Blood Res.  2024;59:28. 10.1007/s44313-024-00027-5.

Monoclonal gammopathy of renal significance from the perspective of nephrologists

Affiliations
  • 1Division of Nephrology, Hyonam Kidney Laboratory, Soonchunhyang University Hospital, 59 Daesagwan‑Ro, Yongsan‑Gu, Seoul, South Korea

Abstract

Kidney disease is a frequent complication of multiple myeloma and other malignancies associated with monoclonal gammopathies. Additionally, dysproteinemia-related kidney disease can occur independently of overt multiple myeloma or hematologic malignancies. Monoclonal gammopathy of renal significance (MGRS) is a spectrum of disorders in which a monoclonal immunoglobulin produced by a benign or premalignant B-cell or plasma cell clone causes kidney damage. MGRS-associated renal disease manifests in various forms, including immunoglobulin-associated amyloidosis, monoclonal immunoglobulin deposition diseases (light chain, heavy chain, and combined light and heavy chain deposition diseases), proliferative glomerulonephritis with monoclonal immunoglobulin deposits, C3 glomerulopathy with monoclonal gammopathy, and light chain proximal tubulopathy. Although MGRS is a nonmalignant or premalignant hematologic condition, it has significant renal implications that often lead to progressive kidney damage and, eventually, end-stage kidney disease. This review discusses the epidemiology, pathogenesis, and management of MGRS and focuses on the perspective of nephrologists.

Keyword

Chronic kidney disease; Kidney biopsy; Light chain; Monoclonal gammopathy

Reference

1. Heher EC, et al. 2013; Kidney disease and multiple myeloma. Clin J Am Soc Nephrol. 8(11):2007–17. DOI: 10.2215/CJN.12231212. PMID: 23868898. PMCID: PMC3817918.
2. Fermand JP, et al. 2018; Monoclonal gammopathy of clinical significance: a novel concept with therapeutic implications. Blood. 132(14):1478–85. DOI: 10.1182/blood-2018-04-839480. PMID: 30012636.
3. Crawford J, Eye MK, Cohen HJ. 1987; Evaluation of monoclonal gammopathies in the "well" elderly. Am J Med. 82(1):39–45. DOI: 10.1016/0002-9343(87)90375-5. PMID: 3492143.
4. Leung N, et al. 2019; The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group. Nat Rev Nephrol. 15(1):45–59. DOI: 10.1038/s41581-018-0077-4. PMID: 30510265. PMCID: PMC7136169.
5. Amaador K, et al. 2019; Monoclonal gammopathy of renal significance (MGRS) histopathologic classification, diagnostic workup, and therapeutic options. Neth J Med. 77(7):243–54. DOI: 10.1007/s11560-024-00772-9.
6. Bridoux F, et al. 2015; Diagnosis of monoclonal gammopathy of renal significance. Kidney Int. 87(4):698–711. DOI: 10.1038/ki.2014.408. PMID: 25607108.
7. Hong YA, et al. 2021; Trends in epidemiologic characteristics of end-stage renal disease from 2019 Korean Renal Data System (KORDS). Kidney Res Clin Pract. 40(1):52–61. DOI: 10.23876/j.krcp.20.202. PMID: 33789383. PMCID: PMC8041639. PMID: f3f8e1260db949db93ed56b7058973cc.
8. Organization, W.H. Ageing and health. 2022. Available from: https://www.who.int/news-room/fact-sheets/detail/ageing-and-health. 14 January 2024.
9. Doshi M, et al. 2016; Paraprotein-Related Kidney Disease: Kidney Injury from Paraproteins-What Determines the Site of Injury? Clin J Am Soc Nephrol. 11(12):2288–94. DOI: 10.2215/CJN.02560316. PMID: 27526707. PMCID: PMC5142058.
10. Sanders PW, Booker BB. 1992; Pathobiology of cast nephropathy from human Bence Jones proteins. J Clin Invest. 89(2):630–9. DOI: 10.1172/JCI115629. PMID: 1737851. PMCID: PMC442896.
11. Leung N, Bridoux F, Nasr SH. 2021; Monoclonal Gammopathy of Renal Significance. N Engl J Med. 384(20):1931–41. DOI: 10.1056/NEJMra1810907. PMID: 34010532.
12. Perazella MA, Finkel KW. 2016; Paraprotein-Related Kidney Disease: Attack of the Killer M Proteins. Clin J Am Soc Nephrol. 11(12):2256–9. DOI: 10.2215/CJN.02960316. PMID: 27927893. PMCID: PMC5142063.
13. Basnayake K, et al. 2011; The biology of immunoglobulin free light chains and kidney injury. Kidney Int. 79(12):1289–301. DOI: 10.1038/ki.2011.94. PMID: 21490587.
14. Myatt EA, et al. 1994; Pathogenic potential of human monoclonal immunoglobulin light chains: relationship of in vitro aggregation to in vivo organ deposition. Proc Natl Acad Sci U S A. 91(8):3034–8. DOI: 10.1073/pnas.91.8.3034. PMID: 8159701. PMCID: PMC43509.
15. Solomon A, Weiss DT, Kattine AA. 1991; Nephrotoxic potential of Bence Jones proteins. N Engl J Med. 324(26):1845–51. DOI: 10.1056/NEJM199106273242603. PMID: 1904132.
16. Teng J, et al. 2004; Different types of glomerulopathic light chains interact with mesangial cells using a common receptor but exhibit different intracellular trafficking patterns. Lab Invest. 84(4):440–51. DOI: 10.1038/labinvest.3700069. PMID: 14990980.
17. Merlini G, Bellotti V. 2003; Molecular mechanisms of amyloidosis. N Engl J Med. 349(6):583–96. DOI: 10.1056/NEJMra023144. PMID: 12904524.
18. Charitaki E, et al. 2016; Glomerular expression of matrix metalloproteinases in AL-amyloidosis and association with renal function at the time of kidney biopsy. Clin Nephrol. 85(1):44–54. DOI: 10.5414/CN108670. PMID: 26587779.
19. Jain A, et al. 2019; Pathophysiology and management of monoclonal gammopathy of renal significance. Blood Adv. 3(15):2409–23. DOI: 10.1182/bloodadvances.2019031914. PMID: 31409583. PMCID: PMC6693003.
20. Chauvet S, et al. 2017; Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy-associated C3 glomerulopathy. Blood. 129(11):1437–47. DOI: 10.1182/blood-2016-08-737163. PMID: 28069603.
21. Chauvet S, et al. 2018; Both Monoclonal and Polyclonal Immunoglobulin Contingents Mediate Complement Activation in Monoclonal Gammopathy Associated-C3 Glomerulopathy. Front Immunol. 9:2260. DOI: 10.3389/fimmu.2018.02260. PMID: 30333829. PMCID: PMC6175995. PMID: 45a54c4cddee40a79d7bc8371976ec81.
22. Ravindran A, et al. 2017; Thrombotic microangiopathy associated with monoclonal gammopathy. Kidney Int. 91(3):691–8. DOI: 10.1016/j.kint.2016.09.045. PMID: 27998645.
23. Nasr SH, et al. 2009; Proliferative glomerulonephritis with monoclonal IgG deposits. J Am Soc Nephrol. 20(9):2055–64. DOI: 10.1681/ASN.2009010110. PMID: 19470674. PMCID: PMC2736767.
24. Gozzetti A, et al. 2022; Monoclonal gammopathy of renal significance (MGRS): Real-world data on outcomes and prognostic factors. Am J Hematol. 97(7):877–84. DOI: 10.1002/ajh.26566. PMID: 35389534. PMCID: PMC9324084.
25. Liu J, et al. 2022; Clinicopathologic characteristics and prognostic analysis of monoclonal gammopathy of renal significance (MGRS) in patients with IgM monoclonal gammopathy: a case series. Sci Rep. 12(1):16994. DOI: 10.1038/s41598-022-21152-0. PMID: 36216844. PMCID: PMC9551084. PMID: 38eb3616e61f45f5b6f2bd646e11d29b.
26. Khera A, et al. 2019; Long term outcomes in monoclonal gammopathy of renal significance. Br J Haematol. 186(5):706–16. DOI: 10.1111/bjh.15987. PMID: 31141168.
27. Sy-Go JPT, et al. 2023; Monoclonal Gammopathy and Its Association with Progression to Kidney Failure and Mortality in Patients with CKD. Clin J Am Soc Nephrol. 19(3):319–28. DOI: 10.2215/CJN.0000000000000358. PMID: 37948069.
28. Bhutani G, et al. 2015; Hematologic characteristics of proliferative glomerulonephritides with nonorganized monoclonal immunoglobulin deposits. Mayo Clin Proc. 90(5):587–96. DOI: 10.1016/j.mayocp.2015.01.024. PMID: 25939936.
29. Nasr SH, et al. 2012; Renal monoclonal immunoglobulin deposition disease: a report of 64 patients from a single institution. Clin J Am Soc Nephrol. 7(2):231–9. DOI: 10.2215/CJN.08640811. PMID: 22156754.
30. Debiec H, et al. 2012; Recurrent membranous nephropathy in an allograft caused by IgG3κ targeting the PLA2 receptor. J Am Soc Nephrol. 23(12):1949–54. DOI: 10.1681/ASN.2012060577. PMID: 23123401. PMCID: PMC3507371.
31. Borza DB, et al. 2005; Recurrent Goodpasture's disease secondary to a monoclonal IgA1-kappa antibody autoreactive with the alpha1/alpha2 chains of type IV collagen. Am J Kidney Dis. 45(2):397–406. DOI: 10.1053/j.ajkd.2004.09.029. PMID: 15685519.
32. Fish R, et al. 2010; The incidence of major hemorrhagic complications after renal biopsies in patients with monoclonal gammopathies. Clin J Am Soc Nephrol. 5(11):1977–80. DOI: 10.2215/CJN.00650110. PMID: 20651154. PMCID: PMC3001781.
33. Paueksakon P, et al. 2003; Monoclonal gammopathy: significance and possible causality in renal disease. Am J Kidney Dis. 42(1):87–95. DOI: 10.1016/S0272-6386(03)00412-8. PMID: 12830460.
34. Novak L, et al. 2004; AL-amyloidosis is underdiagnosed in renal biopsies. Nephrol Dial Transplant. 19(12):3050–3. DOI: 10.1093/ndt/gfh503. PMID: 15507480.
35. Herrera GA, Turbat-Herrera EA. 2010; Ultrastructural immunolabeling in the diagnosis of monoclonal light-and heavy-chain-related renal diseases. Ultrastruct Pathol. 34(3):161–73. DOI: 10.3109/01913121003672873. PMID: 20455664.
36. Sethi S, et al. 2010; Mass spectrometry-based proteomic diagnosis of renal immunoglobulin heavy chain amyloidosis. Clin J Am Soc Nephrol. 5(12):2180–7. DOI: 10.2215/CJN.02890310. PMID: 20876678. PMCID: PMC2994078.
37. Cho J, et al. 2022; Comparison of serum and urine free light chain analysis in clinical diagnosis. Blood Res. 57(4):284–9. DOI: 10.5045/br.2022.2022187. PMID: 36419240. PMCID: PMC9812726.
38. Anderson KC, et al. 2009; NCCN clinical practice guidelines in oncology: multiple myeloma. J Natl Compr Canc Netw. 7(9):908–42. DOI: 10.6004/jnccn.2009.0061. PMID: 19878637.
39. Dispenzieri A, et al. 2009; International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 23(2):215–24. DOI: 10.1038/leu.2008.307. PMID: 19020545.
40. Palladini G, et al. 2009; Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem. 55(3):499–504. DOI: 10.1373/clinchem.2008.117143. PMID: 19131635.
41. Fermand JP, et al. 2013; How I treat monoclonal gammopathy of renal significance (MGRS). Blood. 122(22):3583–90. DOI: 10.1182/blood-2013-05-495929. PMID: 24108460.
42. Outcomes, K.D.I.G. 2023. KDIGO 2023 clinical practice guideline for the evaluation and management of chronic kidney disease. Available from: https://kdigo.org/wp-content/uploads/2017/02/KDIGO-2023-CKD-Guideline-Public-Review-Draft_5-July-2023.pdf. 14 Janurary 2024.
43. Leung N, et al. 2004; Long-term outcome of renal transplantation in light-chain deposition disease. Am J Kidney Dis. 43(1):147–53. DOI: 10.1053/j.ajkd.2003.09.020. PMID: 14712438.
44. Said SM, et al. 2018; Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits is associated with high rate of early recurrence in the allograft. Kidney Int. 94(1):159–69. DOI: 10.1016/j.kint.2018.01.028. PMID: 29716794.
45. Heerspink HJL, et al. 2020; Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 383(15):1436–46. DOI: 10.1056/NEJMoa2024816. PMID: 32970396.
46. Herrington WG, et al. 2023; Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 388(2):117–27. DOI: 10.1056/NEJMoa2204233. PMID: 36331190. PMCID: PMC7614055.
47. Bakris GL, et al. 2020; Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 383(23):2219–29. DOI: 10.1056/NEJMoa2025845. PMID: 33264825.
48. Sprangers B, Hegenbart U, Wetzels JFM. 2023; Kidney Transplantation in Patients With Monoclonal Gammopathy of Renal Significance. Transplantation. 107(5):1056–68. DOI: 10.1097/TP.0000000000004443. PMID: 36584374.
49. Kuppachi S, Holanda D, Thomas CP. 2016; Light Chain Deposition Disease After Kidney Transplantation With Long Graft Survival: Case Report. Transplant Proc. 48(1):255–8. DOI: 10.1016/j.transproceed.2015.12.009. PMID: 26915878.
Full Text Links
  • BR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2025 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr