Skip to main content
SpringerLink
Log in

Pathophysiology of myeloma kidney

  • Chapter
Monoclonal Gammopathies and the Kidney

  • 115 Accesses

Abstract

Renal failure occurs commonly in the setting of multiple myeloma, with nearly half of these patients presenting with renal failure or developing this complication over time1,2. The underlying etiology of renal failure is cast nephropathy in nearly two-thirds, with the remainder related largely to AL-type amyloidosis and monoclonal light chain deposition disease3. Of important clinical relevance is that cast nephropathy, or myeloma kidney, represents a potentially reversible form of renal failure. The immunoglobulin light chain takes the ‘center stage’ in discussions of the pathophysiology of cast nephropathy and other renal lesions that develop in multiple myeloma.

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. Kyle RA. Multiple myeloma: review of 869 cases. Mayo Clin Proc. 1975;50:29–40.

    PubMed  CAS  Google Scholar 

  2. Alexanian R, Barlogie B, Dixon D. Renal failure in multiple myeloma. Pathogenesis and prognostic implications. Arch Intern Med. 1990;150:1693–5.

    Article  PubMed  CAS  Google Scholar 

  3. Iványi B. Frequency of light chain deposition nephropathy relative to renal amyloidosis and Bence Jones cast nephropathy in a necropsy study of patients with myeloma. Arch Pathol Lab Med. 1990;114:986–7.

    PubMed  Google Scholar 

  4. Bruccoleri RE, Haber E, Novotny J. Structure of antibody hypervariable loops reproduced by a conformational search algorithm. Nature (Lond). 1988;335:564–8.

    Article  CAS  Google Scholar 

  5. Chothia C, Lesk AM. Canonical structures for the hypervariable regions of immunoglobulins. J Mol Biol. 1987;196:901–17.

    Article  PubMed  CAS  Google Scholar 

  6. Chothia C, Lesk AM, Tramontano A et al. Conformations of immunoglobulin hypervariable regions. Nature (Lond). 1989;342:877–83.

    Article  CAS  Google Scholar 

  7. Glockshuber R, Steipe B, Huber R, Plückthun A. Crystallization and preliminary x-ray studies of the VL domain of the antibody McPC603 produced in Escherichia coli. J Mol Biol. 1990; 213:613–15.

    Article  PubMed  CAS  Google Scholar 

  8. Rocca A, Khamlichi AA, Aucouturier P et al. Primary structure of a variable region of the VKI subgroup (ISE) in light chain deposition disease. Clin Exp Immunol. 1993;91:506–9.

    Article  PubMed  CAS  Google Scholar 

  9. Solomon A. Light chains of immunoglobulins: structural—genetic correlates. Blood. 1986; 68:603–10.

    PubMed  CAS  Google Scholar 

  10. Kabat EA, Wu TT, Bilofsky H. Unusual distributions of amino acids in complementaritydetermining (hypervariable) segments of heavy and light chains of immunoglobulins and their possible roles in specifiicity of antibody-combining sites. J Biol Chem. 1977;252:6606–16.

    Google Scholar 

  11. Ying W-Z, Sanders PW. Mapping the binding domain of immunoglobulin light chains for Tamm—Horsfall protein. Am J Pathol. 2001;158:1859–66.

    Article  PubMed  CAS  Google Scholar 

  12. Pesce AJ, Clyne DH, Pollak VE, Kant SK, Foulkes EC, Selenke WM. Renal tubular interactions of proteins. Clin Biochem. 1980;13:209–15.

    Article  PubMed  CAS  Google Scholar 

  13. Baylis C, Falconer-Smith J, Ross B. Glomerular and tubular handling of differently charged human immunoglobulin light chains by the rat kidney. Clin Sci. 1988;74:639–44.

    PubMed  CAS  Google Scholar 

  14. Smolens P, Miller V. Renal tubular uptake of light chains (LC) of different isoelectric points (pI). Clin Res. 1987;35:33A(abstract).

    Google Scholar 

  15. Batuman V, Dreisbach AW, Cyran J. Light-chain binding sites on renal brush-border membranes. Am J Physiol 258 (Renal Fluid Electrolyte Physiol. 27). 1990;F1259–65.

    Google Scholar 

  16. Batuman V, Guan S. Receptor mediated endocytosis of Bence-Jones proteins by proximal tubule cells. Am J Physiol 272 (Renal Physiol. 41). 1997;F521–30.

    Google Scholar 

  17. Batuman V, Verroust PJ, Navar GL et al. Myeloma light chains are ligands for cubilin (gp280). Am J Physiol 275 (Renal Physiol. 44). 1998;F246–54.

    Google Scholar 

  18. Maack T, Johnson V, Kau ST, Figueiredo J, Sigulem D. Renal fi]iltration, transport, and metabolism of low-molecular-weight proteins: a review. Kidney Int. 1979;16:251–70.

    Article  PubMed  CAS  Google Scholar 

  19. 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: 527–37.

    PubMed  CAS  Google Scholar 

  20. Woodruff R, Sweet B. Multiple myeloma with massive Bence Jones proteinuria and preservation of renal function. Aust NZ J Med. 1977;7:60–2.

    Article  CAS  Google Scholar 

  21. Solomon A, Weiss DT, Kattine AA. Nephrotoxic potential of Bence Jones proteins. N Engl J Med. 1991; 324:1845–51.

    Article  PubMed  CAS  Google Scholar 

  22. Solomon A, Frangione B, Franklin EC. Bence Jones proteins and light chains of immunoglobulins: preferential association of the VλvI subgroup of human light chains with amyloidosis AL(λ). J Clin Invest. 1982;70:453–60.

    Article  PubMed  CAS  Google Scholar 

  23. Cogné M, Preud’homme J-L, Bauwens M, Touchard G, Aucouturier P. Structure of a monoclonal kappa chain of the VKIv subgroup in the kidney and plasma cells in light chain deposition disease. J Clin Invest. 1991;87:2186–90.

    Article  PubMed  Google Scholar 

  24. Preud’homme J-L, Aucouturier P, Touchard G et al. Monoclonal immunoglobulin deposition disease (Randall type). Relationship with structural abnormalities of immunoglobulin chains. Kidney Int. 1994;46:965–72.

    Article  PubMed  Google Scholar 

  25. Zhu L, Herrera GA, Murphy-Ullrich JE, Huang Z-Q, Sanders PW. Pathogenesis of glomerulosclerosis in light chain deposition disease: role for transforming growth factor-β3. Am J Pathol. 1995;147:375–85.

    PubMed  CAS  Google Scholar 

  26. Zhu L, Herrera GA, White CR, Sanders PW. Immunoglobulin light chain alters mesangial cell calcium homeostasis. Am J Physiol 272 (Renal Physiol. 41). 1997;F319–24.

    Google Scholar 

  27. 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 

  28. Isaac J, Kerby JD, Russell WJ, Dempsey SC, Sanders PW, Herrera GA. In vitro modulation of AL-amyloid formation by human mesangial cells exposed to amyloidogenic light chains. Amyloid. 1998;5: 238–46.

    Article  PubMed  CAS  Google Scholar 

  29. Herrera GA, Shultz JJ, Soong S-j, Sanders PW. Growth factors in monoclonal light chain-related renal diseases. Hum Pathol. 1994;25:883–92.

    Article  PubMed  CAS  Google Scholar 

  30. Herrera GA, Russell WJ, Issac J et al. Glomerulopathic light chain-mesangial cell interactions modulate in vitro extracellular matrix remodeling and reproduce mesangiopathic fiindings documented in vivo. Ultrastruct Pathol. 1999;23:107–26.

    Article  PubMed  CAS  Google Scholar 

  31. Sanders PW, Herrera GA, Chen A, Booker BB, Galla JH. Differential nephrotoxicity of low molecular weight proteins including Bence Jones proteins in the perfused rat nephron in vivo. J Clin Invest. 1988;82:2086–96.

    Article  PubMed  CAS  Google Scholar 

  32. Sanders PW, Booker BB, Bishop JB, Cheung HC. Mechanisms of intranephronal proteinaceous cast formation by low molecular weight proteins. J Clin Invest. 1990;85:570–6.

    Article  PubMed  CAS  Google Scholar 

  33. Sanders PW, Booker BB. Pathobiology of cast nephropathy from human Bence Jones proteins. J Clin Invest. 1992;89:630–9.

    Article  PubMed  CAS  Google Scholar 

  34. Huang Z-Q, Kirk KA, Connelly KG, Sanders PW. Bence Jones proteins bind to a common peptide segment of Tamm-Horsfall glycoprotein to promote heterotypic aggregation. J Clin Invest. 1993;92:2975–83.

    Article  PubMed  CAS  Google Scholar 

  35. Huang Z-Q, Sanders PW. Biochemical interaction of Tamm-Horsfall glycoprotein with Ig light chains. Lab Invest. 1995;73:810–17.

    PubMed  CAS  Google Scholar 

  36. Huang Z-Q, Sanders PW. Localization of a single binding site for immunoglobulin light chains on human Tamm–Horsfall glycoprotein. J Clin Invest. 1997;99:732–36.

    Article  PubMed  CAS  Google Scholar 

  37. Sanders PW, Herrera GA, Galla JH. Human Bence Jones protein toxicity in rat proximal tubule epithelium in vivo. Kidney Int. 1987;32:851–61.

    Article  PubMed  CAS  Google Scholar 

  38. Sanders PW, Herrera GA, Lott RL, Galla JH. Morphologic alterations of the proximal tubules in light chain-related renal disease. Kidney Int. 1988;33:881–9.

    Article  PubMed  CAS  Google Scholar 

  39. Weiss JH, Williams RH, Galla JH et al. Pathophysiology of acute Bence-Jones protein nephrotoxicity in the rat. Kidney Int. 1981;20:198–210.

    Article  PubMed  CAS  Google Scholar 

  40. Hoyer JR, Seiler MW. Pathophysiology of Tamm—Horsfall protein. Kidney Int. 1979;16:279–89.

    Article  PubMed  CAS  Google Scholar 

  41. Kumar S, Muchmore A. Tamm—Horsfall protein — uromodulin (1950–1990). Kidney Int. 1990; 37:1395–401.

    Article  PubMed  CAS  Google Scholar 

  42. Rindler MJ, Naik SS, Li N, Hoops TC, Peraldi M-N. Uromodulin (Tamm—Horsfall glycoprotein/ uromucoid) is a phosphatidylinositol-linked membrane protein. J Biol Chem. 1990;265: 20784–9.

    PubMed  CAS  Google Scholar 

  43. Cross GAM. Glycolipid anchoring of plasma membrane proteins. Annu Rev Cell Biol. 1990; 6:1–39.

    Article  PubMed  CAS  Google Scholar 

  44. Scallon BJ, Fung W-JC, Tsang TC et al. Primary structure and functional activity of a phosphatidylinositol-glycan-specific phospholipase D. Science (Wash). 1991;252:446–8.

    Article  CAS  Google Scholar 

  45. Start DA, Silva FG, Davis LD, D’Agati V, Pirani CL. Myeloma cast nephropathy: immunohistochemical and lectin studies. Mod Pathol. 1988;1:336–47.

    PubMed  CAS  Google Scholar 

  46. Winearls CG. Acute myeloma kidney. Kidney Int. 1995;48:1347–61.

    Article  PubMed  CAS  Google Scholar 

  47. Fields S, Song O. A novel genetic system to detect protein—protein interactions. Nature. 1989; 340:245–6.

    Article  PubMed  CAS  Google Scholar 

  48. Zucchelli P, Pasquali S, Cagnoli L, Ferrari G. Controlled plasma exchange trial in acute renal failure due to multiple myeloma. Kidney Int. 1988;33:1175–80.

    Article  PubMed  CAS  Google Scholar 

  49. Ganeval D, Rabian C, Guérin V, Pertuiset N, Landais P, Jungers P. Treatment of multiple myeloma with renal involvement. Adv Nephrol. 1992;21:347–70.

    CAS  Google Scholar 

  50. Ying W-Z, Sanders PW. Expression of Tamm—Horsfall glycoprotein is regulated by dietary salt in rats. Kidney Int. 1998;54:1150–6.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nephrology Research and Training Center, Comprehensive Cancer Center; Cell Adhesion and Matrix Research Center, Division of Nephrology, Department of Medicine and Department of Physiology & Biophysics, University of Alabama at Birmingham, Birmingham, AL, 35294-0007, USA

    P. W. Sanders

  2. Department of Veterans Affairs Medical Center, Birmingham, AL, 35233, USA

    P. W. Sanders

Authors
  1. P. W. Sanders
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University Hospital, Poitiers, France

    Guy Touchard

  2. Tenon Hospital, Paris, France

    Pierre Aucouturier  & Pierre Ronco  & 

  3. Necker Hospital, Paris, France

    Olivier Hermine

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Sanders, P.W. (2003). Pathophysiology of myeloma kidney. In: Touchard, G., Aucouturier, P., Hermine, O., Ronco, P. (eds) Monoclonal Gammopathies and the Kidney. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-0191-4_5

Download citation

  • DOI: https://doi.org/10.1007/978-94-017-0191-4_5

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-6199-7

  • Online ISBN: 978-94-017-0191-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation