• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Feb 1992; 89(2): 630–639.
PMCID: PMC442896

Pathobiology of cast nephropathy from human Bence Jones proteins.


Renal failure is a common accompaniment of multiple myeloma and is usually due to cast nephropathy, or "myeloma kidney." To understand this lesion, four human Bence Jones proteins (BJP) were purified from the urine of volunteers who had either no evidence of renal dysfunction (BJP1) or renal failure from cast nephropathy (BJP2, BJP3, BJP4). When infused directly into the rat nephron in vivo, BJP2, BJP3, and BJP4 produced intraluminal obstruction by precipitating in the distal nephron; protein casts were never identified before the tip of the loop of Henle. Obstruction was related to the concentration of BJP in the perfusate. Addition of furosemide to the perfusate augmented obstruction in a concentration-dependent fashion. Pretreatment of rats with colchicine completely prevented obstruction and cast formation of perfused nephrons; beta-lumicolchicine did not prevent obstruction. Tamm-Horsfall glycoprotein purified from beta-lumicolchicine-treated and untreated rats coaggregated with BJP3 in vitro. Tamm-Horsfall glycoprotein from colchicine-treated rats did not contain sialic acid and did not aggregate with BJP3 in vitro. Thus, cast-forming human BJP coaggregated with Tamm-Horsfall glycoprotein and obstructed the rat distal nephron. Intranephronal obstruction was aggravated by decreasing extracellular fluid volume or adding furosemide. Finally, by decreasing secretion and altering the carbohydrate moiety of Tamm-Horsfall glycoprotein, colchicine prevented intraluminal cast formation and obstruction of the rat nephron.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • EDELMAN GM, GALLY JA. The nature of Bence-Jones proteins. Chemical similarities to polypetide chains of myeloma globulins and normal gamma-globulins. J Exp Med. 1962 Aug 1;116:207–227. [PMC free article] [PubMed]
  • Solomon A. Bence-Jones proteins and light chains of immunoglobulins (first of two parts). N Engl J Med. 1976 Jan 1;294(1):17–23. [PubMed]
  • Solomon A, Weiss DT, Kattine AA. Nephrotoxic potential of Bence Jones proteins. N Engl J Med. 1991 Jun 27;324(26):1845–1851. [PubMed]
  • 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 Apr;64(4):527–537. [PubMed]
  • Weiss JH, Williams RH, Galla JH, Gottschall JL, Rees ED, Bhathena D, Luke RG. Pathophysiology of acute Bence-Jones protein nephrotoxicity in the rat. Kidney Int. 1981 Aug;20(2):198–210. [PubMed]
  • Smolens P, Venkatachalam M, Stein JH. Myeloma kidney cast nephropathy in a rat model of multiple myeloma. Kidney Int. 1983 Aug;24(2):192–204. [PubMed]
  • Sanders PW, Herrera GA, Galla JH. Human Bence Jones protein toxicity in rat proximal tubule epithelium in vivo. Kidney Int. 1987 Dec;32(6):851–861. [PubMed]
  • Sanders PW, Herrera GA, Lott RL, Galla JH. Morphologic alterations of the proximal tubules in light chain-related renal disease. Kidney Int. 1988 Apr;33(4):881–889. [PubMed]
  • 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 Dec;82(6):2086–2096. [PMC free article] [PubMed]
  • Sanders PW, Booker BB, Bishop JB, Cheung HC. Mechanisms of intranephronal proteinaceous cast formation by low molecular weight proteins. J Clin Invest. 1990 Feb;85(2):570–576. [PMC free article] [PubMed]
  • Hoyer JR, Seiler MW. Pathophysiology of Tamm-Horsfall protein. Kidney Int. 1979 Sep;16(3):279–289. [PubMed]
  • Kumar S, Muchmore A. Tamm-Horsfall protein--uromodulin (1950-1990). Kidney Int. 1990 Jun;37(6):1395–1401. [PubMed]
  • TAMM I, HORSFALL FL., Jr Characterization and separation of an inhibitor of viral hemagglutination present in urine. Proc Soc Exp Biol Med. 1950 May;74(1):106–108. [PubMed]
  • Burg M, Stoner L, Cardinal J, Green N. Furosemide effect on isolated perfused tubules. Am J Physiol. 1973 Jul;225(1):119–124. [PubMed]
  • Kirchner KA. Indomethacin antagonizes furosemide's intratubular effects during loop segment microperfusion. J Pharmacol Exp Ther. 1987 Dec;243(3):881–886. [PubMed]
  • Kirchner KA, Voelker JR, Brater DC. Intratubular albumin blunts the response to furosemide-A mechanism for diuretic resistance in the nephrotic syndrome. J Pharmacol Exp Ther. 1990 Mar;252(3):1097–1101. [PubMed]
  • Epstein WV, Gulyassy PF, Tan M, Rae AI. Effect of renal hemotransplantation on the metabolism of the light chains of immunoglobulins. Ann Intern Med. 1968 Jan;68(1):48–62. [PubMed]
  • SOLOMON A, FAHEY JL. BENCE JONES PROTEINEMIA. Am J Med. 1964 Aug;37:206–222. [PubMed]
  • Bachmann S, Metzger R, Bunnemann B. Tamm-Horsfall protein-mRNA synthesis is localized to the thick ascending limb of Henle's loop in rat kidney. Histochemistry. 1990;94(5):517–523. [PubMed]
  • McQueen EG. The nature of urinary casts. J Clin Pathol. 1962 Jul;15(4):367–373. [PMC free article] [PubMed]
  • Cohen AH, Border WA. Myeloma kidney. An immunomorphogenetic study of renal biopsies. Lab Invest. 1980 Feb;42(2):248–256. [PubMed]
  • Dulawa J, Rambausek M, Jann K, Notohamiprodjo M, Ritz E. Abnormal radiofurosemide binding by Tamm Horsfall glycoprotein of diabetic patients. Diabetologia. 1985 Nov;28(11):827–830. [PubMed]
  • Brunisholz MC, Lynn KL, Hunt JS. Loop-acting diuretics do not bind to Tamm-Horsfall urinary glycoprotein. Clin Sci (Lond) 1987 Sep;73(3):305–310. [PubMed]
  • Gutmann EJ, Niles JL, McCluskey RT, Brown D. Colchicine-induced redistribution of an apical membrane glycoprotein (gp330) in proximal tubules. Am J Physiol. 1989 Aug;257(2 Pt 1):C397–C407. [PubMed]
  • Valberg PA, Brain JD, Kane D. Effects of colchicine or cytochalasin B on pulmonary macrophage endocytosis in vivo. J Appl Physiol Respir Environ Exerc Physiol. 1981 Mar;50(3):621–629. [PubMed]
  • Piasek A, Thyberg J. Effects of colchicine on endocytosis of horseradish peroxidase by rat peritoneal macrophages. J Cell Sci. 1980 Oct;45:59–71. [PubMed]
  • Parczyk K, Haase W, Kondor-Koch C. Microtubules are involved in the secretion of proteins at the apical cell surface of the polarized epithelial cell, Madin-Darby canine kidney. J Biol Chem. 1989 Oct 5;264(28):16837–16846. [PubMed]
  • Woodruff R, Sweet B. Multiple myeloma with massive Bence Jones proteinuria and preservation of renal function. Aust N Z J Med. 1977 Feb;7(1):60–62. [PubMed]
  • Clyne DH, Pesce AJ, Thompson RE. Nephrotoxicity of Bence Jones proteins in the rat: importance of protein isoelectric point. Kidney Int. 1979 Sep;16(3):345–352. [PubMed]
  • Tanner GA, Evan AP. Glomerular and proximal tubular morphology after single nephron obstruction. Kidney Int. 1989 Dec;36(6):1050–1060. [PubMed]
  • Bernstein SP, Humes HD. Reversible renal insufficiency in multiple myeloma. Arch Intern Med. 1982 Nov;142(12):2083–2086. [PubMed]
  • Kyle RA. Multiple myeloma: review of 869 cases. Mayo Clin Proc. 1975 Jan;50(1):29–40. [PubMed]
  • Bryan CW, McIntire KR. Effect of sustained diuresis on the renal lesions of mice with Bence Jones protein-producing tumors. J Lab Clin Med. 1974 Mar;83(3):409–416. [PubMed]
  • Holland MD, Galla JH, Sanders PW, Luke RG. Effect of urinary pH and diatrizoate on Bence Jones protein nephrotoxicity in the rat. Kidney Int. 1985 Jan;27(1):46–50. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...