切换至 "中华医学电子期刊资源库"

中华肾病研究电子杂志 ›› 2015, Vol. 04 ›› Issue (05) : 236 -240. doi: 10.3877/cma.j.issn.2095-3216.2015.05.004

所属专题: 文献

专家论坛

轻链沉积病肾损害的诊断与治疗
林珊1,(), 贾俊亚1   
  1. 1. 300052 天津医科大学总医院肾内科
  • 出版日期:2015-10-28
  • 通信作者: 林珊
  • 基金资助:
    国家自然科学基金(81270791); 天津市卫生局重点攻关课题(11KG132); 天津市应用基础及前沿计划(14JCYBJC27900)

Diagnosis and treatment of light chain deposition disease with renal involvement

Shan Lin1,(), Junya Jia1   

  1. 1. Department of Nephrology, Tianjin Medical University General Hospital, Tianjin 300052, China
  • Published:2015-10-28
  • Corresponding author: Shan Lin
  • About author:
    Corresponding author: Lin Shan, Email:
引用本文:

林珊, 贾俊亚. 轻链沉积病肾损害的诊断与治疗[J]. 中华肾病研究电子杂志, 2015, 04(05): 236-240.

Shan Lin, Junya Jia. Diagnosis and treatment of light chain deposition disease with renal involvement[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2015, 04(05): 236-240.

轻链沉积病(LCDD)为单克隆免疫球蛋白轻链在肾脏、心脏、肝脏等组织的沉积。LCDD肾损害起病时多伴有慢性肾功能不全。典型的LCDD肾损害有相对特殊的临床表现,血、尿蛋白电泳及游离轻链定量有助于诊断,确诊需行肾组织病理学检查,包括光镜、荧光显微镜及电镜等检查。LCDD肾损害的治疗应综合考虑B细胞增殖程度和单克隆免疫球蛋白对肾功能造成的损害。应积极控制B细胞增殖,但治疗时应选择肾毒性较小的药物如硼替佐米,必要时改用大剂量马法兰+周围血干细胞移植(HDM/ASCT)方案。

Light chain deposition disease (LCDD), belonging to monoclonal gammopathy, refers to monoclonal immunoglobulin light chain deposition in kidney, heart, liver, and other tissues. Most LCDD patients with renal involvement at onset have chronic renal function insufficiency. Typical LCDD-related kidney damage presents relatively specific clinical manifestations. The serum or urine protein electrophoresis and quantitative analysis of free light chains are helpful in diagnosis of LCDD. LCDD-related kidney damage can be confirmed by light microscopy, fluorescence microscopy, and electron microscopy examinations. The treatment of LCDD-related renal impairment should be given in consideration of the degree of B cell proliferation and the renal function impairment caused by monoclonal immunoglobulins. B cell proliferation should be controlled actively with less toxic agents to the kidney such as bortezomib or, if necessary, with a high dose of melphalan plus peripheral blood stem cell transplantation (HDM/PBSCT) program.

图1 单克隆丙种球蛋白病(副蛋白血症)的构成
1
Bridoux F, Leung N, Hutchison CA, et al. Diagnosis of monoclonal gammopathy of renal significance [J]. Kidney Int, 2015, 87(4): 698-711.
2
Heher EC, Goes NB, Spitzer TR, et al. Kidney disease associated with plasma cell dyscrasias [J]. Blood, 2010, 116(9): 1397-1404.
3
Pozzi C, D′Amico M, Fogazzi GB, et al. Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors [J]. Am J Kidney Dis, 2003, 42(6): 1154-1163.
4
Hasegawa H. Aggregates, crystals, gels, and amyloids: intracellular and extracellular phenotypes at the crossroads of immunoglobulin physicochemical property and cell physiology [J]. Int J Cell Biol, 2013, 2013: 604867.
5
Ronco P, Plaisier E, Mougenot B, et al. Immunoglobulin light (heavy)-chain deposition disease: from molecular medicine to pathophysiology-driven therapy [J]. Clin J Am Soc Nephrol, 2006, 1(6): 1342-1350.
6
Sirac C, Bridoux F, Carrion C et al. Role of the monoclonal kappa chain V domain and reversibility of renal damage in a transgenic model of acquired Fanconi syndrome [J]. Blood, 2006, 108(3): 536-543.
7
Teng J, Turbat-Herrera EA, Herrera GA. An animal model of glomerular light-chain-associated amyloidogenesis depicts the crucial role of lysosomes [J]. Kidney Int, 2014, 86(4): 738-746.
8
Sirac C, Bridoux F. Mesangial cells as amyloid factory: a unique contribution of animal models [J]. Kidney Int, 2014, 86(4): 669-671.
9
Yadav P, Leung N, Sanders PW, et al. The use of immunoglobulin light chain assays in the diagnosis of paraprotein-related kidney disease [J]. Kidney Int, 2015, 87(4): 692-697.
10
Parry HM, Pratt G, Hutchison CA. Monoclonal gammopathy of undetermined significance: an update for nephrologists [J]. Adv Chronic Kidney Dis, 2012, 19(5): 291-296.
11
Dispenzieri A, Katzmann JA, Kyle RA, et al. Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study [J]. Lancet, 2010, 375(9727): 1721-1728.
12
Chang SH, Luo S, O′Brian KK, et al. Association between metformin use and transformation of monoclonal gammopathy of undetermined significance to multiple myeloma in U.S. veterans with diabetes mellitus: a population-based cohort study [J]. Lancet Haematol, 2015, 2(1): e30-e36.
13
Fermand JP, Bridoux F, Kyle RA, et al. How I treat monoclonal gammopathy of renal significance (MGRS) [J]. Blood, 2013, 122(22): 3583-3590.
14
Leung N, Bridoux F, Hutchison CA, et al. International Kidney and Monoclonal Gammopathy Research Group. Monoclonal gammopathy of renal significance: when MGUS is no longer undetermined or insignificant [J]. Blood, 2012, 120(22): 4292-4295.
15
Sicard A, Karras A, Goujon JM, et al. Light chain deposition disease without glomerular proteinuria: a diagnostic challenge for the nephrologist [J]. Nephrol Dial Transplant, 2014, 29(10): 1894-1902.
16
Melmed GM, Fenves AZ, Stone MJ. Urinary findings in renal light chain-derived amyloidosis and light chain deposition disease [J]. Clin Lymphoma Myeloma, 2009, 9(3): 234-238.
17
McTaggart MP, Lindsay J, Kearney EM. Replacing urine protein electrophoresis with serum free light chain analysis as a first-line test for detecting plasma cell disorders offers increased diagnostic accuracy and potential health benefit to patients [J]. Am J Clin Pathol, 2013, 140(6): 890-897.
18
Jenner E. Serum free light chains in clinical laboratory diagnostics [J]. Clin Chim Acta, 2014, 427: 15-20.
19
Colombat M, Holifanjaniaina S, Guillonneau F, et al. Mass spectrometry-based proteomic analysis: a good diagnostic tool for cystic lung light chain deposition disease [J]. Am J Respir Crit Care Med, 2013, 188(3): 404-405.
20
Gerth J, Busch M, Ott U, et al. Evolution of light chain deposition disease over 8 years [J]. Clin Nephrol, 2009, 72(5): 397-401.
21
Gharwan H, Truica CI. Bortezomib-based chemotherapy for light chain deposition disease presenting as acute renal failure [J]. Med Oncol, 2012, 29(2): 1197-1201.
22
Hutchison CA, Cockwell P, Stringer S. Early reduction of serum-Free light chains associates with renal recovery in myeloma kidney [J]. J Am Soc Nephrol, 2011, 22(6): 1129-1136.
23
Weber N, Mollee P, Augustson B, et al. Management of systemic AL amyloidosis: recommendations of the Myeloma Foundation of Australia Medical and Scientific Advisory Group [J]. Intern Med J, 2015, 45(4): 371-382.
24
Lorenz EC, Gertz MA, Fervenza FC, et al. Long-term outcome of autologous stem cell transplantation in light chain deposition disease [J]. Nephrol Dial Transplant, 2008, 23(6): 2052-2057.
25
Jimenez-Zepeda VH. Light chain deposition disease: novel biological insights and treatment advances [J]. Int J Lab Hematol, 2012, 34(4): 347-355.
26
Royer B, Arnulf B, Martinez F, et al. High dose chemotherapy in light chain or light and heavy chain deposition disease [J]. Kidney Int, 2004, 65(2): 642-648.
27
Telio D, Shepherd J, Forrest D, et al. High-dose melphalan followed by auto-SCT has favorable safety and efficacy in selected patients with light chain deposition disease and light and heavy chain deposition disease [J]. Bone Marrow Transplant, 2012, 47(3): 453-455.
28
Kastritis E, Migkou M, Gavriatopoulou M, et al. Treatment of light chain deposition disease with bortezomib and dexamethasone[J]. Haematologica, 2009, 94(2): 300-302.
29
Gharwan H, Truica CI. Bortezomib-based chemotherapy for light chain deposition disease presenting as acute renal failure [J]. Med Oncol, 2012, 29(2): 1197-1201.
30
Petrakis I, Stylianou K, Mavroeidi V, et al. Biopsy-proven resolution of renal light-chain deposition disease after autologous stem cell transplantation [J]. Nephrol Dial Transplant, 2010, 25(6): 2020-2023.
31
Tovar N, Cibeira MT, Rosiñol L, et al. Bortezomib/dexamethasone followed by autologous stem cell transplantation as front line treatment for light-chain deposition disease [J]. Eur J Haematol, 2012, 89(4): 340-344.
32
Tsakiris DJ, Stel VS, Finne P, et al. Incidence and outcome of patients starting renal replacement therapy for end-stage renal disease due to multiple myeloma or light-chain deposit disease: an ERA-EDTA Registry study [J]. Nephrol Dial Transplant, 2010, 25(4): 1200-1206.
33
Cohen C, Royer B, Javaugue V, et al. Bortezomib produces high hematological response rates with prolonged renal survival in monoclonal immunoglobulin deposition disease [J]. Kidney Int, 2015, doi: 10.1038/ki.2015.201. [Epub ahead of print].
[1] 何静松, 张恩帆, 赵毅, 杨杨, 何冬花, 韩晓雁, 郑高锋, 陈晶晶, 罗依, 施继敏, 黄河, 蔡真. 自体造血干细胞移植治疗髓外多发性骨髓瘤疗效分析[J]. 中华移植杂志(电子版), 2021, 15(02): 93-100.
[2] 谢彩蝶, 毛慧娟. 新型生物制剂在肾脏病治疗中的应用进展[J]. 中华肾病研究电子杂志, 2020, 09(05): 224-227.
[3] 苏杰, 杨小静, 周雪. HSP27介导多发性骨髓瘤细胞诱导硼替佐米耐药的机制研究[J]. 中华临床医师杂志(电子版), 2021, 15(10): 779-784.
[4] 余钰玲, 尚倩雯, 陈宁宁, 涂三芳. 转录因子核因子-kappa B抑制剂硼替佐米防治移植物抗宿主病的研究进展[J]. 中华临床医师杂志(电子版), 2018, 12(01): 49-52.
阅读次数
全文


摘要