with non-amyloid nephropathy and focused on the crucial role of multidisciplinary approach in management of these patients.
1. Rajkumar SV, Dispenzieri A, Kyle RA. Monoclonal gammopathy of undetermined significance, Waldenström macroglobulinemia, AL amyloidosis, and related plasma cell disorders: Diagnosis and treatment. Mayo Clin Proc. 2006;81(5):693-703. doi: 10.4065/81.5.693
2. Fermand JP, Bridoux F, Dispenzieri A, et al. Monoclonal gammopathy of clinical significance: A novel concept with therapeutic implications. Blood. 2018;132(14):1478-85. doi: 10.1182/blood-2018-04-839480
3. Zingone A, Kuehl WM. Pathogenesis of monoclonal gammopathy of undetermined significance and progression to multiple myeloma. Semin Hematol. 2011;48(1):4-12. doi: 10.1053/j.seminhematol.2010.11.003
4. Kyle RA, Rajkumar SV. Monoclonal gammopathy of undetermined significance and smouldering multiple myeloma: Emphasis on risk factors for progression. Br J Haematol. 2007;139(5):730-43. doi: 10.1111/j.1365-2141.2007.06873.x
5. Leung N, Bridoux F, Batuman V, et al. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group. Nat Rev Nephrol. 2019;15(1). doi: 10.1038/s41581-018-0077-4
6. Смирнов А.В., Афанасьев Б.В., Поддубная И.В. и др. Моноклональная гаммапатия ренального значения: консенсус гематологов и нефрологов России по введению нозологии, диагностике и обоснованности клон-ориентированной терапии. Нефрология. 2019;23(6):9-28 [Smirnov AV, Afanasyev BV, Poddubnaya IV, et al. Monoclonal gammopathyof renal signifi cance: Consensus of hematologists and nephrologists of Russia on the establishment of nosology, diagnostic approach and rationale for clone specifi c treatment. Nephrology. 2019;23(6):9-28 (In Russ.)]. doi: 10.36485/1561-6274-2019-23-6-9-28
7. Steiner N, Göbel G, Suchecki P, et al. Monoclonal gammopathy of renal significance (MGRS) increases the risk for progression to multiple myeloma: An observational study of 2935 MGUS patients. Oncotarget. 2018;9(2):2344-56. doi: 10.18632/oncotarget.23412
8. Bridoux F, Leung N, Hutchison CA, et al. Diagnosis of monoclonal gammopathy of renal significance. Kidney Int. 2015;87(4):698-711. doi: 10.1038/ki.2014.408
9. Ravindran A, Fervenza FC, Smith RJH, Sethi S. C3 glomerulopathy associated with monoclonal Ig is a distinct subtype. Kidney Int. 2018;94(1):178-86. doi: 10.1016/j.kint.2018.01.037
10. Jain A, Haynes R, Kothari J, et al. Pathophysiology and management of monoclonal gammopathy of renal significance. Blood Adv. 2019;3(15):2409-23. doi: 10.1182/bloodadvances.2019031914
11. Gertz MA. Immunoglobulin light chain amyloidosis: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol. 2011;86(2):180-6. doi: 10.1002/ajh.21934
12. Kapoulas S, Raptis V, Papaioannou M. New aspects on the pathogenesis of renal disorders related to monoclonal gammopathies. Nephrol Ther. 2015;11(3):135-43. doi: 10.1016/j.nephro.2014.12.005
13. Лысенко Л.В., Чеботарева Н.В., Мрыхин Н.Н. и др. Значимость выявления моноклональной гаммапатии у больных нефрологического профиля. Нефрология. 2019;23(2):82-90 [Lysenko LB, Chebotareva NV, Mrykhin NN, et al. Determining of monoclonal gammopathy in nephrological patients. Nephrol. 2019;23(2):82-90 (In Russ.)]. doi: 10.24884/1561-6274-2019-23-2-82-90
14. Merlini G, Palladini G. Differential diagnosis of monoclonal gammopathy of undetermined significance. Hematology Am Soc Hematol Educ Program. 2012;2012:595-603. doi: 10.1182/asheducation.v2012.1.595.3798563
15. Knight GB, Gao L, Gragnani L, et al. Detection of WA B cells in HCV infection: A potential prognostic marker for cryoglobulinemic vasculitis and B cell malignancies. Arthritis Rheum. 2010;62:2152-9. doi: 10.1002/art.27490
16. Debiec H, Hanoy M, Francois A, et al. Recurrent membranous nephropathy in an allograft caused by IgG3k targeting the PLA2 receptor.
J Am Soc Nephrol. 2012;23(12):1949-54. doi: 10.1681/ASN.2012060577
17. Said SM, Cosio FG, Valeri AM, et al. Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits is associated with high rate of early recurrence in the allograft. Kidney Int. 2018;94(1):159-69. doi: 10.1016/j.kint.2018.01.028
18. Borza D-B. Autoepitopes and Alloepitopes of Type IV Collagen: Role in the Molecular Pathogenesis of Anti-GBM Antibody Glomerulonephritis. Nephron Exp Nephrol. 2007;106(2):e37-e43. doi: 10.1159/000101791
19. Dispenzieri A. POEMS syndrome: 2017 Update on diagnosis, risk stratification, and management. Am J Hematol. 2017;92(8):814-29. doi: 10.1002/ajh.24802
20. Li W, Lu Z-F, Man X-Y, et al. VEGF upregulates VEGF receptor-2 on human outer root sheath cells and stimulates proliferation through ERK pathway. Mol Biol Rep. 2012;39(9):8687-94. doi: 10.1007/s11033-012-1725-6
21. Katzmann JA, Kyle RA, Benson J, et al. Screening Panels for Detection of Monoclonal Gammopathies. Clin Chem. 2009;55(8):1517-22. doi: 10.1373/clinchem.2009.126664
22. Willrich MAV, Murray DL, Kyle RA. Laboratory testing for monoclonal gammopathies: Focus on monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Clin Biochem. 2018;51:38-47. doi: 10.1016/j.clinbiochem.2017.05.001
23. Vrana JA, Gamez JD, Madden BJ, et al. Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood. 2009;114(24):4957-9. doi: 10.1182/blood-2009-07-230722
24. Dasari S, Alexander MP, Vrana JA, et al. DnaJ heat shock protein family B member 9 is a novel biomarker for fibrillary GN. J Am Soc Nephrol. 2018;29(1):51-6. doi: 10.1681/ASN.2017030306
25. Nasr SH, Vrana JA, Dasari S, et al. DNAJB9 Is a Specific Immunohistochemical Marker for Fibrillary Glomerulonephritis. Kidney Int Reports. 2018;3(1):56-64. doi: 10.1016/j.ekir.2017.07.017
26. Chauvet S, Frémeaux-Bacchi V, Petitprez F, et al. Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy-associated C3 glomerulopathy. Blood. 2017;129(11):1437-47. doi: 10.1182/blood-2016-08-737163
27. Hogan JJ, Weiss BM. Bridging the divide: An onco-nephrologic approach to the monoclonal gammopathies of renal significance. Clin J Am Soc Nephrol. 2016;11(9):1681-91. doi: 10.2215/CJN.03160316
28. Nasr SH, Valeri AM, Cornell LD, et al. Renal Monoclonal Immunoglobulin Deposition Disease: A Report of 64 Patients from a Single Institution. Clin J Am Soc Nephrol. 2012;7(2):231-9. doi: 10.2215/CJN.08640811
29. Sayed RH, Wechalekar AD, Gilbertson JA, et al. Natural history and outcome of light chain deposition disease. Blood. 2015;126(26):2805-10. doi: 10.1182/blood-2015-07-658872
30. Gertz MA. Immunoglobulin light chain amyloidosis: 2018 Update on diagnosis, prognosis, and treatment. Am J Hematol. 2018;93(9):1169-80. doi: 10.1002/ajh.25149
31. Nasr SH, Satoskar A, Markowitz GS, et al. Proliferative glomerulonephritis with monoclonal IgG deposits. J Am Soc Nephrol. 2009;20(9):2055-64. doi: 10.1681/ASN.2009010110
32. Sethi S, Fervenza FC, Rajkumar SV. Spectrum of manifestations of monoclonal gammopathy-associated renal lesions. Curr Opin Nephrol Hypertens. 2016;25(2):127-37. doi: 10.1097/MNH.0000000000000201
33. Bhutani G, Nasr SH, Said SM, et al. Hematologic Characteristics of Proliferative Glomerulonephritides With Nonorganized Monoclonal Immunoglobulin Deposits. Mayo Clin Proc. 2015;90(5):587-96. doi: 10.1016/j.mayocp.2015.01.024
34. Fermand JP, Bridoux F, Kyle RA, et al. How I treat monoclonal gammopathy of renal significance (MGRS). Blood. 2013;122(22):3583-90. doi: 10.1182/blood-2013-05-495929
35. Kyle RA, Therneau TM, Dispenzieri A, et al. Immunoglobulin M Monoclonal Gammopathy of Undetermined Significance and Smoldering Waldenström Macroglobulinemia. Clin Lymphoma, Myeloma Leuk. 2013;13(2):184-6. doi: 10.1016/j.clml.2013.02.005
36. Sethi S, Rajkumar SV. Monoclonal Gammopathy–Associated Proliferative Glomerulonephritis. Mayo Clin Proc. 2013;88(11):1284-93. doi: 10.1016/j.mayocp.2013.08.002
37. Milani P, Merlini G, Palladini G. Novel Therapies in Light Chain Amyloidosis. Kidney Int Reports. 2017;3(3):530-41. doi: 10.1016/j.ekir.2017.11.017
38. Cohen C, Royer B, Javaugue V, et al. Bortezomib produces high hematological response rates with prolonged renal survival in monoclonal immunoglobulin deposition disease. Kidney Int. 2015;88(5):1135-43. doi: 10.1038/ki.2015.201
39. Vaxman I, Gertz M. Recent Advances in the Diagnosis, Risk Stratification, and Management of Systemic Light-Chain Amyloidosis. Acta Haematol. 2019;141(2):93-106. doi: 10.1159/000495455
40. Gupta N, Hanley MJ, Xia C, et al. Clinical Pharmacology of Ixazomib: The First Oral Proteasome Inhibitor. Clin Pharmacokinet. 2019;58(4):431-49. doi: 10.1007/s40262-018-0702-1
________________________________________________
1. Rajkumar SV, Dispenzieri A, Kyle RA. Monoclonal gammopathy of undetermined significance, Waldenström macroglobulinemia, AL amyloidosis, and related plasma cell disorders: Diagnosis and treatment. Mayo Clin Proc. 2006;81(5):693-703. doi: 10.4065/81.5.693
2. Fermand JP, Bridoux F, Dispenzieri A, et al. Monoclonal gammopathy of clinical significance: A novel concept with therapeutic implications. Blood. 2018;132(14):1478-85. doi: 10.1182/blood-2018-04-839480
3. Zingone A, Kuehl WM. Pathogenesis of monoclonal gammopathy of undetermined significance and progression to multiple myeloma. Semin Hematol. 2011;48(1):4-12. doi: 10.1053/j.seminhematol.2010.11.003
4. Kyle RA, Rajkumar SV. Monoclonal gammopathy of undetermined significance and smouldering multiple myeloma: Emphasis on risk factors for progression. Br J Haematol. 2007;139(5):730-43. doi: 10.1111/j.1365-2141.2007.06873.x
5. Leung N, Bridoux F, Batuman V, et al. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group. Nat Rev Nephrol. 2019;15(1). doi: 10.1038/s41581-018-0077-4
6. Smirnov AV, Afanasyev BV, Poddubnaya IV, et al. Monoclonal gammopathyof renal signifi cance: Consensus of hematologists and nephrologists of Russia on the establishment of nosology, diagnostic approach and rationale for clone specifi c treatment. Nephrology. 2019;23(6):9-28 (In Russ.) doi: 10.36485/1561-6274-2019-23-6-9-28
7. Steiner N, Göbel G, Suchecki P, et al. Monoclonal gammopathy of renal significance (MGRS) increases the risk for progression to multiple myeloma: An observational study of 2935 MGUS patients. Oncotarget. 2018;9(2):2344-56. doi: 10.18632/oncotarget.23412
8. Bridoux F, Leung N, Hutchison CA, et al. Diagnosis of monoclonal gammopathy of renal significance. Kidney Int. 2015;87(4):698-711. doi: 10.1038/ki.2014.408
9. Ravindran A, Fervenza FC, Smith RJH, Sethi S. C3 glomerulopathy associated with monoclonal Ig is a distinct subtype. Kidney Int. 2018;94(1):178-86. doi: 10.1016/j.kint.2018.01.037
10. Jain A, Haynes R, Kothari J, et al. Pathophysiology and management of monoclonal gammopathy of renal significance. Blood Adv. 2019;3(15):2409-23. doi: 10.1182/bloodadvances.2019031914
11. Gertz MA. Immunoglobulin light chain amyloidosis: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol. 2011;86(2):180-6. doi: 10.1002/ajh.21934
12. Kapoulas S, Raptis V, Papaioannou M. New aspects on the pathogenesis of renal disorders related to monoclonal gammopathies. Nephrol Ther. 2015;11(3):135-43. doi: 10.1016/j.nephro.2014.12.005
13. Лысенко Л.В., Чеботарева Н.В., Мрыхин Н.Н. и др. Значимость выявления моноклональной гаммапатии у больных нефрологического профиля. Нефрология. 2019;23(2):82-90 [Lysenko LB, Chebotareva NV, Mrykhin NN, et al. Determining of monoclonal gammopathy in nephrological patients. Nephrol. 2019;23(2):82-90 (In Russ.)]. doi: 10.24884/1561-6274-2019-23-2-82-90
14. Merlini G, Palladini G. Differential diagnosis of monoclonal gammopathy of undetermined significance. Hematology Am Soc Hematol Educ Program. 2012;2012:595-603. doi: 10.1182/asheducation.v2012.1.595.3798563
15. Knight GB, Gao L, Gragnani L, et al. Detection of WA B cells in HCV infection: A potential prognostic marker for cryoglobulinemic vasculitis and B cell malignancies. Arthritis Rheum. 2010;62:2152-9. doi: 10.1002/art.27490
16. Debiec H, Hanoy M, Francois A, et al. Recurrent membranous nephropathy in an allograft caused by IgG3k targeting the PLA2 receptor.
J Am Soc Nephrol. 2012;23(12):1949-54. doi: 10.1681/ASN.2012060577
17. Said SM, Cosio FG, Valeri AM, et al. Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits is associated with high rate of early recurrence in the allograft. Kidney Int. 2018;94(1):159-69. doi: 10.1016/j.kint.2018.01.028
18. Borza D-B. Autoepitopes and Alloepitopes of Type IV Collagen: Role in the Molecular Pathogenesis of Anti-GBM Antibody Glomerulonephritis. Nephron Exp Nephrol. 2007;106(2):e37-e43. doi: 10.1159/000101791
19. Dispenzieri A. POEMS syndrome: 2017 Update on diagnosis, risk stratification, and management. Am J Hematol. 2017;92(8):814-29. doi: 10.1002/ajh.24802
20. Li W, Lu Z-F, Man X-Y, et al. VEGF upregulates VEGF receptor-2 on human outer root sheath cells and stimulates proliferation through ERK pathway. Mol Biol Rep. 2012;39(9):8687-94. doi: 10.1007/s11033-012-1725-6
21. Katzmann JA, Kyle RA, Benson J, et al. Screening Panels for Detection of Monoclonal Gammopathies. Clin Chem. 2009;55(8):1517-22. doi: 10.1373/clinchem.2009.126664
22. Willrich MAV, Murray DL, Kyle RA. Laboratory testing for monoclonal gammopathies: Focus on monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Clin Biochem. 2018;51:38-47. doi: 10.1016/j.clinbiochem.2017.05.001
23. Vrana JA, Gamez JD, Madden BJ, et al. Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood. 2009;114(24):4957-9. doi: 10.1182/blood-2009-07-230722
24. Dasari S, Alexander MP, Vrana JA, et al. DnaJ heat shock protein family B member 9 is a novel biomarker for fibrillary GN. J Am Soc Nephrol. 2018;29(1):51-6. doi: 10.1681/ASN.2017030306
25. Nasr SH, Vrana JA, Dasari S, et al. DNAJB9 Is a Specific Immunohistochemical Marker for Fibrillary Glomerulonephritis. Kidney Int Reports. 2018;3(1):56-64. doi: 10.1016/j.ekir.2017.07.017
26. Chauvet S, Frémeaux-Bacchi V, Petitprez F, et al. Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy-associated C3 glomerulopathy. Blood. 2017;129(11):1437-47. doi: 10.1182/blood-2016-08-737163
27. Hogan JJ, Weiss BM. Bridging the divide: An onco-nephrologic approach to the monoclonal gammopathies of renal significance. Clin J Am Soc Nephrol. 2016;11(9):1681-91. doi: 10.2215/CJN.03160316
28. Nasr SH, Valeri AM, Cornell LD, et al. Renal Monoclonal Immunoglobulin Deposition Disease: A Report of 64 Patients from a Single Institution. Clin J Am Soc Nephrol. 2012;7(2):231-9. doi: 10.2215/CJN.08640811
29. Sayed RH, Wechalekar AD, Gilbertson JA, et al. Natural history and outcome of light chain deposition disease. Blood. 2015;126(26):2805-10. doi: 10.1182/blood-2015-07-658872
30. Gertz MA. Immunoglobulin light chain amyloidosis: 2018 Update on diagnosis, prognosis, and treatment. Am J Hematol. 2018;93(9):1169-80. doi: 10.1002/ajh.25149
31. Nasr SH, Satoskar A, Markowitz GS, et al. Proliferative glomerulonephritis with monoclonal IgG deposits. J Am Soc Nephrol. 2009;20(9):2055-64. doi: 10.1681/ASN.2009010110
32. Sethi S, Fervenza FC, Rajkumar SV. Spectrum of manifestations of monoclonal gammopathy-associated renal lesions. Curr Opin Nephrol Hypertens. 2016;25(2):127-37. doi: 10.1097/MNH.0000000000000201
33. Bhutani G, Nasr SH, Said SM, et al. Hematologic Characteristics of Proliferative Glomerulonephritides With Nonorganized Monoclonal Immunoglobulin Deposits. Mayo Clin Proc. 2015;90(5):587-96. doi: 10.1016/j.mayocp.2015.01.024
34. Fermand JP, Bridoux F, Kyle RA, et al. How I treat monoclonal gammopathy of renal significance (MGRS). Blood. 2013;122(22):3583-90. doi: 10.1182/blood-2013-05-495929
35. Kyle RA, Therneau TM, Dispenzieri A, et al. Immunoglobulin M Monoclonal Gammopathy of Undetermined Significance and Smoldering Waldenström Macroglobulinemia. Clin Lymphoma, Myeloma Leuk. 2013;13(2):184-6. doi: 10.1016/j.clml.2013.02.005
36. Sethi S, Rajkumar SV. Monoclonal Gammopathy–Associated Proliferative Glomerulonephritis. Mayo Clin Proc. 2013;88(11):1284-93. doi: 10.1016/j.mayocp.2013.08.002
37. Milani P, Merlini G, Palladini G. Novel Therapies in Light Chain Amyloidosis. Kidney Int Reports. 2017;3(3):530-41. doi: 10.1016/j.ekir.2017.11.017
38. Cohen C, Royer B, Javaugue V, et al. Bortezomib produces high hematological response rates with prolonged renal survival in monoclonal immunoglobulin deposition disease. Kidney Int. 2015;88(5):1135-43. doi: 10.1038/ki.2015.201
39. Vaxman I, Gertz M. Recent Advances in the Diagnosis, Risk Stratification, and Management of Systemic Light-Chain Amyloidosis. Acta Haematol. 2019;141(2):93-106. doi: 10.1159/000495455
40. Gupta N, Hanley MJ, Xia C, et al. Clinical Pharmacology of Ixazomib: The First Oral Proteasome Inhibitor. Clin Pharmacokinet. 2019;58(4):431-49. doi: 10.1007/s40262-018-0702-1