Состояние проблемы моноклональной гаммапатии ренального значения (MGRS) на современном этапе: вопросы терминологии, диагностики и лечения
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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
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Ключевые слова: моноклональная гаммапатия ренального значения, амилоидоз, болезнь моноклональных иммуноглобулиновых депозитов.
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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.
Keywords: amyloidosis, monoclonal gammopathy of renal significance, monoclonal immunoglobulin deposition disease.
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
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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
ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
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L.V. Lysenko (Kozlovskaya), V.V. Rameev, T.V. Androsova
Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia