Go to JCI Insight
Jci spelled out white on transparent.20160208
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews...
    • Cellular senescence in human disease (Apr 2018)
    • Fibrosis (Jan 2018)
    • Glia and Neurodegeneration (Sep 2017)
    • Transplantation (Jun 2017)
    • Nuclear Receptors (Apr 2017)
    • Metabolism and Inflammation (Jan 2017)
    • Hypoxia and Inflammation (Oct 2016)
    • View all review series...
  • Collections
    • Recently published
    • Commentaries
    • Concise Communication
    • Editorials
    • Opinion
    • Scientific Show Stoppers
    • Top read articles
    • In-Press Preview
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

Jci only white

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Current issue
  • Past issues
  • By specialty
  • Subscribe
  • Alerts
  • Advertise
  • Contact
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • Brief Reports
  • Technical Advances
  • Commentaries
  • Editorials
  • Hindsight
  • Review series
  • Reviews
  • The Attending Physician
  • First Author Perspectives
  • Scientific Show Stoppers
  • Top read articles
  • Concise Communication
Mechanism and prevention of acute kidney injury from cast nephropathy in a rodent model
Wei-Zhong Ying, … , Kristal J. Aaron, Paul W. Sanders
Wei-Zhong Ying, … , Kristal J. Aaron, Paul W. Sanders
Published May 1, 2012
Citation Information: J Clin Invest. 2012;122(5):1777-1785. https://doi.org/10.1172/JCI46490.
View: Text | PDF
Categories: Research Article Nephrology

Mechanism and prevention of acute kidney injury from cast nephropathy in a rodent model

  • Text
  • PDF
Abstract

A common renal complication of multiple myeloma is “myeloma kidney,” a condition also known as cast nephropathy. The renal lesions (casts) are directly related to the production of monoclonal immunoglobulin free light chains (FLCs), which coprecipitate with Tamm-Horsfall glycoprotein (THP) in the lumen of the distal nephron, obstructing tubular fluid flow. Here, we report that analysis of the binding interaction between FLCs and THP demonstrates that the secondary structure and key amino acid residues on the complementarity-determining region 3 (CDR3) of FLCs are critically important determinants of the molecular interaction with THP. The findings permitted development of a cyclized competitor peptide that demonstrated strong inhibitory capability in the binding of FLCs to THP in vitro. When used in a rodent model of cast nephropathy, this cyclized peptide construct served as an effective inhibitor of intraluminal cast formation and prevented the functional manifestations of acute kidney injury in vivo. These experiments provide proof of concept that intraluminal cast formation is integrally involved in the pathogenesis of acute kidney injury from cast nephropathy. Further, the data support a clinically relevant approach to the management of renal failure in the setting of multiple myeloma.

Authors

Wei-Zhong Ying, Christopher E. Allen, Lisa M. Curtis, Kristal J. Aaron, Paul W. Sanders

×

Figure 2

Mutational analysis of the CDR3 sequence demonstrated the importance of the primary sequence, in particular the fourth amino acid residue, of the CDR3 in binding to THP.

Options: View larger image (or click on image) Download as PowerPoint
Mutational analysis of the CDR3 sequence demonstrated the importance of ...
*P < 0.05, compared with no insert. n = 7 experiments in each group. Data are shown as mean ± SEM.
Follow JCI: Facebook logo white Twitter logo v2 Rss icon
Copyright © 2018 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts