Light chain-mediated tubulopathies

Contrib Nephrol. 2011:169:262-269. doi: 10.1159/000313959. Epub 2011 Jan 20.

Abstract

Immunoglobulin light chains are low molecular weight proteins that are filtered through the glomerulus and reabsorbed into the proximal tubular epithelium by binding initially to a heteromeric receptor complex composed of megalin and cubilin. Saturation of this receptor-mediated endocytotic process results in the presence of free light chains in the distal nephron and urine. In the course of metabolism of monoclonal light chains, nephrotoxicity can occur, resulting in clinical manifestations that can include acute kidney injury and progressive chronic kidney disease. Patterns of tubulopathic renal injury include proximal tubular epithelial cell cytotoxicity, tubulointerstitial nephritis and cast nephropathy (also known as 'myeloma kidney'). Research efforts over the past two decades have refined understanding of the molecular mechanisms involved in light chain-mediated tubular injury and are the subject of this review.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Endocytosis / physiology
  • Humans
  • Immunoglobulin Light Chains / physiology*
  • Kidney Diseases / immunology*
  • Kidney Diseases / physiopathology*
  • Kidney Tubules, Proximal / immunology
  • Kidney Tubules, Proximal / physiopathology
  • Low Density Lipoprotein Receptor-Related Protein-2 / physiology
  • Nephritis, Interstitial / immunology
  • Nephritis, Interstitial / physiopathology
  • Receptors, Cell Surface / physiology

Substances

  • Immunoglobulin Light Chains
  • Low Density Lipoprotein Receptor-Related Protein-2
  • Receptors, Cell Surface
  • intrinsic factor-cobalamin receptor