Skip to main content
SpringerLink
Log in

Renal Diseases Associated With Multiple Myeloma and Related Plasma Cell Dyscrasias

  • Chapter
Biology and Management of Multiple Myeloma

Part of the book series: Current Clinical Oncology ((CCO))

  • 625 Accesses

Abstract

Multiple myeloma (MM), light- or heavy-chain deposition disease (LCDD/ HCDD), light- or heavy-chain-associated amyloidosis (AL/AH), and acquired Fanconi syndrome (AFS) represent a group of disorders characterized by the presence of monoclonal plasma cells in bone marrow and their homogeneous immunoglobulin products—i.e., M proteins—in serum, urine, or both (1–6). These immunoglobulin components can be nephrotoxic, as evidenced by their propensity to form pathologic deposits within the kidney (7–16). Furthermore, the relentless progression of this deposition eventually leads to organ failure and largely accounts for the poor prognoses of patients with these illnesses (17–21). Because of these factors, it is imperative that physicians are cognizant of the renal diseases associated with MM and related plasma cell dyscrasias, so that they may institute appropriate therapeutic measures, especially those that can reduce the production of the toxic immunoglobulins responsible for the devastating and ultimately fatal nature of there disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Gallo G, Picken M, Buxbaum J, Frangione B. The spectrum of monoclonal immunoglobulin deposition disease associated with immunocytic dyscrasias. Semin Hematol 1989; 26: 234–245.

    PubMed  CAS  Google Scholar 

  2. Dhodapkar MV, Merlini G, Solomon A. Biology and therapy of immunoglobulin deposition diseases. Hematol Oncol Clin North Am 1997; 11:89–110.

    Article  PubMed  CAS  Google Scholar 

  3. Buxbaum JN, Chuba JV, Hellman GC, Solomon A, Gallo GR. Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis. Am Intern Med 1990; 112:455–464.

    Article  CAS  Google Scholar 

  4. Buxbaum J. Mechanisms of disease: monoclonal immunoglobulin deposition. Amyloidosis, light chain deposition disease, and light and heavy chain deposition disease. Hematol Oncol Clin North Am 1992; 6:323–346.

    PubMed  CAS  Google Scholar 

  5. Buxbaum J, Gallo G. Nonamyloidotic monoclonal immunoglubulin deposition disease. Light-chain, heavy-chain, and light-and heavy-chain deposition diseases. Hematol Oncol Clin North Am 1999; 13:1235–1248.

    Article  PubMed  CAS  Google Scholar 

  6. Kambham N, Markowitz GS, Appel GB, Kleiner MJ, Aucouturier P, D’Agati VD. Heavy chain deposition disease: the disease spectrum. Am J Kidney Dis 1999; 33:954–962.

    Article  PubMed  CAS  Google Scholar 

  7. Misatti L, D’Amico G, Ponticelli C, eds. The Kidney in Plasma Cell Dyscrasias. Dordrecht, The Netherlands: Kluwer Academic Publishers, 1988.

    Google Scholar 

  8. Kyle RA. Monoclonal gammopathies and the kidney. Ann Rev Med 1989; 40:53–60.

    Article  PubMed  CAS  Google Scholar 

  9. Sanders PW, Herrera GA. Monoclonal immunoglobulin light chain-related renal diseases. Semin Nephrol 1993; 13:324–341.

    PubMed  CAS  Google Scholar 

  10. Cohen AH. The kidney in plasma cell dyscrasias: Bence-Jones cast nephropathy and light chain deposit disease. Am J Kidney Dis 1998; 32:529–532.

    Article  PubMed  CAS  Google Scholar 

  11. Herrera GA. Renal manifestations of plasma cell dyscrasias: an appraisal from the patient’s bedside to the research laboratory. Ann Diagn Pathol 2000; 4:174–200.

    Article  PubMed  CAS  Google Scholar 

  12. Lin J, Markowitz GS, Valeri AM, et al. Renal monoclonal immunoglobulin deposition disease: the disease spectrum. J Am Soc Nephrol 2001; 12:1482–1492.

    PubMed  CAS  Google Scholar 

  13. Pozzi C, Locatelli F. Kidney and liver involvement in monoclonal light chain disorders. Semin Nephrol 2002; 22:319–330.

    PubMed  CAS  Google Scholar 

  14. Shaver-Lewis MJ, Shah SV. The kidney in plasma cell disorders. In: Mehta J, Singhal, eds. Myeloma. London: Martin Dunitz, 2002:203–221.

    Google Scholar 

  15. Solomon A, Weiss DT, Herrera GA. Light-chain deposition disease. In: Mehta J, Singhal, eds. Myeloma. London: Martin Dunitz, 2002:507–518.

    Google Scholar 

  16. Gertz MA, Lacy MQ, Dispenzieri A. Immunoglobulin light chain amyloidosis and the kidney. Kidney Int 2002; 61:1–9.

    Article  PubMed  Google Scholar 

  17. Rota S, Mougenot B, Baudouin B, et al. Multiple myeloma and severe renal failure: a clinico-pathologic study of outcome and prognosis in 34 patients. Medicine 1987; 66:126–137.

    Article  PubMed  CAS  Google Scholar 

  18. Alexanian R, Barlogie B, Dixon D. Renal failure in multiple myeloma: pathogenesis and prognostic implications. Arch Intern Med 1990; 150:1693–1695.

    Article  PubMed  CAS  Google Scholar 

  19. Pozzi C, Fogazzi GB, Banfi G, Strom EH, Ponticelli C, Locatelli F. Renal disease and patient survival in light chain deposition disease. Clin Nephrol 1995; 43:281–287.

    PubMed  CAS  Google Scholar 

  20. Blade J, Fernandez-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 Intern Med 1998; 158:1889–1893.

    Article  PubMed  CAS  Google Scholar 

  21. Gertz MA, Kyle RA, Greipp PR. Response rates and survival in primary systemic amyloidosis. Blood 1991; 77:257–262.

    PubMed  CAS  Google Scholar 

  22. Eulitz M, Weiss DT, Solomon A. Immunoglobulin heavy-chain-associated amyloidosis. Proc Natl Acad Sci USA 1990; 87:6542–6546.

    Article  PubMed  CAS  Google Scholar 

  23. Solomon A, Weiss DT, Murphy C. Primary amyloidosis associated with a novel heavy-chain fragment (AH amyloidosis). Am J Hematol 1994; 45:171–176.

    Article  PubMed  CAS  Google Scholar 

  24. Mai HL, Sheikh-Hamad D, Herrera GA, Gu X, Truong LD. Immunoglobulin heavy chain can be amyloidogenic: morphologic characterization including immunoelectron microscopy Am J Surg Pathol 2003; 27:541–545.

    Article  PubMed  Google Scholar 

  25. Klein R, Jaenichen R, Zachau HG. Expressed human immunoglobulin kappa genes and their hypermutation. Eur J Immunol 1993; 23:3248–3262.

    Article  PubMed  CAS  Google Scholar 

  26. Kawasaki K, Minoshima S, Nakato E, et al. One-megabase sequence analysis of the human immunoglobulin lambda gene locus. Genome Res 1997; 7:250–261.

    Article  PubMed  CAS  Google Scholar 

  27. Solomon A, Weiss DT. Protein and host factors implicated in the pathogenesis of light-chain amyloidosis (AL amyloidosis). Amyloid: Int J Exp Clin Invest 1995; 2:269–279.

    CAS  Google Scholar 

  28. Buxbaum J. Aberrant immunoglobulin synthesis in light chain amyloidosis. Free light chain and light chain fragment production by human bone marrow cells in short-term tissue culture. J Clin Invest 1986; 78:798–806.

    Article  PubMed  CAS  Google Scholar 

  29. Stevens FJ, Solomon A, Schiffer M. Bence-Jones proteins: a powerful tool for the fundamental study of protein chemistry and pathophysiology. Biochemistry 1991; 30:6803–6805.

    Article  PubMed  CAS  Google Scholar 

  30. Solomon A, Waldmann TA, Fahey JL, McFarlane AS. Metabolism of Bence-Jones proteins. J Clin Invest 1964;43:103–117.

    Article  PubMed  CAS  Google Scholar 

  31. Waldmann TA, Strober W, Mogielnicki RP. The renal handling of low molecular weight proteins. II. Disorders of serum protein catabolism in patients with tubular proteinuria, the nephrotic syndrome, or uremia. J Clin Invest 1972; 51:2162–2174.

    Article  PubMed  CAS  Google Scholar 

  32. Coward RA, DeLamore IW, Mallick NP, Robinson EL. The importance of urinary immunoglobulin light chain isoelectric point (pi) in nephrotoxicity in multiple myeloma. Clin Sci (Lond) 1984; 66:229–232.

    CAS  Google Scholar 

  33. Bellotti V, Merlini G, Bucciarelli E, Perfetti V, Quaglini S, Ascari E. Relevance of class, molecular weight and isoelectric point in predicting human light chain amyloidogenicity. Br J Haematol 1990; 74:65–69.

    Article  PubMed  CAS  Google Scholar 

  34. Batuman V, Guan S. Receptor-mediated endocytosis of immunoglobulin light chains by renal proximal tubule cells. Am J Physiol 1997; 272:521–530.

    Google Scholar 

  35. Batuman V, Verroust PJ, Navar GL, et al. Myeloma light chains are ligands for cubulin (gp 280). Am J Physiol 1998; 275:246–254.

    Google Scholar 

  36. Sanders PW, Herrera GA, Galla JH. Human Bence-Jones protein toxicity in rat proximal tubule epithelium in vivo. Kidney Int 1987; 32:851–861.

    Article  PubMed  CAS  Google Scholar 

  37. Batuman V, Guan S, O’Donovan R, Puschett JB. Effect of myeloma light chains on phosphate and glucose transport in renal proximal tubule cells. Ren Physiol Biochem 1994; 17:294–300.

    PubMed  CAS  Google Scholar 

  38. Guan S, el-Dahr S, Dipp S, Batuman V. Inhibition of Na-K-ATPase activity and gene expression by a myeloma light chain in proximal tubule cells. J Invest Med 1999; 47:496–501.

    CAS  Google Scholar 

  39. Pote A, Zwizinski C, Simon EE, Meleg-Smith S, Batuman V. Cytotoxicity of myeloma light chains in cultured human kidney proximal tubule cells. Am J Kidney Dis 2000; 36:735–744.

    Article  PubMed  CAS  Google Scholar 

  40. Solomon A, Weiss DT, Kattine AA. Nephrotoxic potential of Bence-Jones proteins. N Engl J Med 1991;324:1845–1851.

    Article  PubMed  CAS  Google Scholar 

  41. Abe M, Goto T, Kosaka M, Wolfenbarger D, Weiss DT, Solomon A. Differences in kappa to lambda ((:() ratio of serum and urinary free light chains. Clin Exp Immunol 1998; 111: 457–462.

    Article  PubMed  CAS  Google Scholar 

  42. Solomon A, Frangione B, Franklin EC. Bence-Jones proteins and light chains of immunoglobulins. Preferential association of the V(VI subgroup of human light chains with amyloidosis AL. J Clin Invest 1982; 70:453–460.

    Article  PubMed  CAS  Google Scholar 

  43. Ozaki S, Abe M, Wolfenbarger D, Weiss DT, Solomon A. Preferential expression of human (-light-chain variable-region subgroups in multiple myeloma, AL amyloidosis, and Waldenstrom’s macroglobulinemia. Clin Immunol Immunopathol 1994; 71:183–189.

    Article  PubMed  CAS  Google Scholar 

  44. Comenzo RL, Wally J, Kica G, et al. Clonal immunoglobulin light chain variable region germline gene use in AL amyloidosis: association with dominant amyloid-related organ involvement and survival after stem cell transplantation. Br J Haematol 1999; 106:744–751.

    Article  PubMed  CAS  Google Scholar 

  45. Comenzo RL, Zhang Y, Martinez C, Osman K, Herrera GA. The tropisim of organ involvement in primary systemic amyloidosis: contributions of lg VL germ line gene use and clonal plasma cell burden. Blood 2001; 98:714–720.

    Article  PubMed  CAS  Google Scholar 

  46. Perfetti V, Casarini S, Palladini G, et al. Analysis of V (lambda)-J(lambda) expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambdalll) as an amyloid-associated germline gene segment. Blood 2002; 100:948–953.

    Article  PubMed  CAS  Google Scholar 

  47. Cogne M, Preud’homme JL, Bauwens M, Touchard G, Aucouturier P. Structure of a monoclonal kappa chain of the V kappa IV subgroup in the kidney and plasma cells in light chain deposition disease. J Clin Invest 1991; 87:2186–2190.

    Article  PubMed  CAS  Google Scholar 

  48. Denoroy L, Deret S, Aucouturier P. Overrepresentation of the V(IV subgroup in light chain deposition disease. Immunol Lett 1994; 42:63–66.

    Article  PubMed  CAS  Google Scholar 

  49. Rocca A, Khamlichi AA, Touchard G, et al. Sequences of V(I subgroup light chains in Fanconi’s syndrome. Light chain V region gene usage restriction and peculiarities in myeloma-associated Fanconi’s syndrome. J Immunol 1995; 155:3245–3252.

    PubMed  CAS  Google Scholar 

  50. Stevens FJ, Weiss DT, Solomon A. Structural bases of light chain-related pathology. In: Zanetti M, Capra JD, eds. The Antibodies. Vol. 5. Amsterdam: Harwood Academic Publishers, 1999; 175–208.

    Google Scholar 

  51. Hurle MR, Helms LR, Li L, Chan W, Wetzel R. A role for destabilizing amino acid replacements in light-chain amyloidosis. Proc Natl Acad Sci USA. 1994; 91:5446–5450.

    Article  PubMed  CAS  Google Scholar 

  52. Preud’homme JL, Aucouturier P, Touchard G, et al. Monoclonal immunoglobulin deposition disease (Randall type). Relationship with structural abnormalities of immunoglobulin chains. Kidney Int 1994; 46:965–972.

    Article  PubMed  Google Scholar 

  53. Stevens PW, Raffen R, Hanson DK, et al. Recombinant immunoglobulin variable domains generated from synthetic genes provide a system for in vitro characterization of light-chain amyloid proteins. Protein Sci 1995; 4:421–432.

    Article  PubMed  CAS  Google Scholar 

  54. Helms LR, Wetzel R. Specificity of abnormal assembly in immunoglobulin light chain deposition disease and amyloidosis. J Mol Biol 1996; 257:77–86.

    Article  PubMed  CAS  Google Scholar 

  55. Gallo G, Goni F, Boctor F, et al. Light chain cardiomyopathy. Structural analysis of the light chain tissue deposits. Am J Pathol 1996; 148:1397–1406.

    PubMed  CAS  Google Scholar 

  56. Bellotti V, Stoppini M, Mangione PP, et al. Structural and functional characterization of 3 human immunoglobulin kappa light chains with different pathological implications. Biochim Biophys Acta 1996; 1317:161–167.

    Article  PubMed  CAS  Google Scholar 

  57. Deret S, Chomilier J, Huang DB, Preud’homme JL, Stevens FJ, Aucouturier P. Molecular modeling of immunoglobulin light chains implicates hydrophobic residues in non-amyloid light chain deposition disease. Protein Eng 1997; 10:1191–1197.

    Article  PubMed  CAS  Google Scholar 

  58. Wetzel R. Domain stability in immunoglobulin light chain deposition disorders. Adv Protein Chem 1997; 50:183–242.

    Article  PubMed  CAS  Google Scholar 

  59. Raffen R, Dieckman LJ, Szpunar M, et al. Physicochemical consequences of amino acid variations that contribute to fibril formation by immunoglobulin light chains. Protein Sci 1999;8:509–517.

    Article  PubMed  CAS  Google Scholar 

  60. Pokkuluri PR, Solomon A, Weiss DT, Stevens FJ, Schiffer M. Tertiary structure of human X6light chains. Amyloid: Int J Exp Clin Invest 1999; 6:165–171.

    CAS  Google Scholar 

  61. Vidal R, Goni F, Stevens F, et al. Somatic mutations of the LI2a gene in V-kappa (1) light chain deposition disease: potential effects on aberrant protein conformation and deposition. Am J Pathol 1999; 155:2009–2017.

    Article  PubMed  CAS  Google Scholar 

  62. Wall J, Schell M, Murphy CL, Hrncic R, Stevens FJ, Solomon A. Thermodynamic instability of human X6light chains: correlation with fibrillogenicity. Biochemistry 1999; 38: 14101–14106.

    Article  PubMed  CAS  Google Scholar 

  63. Ionescu-Zanetti C, Khurana R, Gillespie JR, et al. Monitoring the assembly of Ig light-chain amyloid fibrils by atomic force microscopy. Proc Natl Acad Sci USA 1999; 96: 13175–13179.

    Article  PubMed  CAS  Google Scholar 

  64. Bellotti V, Mangione P, Merlini G. Review: immunoglobulin light chain amyloidosis—the archetype of structural and pathogenic variability. J Struct Biol 2000; 130:280–289.

    Article  PubMed  CAS  Google Scholar 

  65. Davis DP, Gallo G, Vogen SM, et al. Both the environment and somatic mutations govern the aggregation pathway of pathogenic immunoglobulin light chain. J Mol Biol 2001; 313:1021–1034.

    Article  PubMed  CAS  Google Scholar 

  66. Khurana R, Gillespie JR, Talapatra A, et al. Partially folded intermediates as critical precursors of light chain amyloid fibrils and amorphous aggregates. Biochemistry 2001; 40:3525–3535.

    Article  PubMed  CAS  Google Scholar 

  67. Stevens FJ. Four structural risk factors identify most fibril-forming kappa light chains. Amyloid: Int J Exp Clin Invest 2000; 7:200–211.

    CAS  Google Scholar 

  68. Omtvedt LA, Bailey D, Renouf DV, et al. Glycosylation of immunoglobulin light chains associated with amyloidosis. Amyloid: Int J Protein Folding Disord 2000; 7:227–244.

    Article  CAS  Google Scholar 

  69. Stevens FJ, Kisilevsky R. Immunoglobulin light chains, glycosaminoglycans, and amyloid. Cell Mol Life Sci 2000; 57:441–449.

    Article  PubMed  CAS  Google Scholar 

  70. Solomon A, Weiss DT, Murphy CL, Hrncic R, Wall JS, Schell M. Light chain-associated amyloid deposits comprised of a novel kappa constant domain. Proc Natl Acad Sci USA. 1998;95:9547–9551.

    Article  PubMed  CAS  Google Scholar 

  71. Engvig JP, Olson KE, Gislefoss RE, Sletten K, Wahlstrom O, Westermark P. Constant region of a kappa III immunoglobulin light chain as a major AL-amyloid protein. Scand J Immunol 1998; 48:92–98.

    Article  PubMed  CAS  Google Scholar 

  72. Buxbaum JN. Abnormal immunoglobulin synthesis in monoclonal immunoglobulin light chain and light and heavy chain deposition disease. Amyloid: Int J Protein Folding Disord 2001;8:84–93.

    Article  CAS  Google Scholar 

  73. Takeda S, Takazakura E, Haratake J, Hoshii Y. Light chain deposition disease detected by antisera to a variable region of the kappa 1 light chain subgroup. Nephron 1998; 80:162–165.

    Article  PubMed  CAS  Google Scholar 

  74. Herrera GA. Low molecular weight proteins and the kidney: physiologic and pathologic considerations. Ultrastruct Pathol 1994; 18:89–98.

    Article  PubMed  CAS  Google Scholar 

  75. Sanders PW, Herrera GA, Kirk KA, Old CW, Galla JH. Spectrum of glomerular and tubulointerstitial renal lesions associated with monotypical immunoglobulin light chain deposition. Lab Invest 1991; 64:527–537.

    PubMed  CAS  Google Scholar 

  76. Picken MM, Shen S. Immunoglobulin light chains and the kidney: an overview. Ultrastruct Pathol 1994; 18:105–112.

    Article  PubMed  CAS  Google Scholar 

  77. Herrera GA, Paul R, Turbat-Herrera EA, et al. Ultrastructural immunolabeling in the diagnosis of light chain-related renal disease. Pathol Immunopathol Res 1986; 5:170–187.

    Article  PubMed  CAS  Google Scholar 

  78. Silver MM, Hearn SA, Walton JC, Lines LA, Walley VM. Immunogold quantitation of immunoglobulin light chains in renal amyloidosis and kappa light chain nephropathy. Am J Pathol 1990; 136:997–1007.

    PubMed  CAS  Google Scholar 

  79. Herrera GA, Sanders PW, Reddy B V, Hasbargen JA, Hammond WS, Brooke JD. Ultrastructural immunolabeling: a unique diagnostic tool in monoclonal light chain-related renal diseases. Ultrastruct Pathol 1994; 18:401–416.

    Article  PubMed  CAS  Google Scholar 

  80. Sanders PW, Herrera GA, Lott RL, Galla JH. Morphologic alterations of the proximal tubules in light chain-related renal disease. Kidney Int 1988; 33:881–889.

    Article  PubMed  CAS  Google Scholar 

  81. Strom EH, Fogazzi GB, Banfi G, Pozzi C, Mihatsch MJ. Light chain deposition disease of the kidney. Morphological aspects in 24 patients. Virchows Arch 1994; 425:271–280.

    Article  PubMed  CAS  Google Scholar 

  82. Gallo GR, Feiner HD, Chuba JV, Beneck D, Marion P, Cohen DH. Characterization of tissue amyloid by immunofluorescence microscopy. Clin Immunol Immunopathol 1986; 39: 479–490.

    Article  PubMed  CAS  Google Scholar 

  83. Murphy CL, Eulitz M, Hrncic R, et al. Chemical typing of amyloid protein contained in formalin-fixed paraffin-embedded biopsy specimens. Am J Clin Pathol 2001; 116:135–142.

    Article  PubMed  CAS  Google Scholar 

  84. Ganeval D, Noel L-H, Preud’homme JL, Droz D, Grunfeld JP. Light-chain deposition disease: its relation with AL-type amyloidosis. Kidney Int 1984; 26:1–9.

    Article  PubMed  CAS  Google Scholar 

  85. Jacquot C, Saint-Andre JP, Touchard G, et al. Association of systemic light-chain deposition disease and amyloidosis: a report of three patients with renal involvement. Clin Nephrol 1985; 24:93–98.

    PubMed  CAS  Google Scholar 

  86. Smith NM, Malcom AJ. Simultaneous AL-type amyloid and light chain deposition disease in a liver biopsy: a case report. Histopathology 1986; 10:1057–1064.

    Article  PubMed  CAS  Google Scholar 

  87. Kaplan B, Vidal R, Kumar A, Ghiso J, Frangione B, Gallo G. Amino-terminal identity of co-existent amyloid and non-amyloid immunoglobulin kappa light chain deposits. A human disease to study alterations of protein conformation. Clin Exp Immunol 1997; 110:472–478.

    Article  PubMed  CAS  Google Scholar 

  88. Casiraghi MA, De Paoli A, Assi A, et al. Hepatic amyloidosis with light chain deposition disease. A rare association. Dig Liver Dis 2000; 32:795–798.

    Article  PubMed  CAS  Google Scholar 

  89. Clyne DH, Pollak VE. Renal handling and pathophysiology of Bence-Jones proteins. Contrib Nephrol 1981;24:78–87.

    PubMed  CAS  Google Scholar 

  90. Smolens P, Venkatachalam M, Stein JH. Myeloma kidney cast nephropathy in a rat model of multiple myeloma. Kidney Int 1983; 24:192–204.

    Article  PubMed  CAS  Google Scholar 

  91. Smolens P, Barnes JL, Stein JH. Effect of chronic administration of different Bence-Jones proteins on rat kidney. Kidney Int 1986; 30:874–882.

    Article  PubMed  CAS  Google Scholar 

  92. Myatt EA, Westholm FA, Weiss DT, Solomon A, Schiffer M, Stevens FJ. Pathogenic potential of human monoclonal immunoglobulin light chains: relationship of in vitro aggregation to in vivo organ deposition. Proc Natl Acad Sci USA 1994; 91:3034–3038.

    Article  PubMed  CAS  Google Scholar 

  93. Solomon A, Weiss DT, Williams TK. Experimental model of human light-chain-associated disease. Curr Top Microbiol Immunol 1992; 182:261–267.

    Article  PubMed  CAS  Google Scholar 

  94. Khamlichi AA, Rocca A, Touchard G, Aucouturier P, Preud’homme JL, Cogne M. Role of light chain variable region in myeloma with light chain deposition disease: evidence from an experimental model. Blood 1995; 86:3655–3659.

    PubMed  CAS  Google Scholar 

  95. Solomon A, Weiss DT, Pepys MB. Induction in mice of human light-chain-associated amyloidosis. Am J Pathol 1992; 140:629–637.

    PubMed  CAS  Google Scholar 

  96. Leboulleux M, Lelong B, Mougenot B, et al. Protease resistance and binding of Ig light chains in myeloma-associated tubulopathies. Kidney Int 1995; 48:72–79.

    Article  PubMed  CAS  Google Scholar 

  97. Sanders PW, Booker BB. Pathobiology of cast nephropathy from human Bence-Jones proteins. J Clin Invest 1992; 89:630–639.

    Article  PubMed  CAS  Google Scholar 

  98. Huang ZQ, Sanders PW. Biochemical interaction between Tamm-Horsfall glycoprotein and Ig light chains in the pathogenesis of cast nephropathy. Lab Invest 1995; 73:810–817.

    PubMed  CAS  Google Scholar 

  99. Stevens FJ, Argon Y. Protein folding in the ER. Semin Cell Dev Biol 1999; 10:443–454.

    Article  PubMed  CAS  Google Scholar 

  100. Hendershot L, Wei J, Gaut J, Melnick J, Aviel S, Argon Y. Inhibition of immunoglobulin folding and secretion by dominant negative BiP ATPase mutants. Proc Natl Acad Sci USA 1996; 93:5269–5274.

    Article  PubMed  CAS  Google Scholar 

  101. Skowronek MH, Hendershot LM, Haas IG. The variable domain of nonassembled Ig light chains determines both their half-life and binding to the chaperone BiP. Proc Natl Acad Sci USA 1998;95:1574–1578.

    Article  PubMed  CAS  Google Scholar 

  102. Davis DP, Khurana R, Meredith S, Stevens FJ, Argon Y. Mapping the major interaction between binding protein and Ig light chains to sites within the variable domain. J Immunol 1999; 163:3842–3850.

    PubMed  CAS  Google Scholar 

  103. Davis PD, Raffen R, Dul JL, et al. Inhibition of amyloid fiber assembly by both BiP and its target peptide. Immunity 2000; 13:433–442.

    Article  PubMed  CAS  Google Scholar 

  104. Zhu L, Herrera GA, Murphy-Ullrich JE, Huang ZQ, Sanders PW. Pathogenesis of glomerulosclerosis in light chain deposition disease. Role for transforming growth factor-(3. Am J Pathol 1995; 147:375–385.

    PubMed  CAS  Google Scholar 

  105. Tagouri YM, Sanders PW, Picken MM, Siegal GP, Kerby JD, Herrera GA. In vitro AL-amyloid formation by rat and human mesangial cells. Lab Invest 1996; 74:290–302.

    PubMed  CAS  Google Scholar 

  106. Isaac J, Kerby JD, Russel WJ, Dempsey SC, Sanders PW, Herrera GA. In vitro modulation of AL-amyloid formation by human mesangial cells exposed to amyloidogenic light chains. Amyloid: Int J Exp Clin Invest 1998; 5:238–246.

    CAS  Google Scholar 

  107. Herrera GA, Russell WJ, Isaac J, et al. Glomerulopathic light chain-mesangial cell interactions modulate in vitro extracellular matrix remodeling and reproduce mesangiopathic effects documented in vivo. Ultrastruct Pathol 1999; 23:107–126.

    Article  PubMed  CAS  Google Scholar 

  108. Zhu L, Herrera GA, White CR, Sanders PW. Immunoglobulin light chain alters mesangial cell calcium homeostasis. Am J Physiol 1997; 272:F319-F324.

    PubMed  CAS  Google Scholar 

  109. Turbat-Herrera EA, Isaac J, Sanders PW, Truong LD, Herrera GA. Integrated expression of glomerular extracellular matrix proteins and beta 1 integrins in monoclonal light chain related renal diseases. Mod Pathol 1997; 10:485–495.

    PubMed  CAS  Google Scholar 

  110. Bruneval P, Foidart JM, Nochy D, Camilleri JP, Bariety J. Glomerular matrix proteins in nodular glomerulosclerosis in association with light chain deposition disease and diabetes mellitus. Hum Pathol 1985; 16:477–484.

    Article  PubMed  CAS  Google Scholar 

  111. Russell WJ, Cardelli J, Harris E, Baier RJ, Herrera GA. Monoclonal light chain-mesangial cell interactions: early signaling events and subsequent pathologic effects Lab Invest 2001; 81:689–703.

    Article  PubMed  CAS  Google Scholar 

  112. Isaac J, Herrera GA. Renal biopsy as a primary diagnostic tool in plasma cell dyscrasias. Pathol Case Rev 1998; 3:183–189.

    Article  Google Scholar 

  113. Abe M, Goto T, Kennel SJ, et al. Production and immunodiagnostic applications of anti-human light chain monoclonal antibodies. Am J Clin Pathol 1993; 100:67–74.

    PubMed  CAS  Google Scholar 

  114. Klastskin G. Non-specific green birefringence in Congo-red stained tissues. Am J Pathol 1969;56:1–13.

    Google Scholar 

  115. Carson FL, Kingsley WB. Non-amyloid green birefringence following Congo red staining. Arch Pathol Lab Med 1980; 104:333–335.

    PubMed  CAS  Google Scholar 

  116. Puchtler H, Waldrop FS, McLoan SN. A review of light, polarization and fluorescence microscopic methods for amyloid. Appl Pathol 1985; 3:5–17.

    PubMed  CAS  Google Scholar 

  117. Arbustini E, Morbini P, Verga L, et al. Light and election microscopy immunohistochemical characterization of amyloid deposits. Amyloid: Int J Exp Clin Med 1997; 4:157–170.

    CAS  Google Scholar 

  118. Pepys MB, Rademacher TW, Amatayakul-Chantler S, et al. Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure. Proc Natl Acad Sci USA 1994; 91:5602–5606.

    Article  PubMed  CAS  Google Scholar 

  119. Rocken C, Schwotzer EB, Linke RP, Saeger W. The classification of amyloid deposits in clinicopathological practice. Histopathology 1996; 29:325–335.

    Article  PubMed  CAS  Google Scholar 

  120. Benson MD. The metabolic and molecular bases of inherited disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. Amyloidosis 8th ed. New York: McGraw Hill, 2001:5345–5378.

    Google Scholar 

  121. Anesi E, Palladini G, Perfetti V, Arbustini E, Obici L, Merlini G. Therapeutic advances demand accurate typing of amyloid deposits. Am J Med 2001; 111:243–244.

    Article  PubMed  CAS  Google Scholar 

  122. Lachmann HJ, Booth DR, Booth SE, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med 2002; 346:1786–1791.

    Article  PubMed  CAS  Google Scholar 

  123. Solomon A, Weiss DT, Macy SD, Antonucci RA. Immunocytochemical detection of kappa and lambda light chain V region subgroups in human B-cell malignancies. Am J Pathol 1990; 137:855–862.

    PubMed  CAS  Google Scholar 

  124. Harrison HH. The “ladder light chain” or “pseudo-oligoclonal” protein in urinary immunofixation electrophoresis (IFE) studies: a distinctive IFE pattern and an explanatory hypothesis relating it to free polyclonal light chains. Clin Chem 1991; 37:1559–1564.

    PubMed  CAS  Google Scholar 

  125. Nakano T, Nagata A. ELISAs for free light chains of human immunoglobulins using monoclonal antibodies: comparison of their specificity with available polyclonal antibodies. J Immunol Methods 2003; 275:9–17.

    Article  PubMed  CAS  Google Scholar 

  126. Bradwell AR, Carr-Smith HD, Mead GP, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 2001; 47:673–680.

    PubMed  CAS  Google Scholar 

  127. Katzmann JA, Clark RJ, Abraham RS, et al. Serum.reference intervals and diagnostic ranges for free K and free A, immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem 2002; 48:1437–1444.

    PubMed  CAS  Google Scholar 

  128. Abraham RS, Clark RJ, Bryant SC, et al. Correlation of serum immunoglobulin free light chain quantification with urinary Bence-Jones protein in light chain myeloma. Clin Chem 2002; 48:655–657.

    PubMed  CAS  Google Scholar 

  129. Le Bricon TL, Bengoufa D, Benlakehal M, Bousquet B, Erlich D. Urinary free light chain analysis by the Freelite(r) immunoassay: a preliminary study in multiple myeloma. Clin Biochem 2002; 35:565–567.

    Article  PubMed  Google Scholar 

  130. Drayson M, Tang LX, Drew R, Mead GP, Carr-Smith H, Bradwell AR. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001; 97:2900–2902.

    Article  PubMed  CAS  Google Scholar 

  131. Abraham RS, Katzmann J A, Clark RJ, Bradwell AR, Kyle RA, Gertz MA. Quantitative analysis of serum free light chains. A new marker for the diagnostic evaluation of primary systemic amyloidosis. Am J Clin Pathol 2003; 119:274–278.

    Article  PubMed  CAS  Google Scholar 

  132. Heilman RL, Velosa JA, Holley KE, Offord KP, Kyle RA. Long-term follow-up and response to chemotherapy in patients with light-chain deposition disease. Am J Kidney Dis 1992; 20:34–41.

    PubMed  CAS  Google Scholar 

  133. Kyle RA, Gertz MA, Greipp PR, et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N Engl J Med 1997; 336:1202–1207.

    Article  PubMed  CAS  Google Scholar 

  134. Zomas A, Dimopoulos MA. Conventional treatment of myeloma. In: Mehta J, Singhal S, eds. Myeloma. London: Martin Dunitz, 2002:313–326.

    Google Scholar 

  135. Dhodapkar MV, Jagannath S, Vesole D, et al. Treatment of AL-amyloidosis with dexam-ethasone plus alpha interferon. Leuk Lymphoma 1997; 27:351–356.

    PubMed  CAS  Google Scholar 

  136. Palladini G, Anesi E, Perfetti V, et al. A modified high-dose dexamethasone regimen for primary systemic (AL) amyloidosis. Br J Haematol 2001; 113:1044–1046.

    Article  PubMed  CAS  Google Scholar 

  137. Singhal S, Mehta J, Desikan R, et al. Anti-tumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341:1565–1571.

    Article  PubMed  CAS  Google Scholar 

  138. Barlogie B, Tricot G, Anaissie E. Thalidomide in the management of multiple myeloma. Semin Oncol 2001; 28:577–582.

    Article  PubMed  CAS  Google Scholar 

  139. Richardson PG, Schlossman RL, Weller E, et al. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 2002; 3063–3067.

    Google Scholar 

  140. Munshi NC, Tricot G, Desikan R, et al. Clinical activity of arsenic trioxide for the treatment of multiple myeloma. Leukemia 2002; 16:1835–1837.

    Article  PubMed  CAS  Google Scholar 

  141. Barlogie B, Shaughnessy J, Zangari M, Tricot G. High-dose therapy and immunomodulatory drug in multiple myeloma. Semin Oncol 2002; 29:26–33.

    PubMed  CAS  Google Scholar 

  142. Kyle RA. High-dose therapy in multiple myeloma and primary amyloidosis: an overview. Semin Oncol 1999; 26:74–83.

    PubMed  CAS  Google Scholar 

  143. Desikan R, Barlogie B, Sawyer J, et al. Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood 2000; 95:4008–4010.

    PubMed  CAS  Google Scholar 

  144. Moreau P, Facon T, Attal M, et al. Comparison of 200 mg/m2 melphalan and 8 Gy total body irradiation plus 140 mg/m2 melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myelome 9502 randomized trial. Blood 2002; 99:731–735.

    Article  PubMed  CAS  Google Scholar 

  145. Singhal S. High-dose therapy and autologous transplantation. In: Mehta J, Singhal S, eds. Myeloma. London: Martin Dunitz, 2002:327–347.

    Google Scholar 

  146. Mehta J. Allogeneic hematopoietic stem cell transplantation in myeloma. In: Mehta J, Singhal S, eds. Myeloma. London: Martin Dunitz, 2002:349–365.

    Google Scholar 

  147. Comenzo RL, Gertz MA. Autologous stem cell transplantation for primary systemic amyloidosis. Blood 2002; 99:4276–4282.

    Article  PubMed  CAS  Google Scholar 

  148. Child J A, Morgan GJ, Davies FE, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348:175–183.

    Article  Google Scholar 

  149. Sezer O, Schmid P, Shweigert M, et al. Rapid reversal of nephrotic syndrome due to primary systemic AL amyloidosis after VAD and subsequent high-dose chemotherapy with autologous stem cell support. Bone Marrow Transplant 1999; 23:967–969.

    Article  PubMed  CAS  Google Scholar 

  150. San Miguel JF, Lahuerta JJ, Garcia-Sanz R, et al. Are myeloma patients with renal failure candidates for autologous stem cell transplantation? Hematol J 2000; 1:28–36.

    Article  PubMed  CAS  Google Scholar 

  151. Badros A, Barlogie B, Siegel E, et al. Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Br J Haematol 2001; 114:822–829.

    Article  PubMed  CAS  Google Scholar 

  152. Sirohi B, Powles R, Mehta J, et al. The implication of compromised renal function at presentation in myeloma: similar outcome in patients who receive high-dose therapy: a single-center study of 251 previously untreated patients. Med Oncol 2001; 18:39–50.

    Article  PubMed  CAS  Google Scholar 

  153. Casserly LF, Fadia A, Sanchorawala V, et al. High-dose intravenous melphalan with autologous stem cell transplantation in AL amyloidosis-associated end-stage renal disease. Kidney Int 2003; 63:1051–1057.

    Article  PubMed  CAS  Google Scholar 

  154. Komatsuda A, Wakui H, Ohtani H, et al. Disappearance of nodular mesangial lesions in a patient with light chain nephropathy after long-term chemotherapy. Am J Kidney Dis 2000; 35:E9.

    Article  PubMed  CAS  Google Scholar 

  155. Hotta O, Taguma Y. Resolution of nodular glomerular lesions in a patient with light-chain nephropathy. Nephron 2002; 91:504–505.

    Article  PubMed  Google Scholar 

  156. Gerlag PG, Koene AK, Berden JH. Renal transplantation in light chain nephropathy: case report and review of the literature. Clin Nephrol 1986; 25:101–104.

    PubMed  CAS  Google Scholar 

  157. Pasternack A, Ahonen J, Kuhlback B. Renal transplantation in 45 patients with amyloidosis. Transplantation 1986; 42:598–601.

    Article  PubMed  CAS  Google Scholar 

  158. Short AK, O’Donoghue DJ, Riad HN, Short CD, Roberts IS. Recurrence of light chain nephropathy in a renal allograft. A case report and review of the literature. Am J Nephrol 2001;21:237–240.

    Article  PubMed  CAS  Google Scholar 

  159. Teoh G, Chen L, Urashima M, et al. Adenovirus vector-based purging of multiple myeloma cells. Blood 1998; 92:4591–4601.

    PubMed  CAS  Google Scholar 

  160. Anderson KC. Multiple myeloma. Advances in disease biology: therapeutic implications. Semin Hematol 2001; 38:6–10.

    Article  PubMed  CAS  Google Scholar 

  161. Border WA, Nobel NA. TGF-beta in kidney fibrosis: a target for gene therapy. Kidney Int 1997;51:1388–1396.

    Article  PubMed  CAS  Google Scholar 

  162. Dul JL, Davis DP, Williamson EK, Stevens FJ, Argon Y. Hsp 70 and antifibrillogenic peptides promote degradation and inhibit intracellular aggregation of amyloidogenic light chains. J Cell Biol 2001; 152:705–716.

    Article  PubMed  CAS  Google Scholar 

  163. Kim Y, Wall JS, Meyer J, et al. Thermodynamic modulation of light chain amyloid fibril formation. J Biol Chem 2000; 275:1570–1574.

    Article  PubMed  CAS  Google Scholar 

  164. Kim YS, Cape SP, Chi E, et al. Counteracting effects of renal solutes on amyloid fibril formation by immunoglobulin light chains. J Biol Chem 2001; 276:1626–1633.

    Article  PubMed  CAS  Google Scholar 

  165. Gianni L, Bellotti V, Gianni AM, Merlini G. New drug therapy of amyloidosis: resorption of AL-type deposits with 4(-iodo-4(-deoxydoxorubicin. Blood 1995; 86:855–861.

    PubMed  CAS  Google Scholar 

  166. Merlini G, Anesi E, Garini P, et al. Treatment of AL amyloidosis with 4’-iodo-4’-deoxydoxorubicin: an update. Blood 1999; 93:1112–1113.

    PubMed  CAS  Google Scholar 

  167. Gertz MA, Lacy MQ, Dispenzieri A, et al. A multicenter phase II trial of 4’-iodo-4’-deoxydoxorubicin (IDOX) in primary amyloidosis (AL) Amyloid: J Protein Folding Disord 2002; 9:24–30.

    Article  CAS  Google Scholar 

  168. Kisilevsky R, Lemieux LJ, Fraser PE, Kong X, Hultin PG, Szarek WA. Arresting amyloidosis in vivo using small-molecule anionic sulphonates or sulphates: implications for Alzheimer’s disease. Nat Med 1995; 1:143–148.

    Article  PubMed  CAS  Google Scholar 

  169. Pepys MP, Herbert J, Hutchinson WL, et al. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature 2002; 417:254–259.

    Article  PubMed  CAS  Google Scholar 

  170. Hrncic R, Wall J, Wolfenbarger DA, et al. Antibody-mediated resolution of light chain-associated amyloid deposits. Am J Pathol 2000; 157:1239–1246.

    Article  PubMed  CAS  Google Scholar 

  171. Solomon A, Weiss DT, Wall JS. Therapeutic potential of chimeric amyloid-reactive monoclonal antibody 11–1F4. Clin Cancer Res 2003; 9:3831S–3838S.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Alan Solomon MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Deborah T. Weiss BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guillermo A. Herrera MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute for Myeloma and Bone Cancer Research, Los Angeles, CA, USA

    James R. Berenson MD

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

Solomon, A., Weiss, D.T., Herrera, G.A. (2004). Renal Diseases Associated With Multiple Myeloma and Related Plasma Cell Dyscrasias. In: Berenson, J.R. (eds) Biology and Management of Multiple Myeloma. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-817-5_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-817-5_14

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-143-1

  • Online ISBN: 978-1-59259-817-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation