Pathophysiology of acute Bence-Jones protein nephrotoxicity in the rat

Weiss, Jay H.; Williams, Robert H.; Galla, John H.; Gottschall, Jerome L.; Rees, E. Douglas; Bhathena, Dinyar; Luke, Robert G.

doi:10.1038/ki.1981.122

Cited by 56 publications

(20 citation statements)

References 26 publications

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“…In the competition study with BJPs, different BJPs replaced each other despite having different isotypes (K or X). Other investigators showed that both K and X BJPs deposited as casts in mouse and rat kidneys (13)(14)(15)(16)(17)(18)(19)29). The difference in the binding affinity in the current study was also not related directly to the isoelectric point of BJPs (Table III).…”

Section: Resultssupporting

confidence: 50%

“…These intraluminal casts are composed of Bence Jones protein (BJP)' and Tamm-Horsfall glycoprotein (THP) (8), a protein that is synthesized by cells of the thick ascending limb of the loop of Henle (9,10) and is the major constituent ofurinary casts ( 11 ). As shown originally by Koss et al ( 12) and confirmed by others (13)(14)(15)(16)(17)(18)(19), cast nephropathy can be reproduced in mice and rats by parenteral injection of purified human Bence Jones protein. We have demonstrated that cast-forming human Bence Jones proteins coaggregate with Tamm-Horsfall glycoprotein to obstruct the distal nephron (14)(15)(16).…”

Section: Introductionmentioning

confidence: 51%

“…We have demonstrated that cast-forming human Bence Jones proteins coaggregate with Tamm-Horsfall glycoprotein to obstruct the distal nephron (14)(15)(16). In addition, intravenous infusion ofnephrotoxic human Bence Jones protein in rats elevates proximal tubule pressure and simultaneously decreases single nephron glomerular filtration rate; intraluminal protein casts were identified in these kidneys (18). Thus, intraluminal obstruction from cast formation appears to be a prominent cause of acute renal failure in multiple myeloma.…”

Section: Introductionmentioning

confidence: 95%

“…This study did not determine that property or peptide sequence responsible for nephrotoxicity, but has provided a means to study further protein nephrotoxicity; defining these nephrotoxic properties is a future direction of this laboratory. The primary cause of cast formation in myeloma kidney is filtered BJP from the blood stream (12)(13)(14)(15)(16)(17)(18)(19). In a previous study, we showed that BJPMiC BJPrap, and BJPdon aggregated with THP in vitro.…”

Section: Biprhymentioning

confidence: 99%

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Bence Jones proteins bind to a common peptide segment of Tamm-Horsfall glycoprotein to promote heterotypic aggregation.

Huang¹,

Kirk²,

Connelly³

et al. 1993

J. Clin. Invest.

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Bence Jones proteins (BJPs) are the major pathogenic factor causing cast nephropathy ("myeloma kidney") by coaggregation with Tamm-Horsfall glycoprotein (THP). Understanding the interaction between these proteins is therefore important in developing treatment strategies to prevent renal failure from cast formation in multiple myeloma. We developed an enzymelinked immunoassay to examine this phenomenon. Five different human BJPs (four K and one X immunoglobulin light chains) were used in this assay that demonstrated these proteins bound THP with different affinity. BJPs competed among themselves for binding to THP. The binding site was a peptide portion of THP since these proteins also bound deglycosylated THP. Also, one monoclonal antibody directed against a peptide segment of human THP prevented binding of THP to BJPs. By altering the conformation of THP, reducing agents decreased binding between these two proteins in concentration-dependent fashion. In turbidity studies, the monoclonal antibody that prevented binding and a reducing agent, dithiothreitol, decreased coaggregation. Deglycosylated THP did not coaggregate with BJPs. We concluded that ionic interaction between BJPs and a specific peptide binding site on THP promoted heterotypic coaggregation. The carbohydrate moiety of THP was also essential for coaggregation, perhaps by facilitating homotypic aggregation of THP. (J. Clin. Invest. 1993. 92:2975-2983

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Section: Resultssupporting

confidence: 50%

Section: Introductionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 95%

Section: Biprhymentioning

confidence: 99%

See 2 more Smart Citations

Bence Jones proteins bind to a common peptide segment of Tamm-Horsfall glycoprotein to promote heterotypic aggregation.

Huang¹,

Kirk²,

Connelly³

et al. 1993

J. Clin. Invest.

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show abstract

“…In a study performed by Weiss et al, intravenous infusion of monoclonal free light chains (FLCs) in rats increases pressure in the proximal tubule and concurrently decreases glomerular filtration rate (GFR); also, rats affected by monoclonal FLCs were identified of having intraluminal casts (36).…”

Section: Light Chain Cast Nephropathymentioning

confidence: 99%