Monoclonal glomerulopathy with features of cryoglobulinemic glomerulopathy in murine multiple myeloma model

Ultrastruct Pathol. 2020 Nov 20;44(4-6):387-394. doi: 10.1080/01913123.2020.1841349. Epub 2020 Nov 1.

Abstract

In vivo and animal models of monoclonal light chain-associated renal diseases are limited. The Vk*MYC transgenic model with multiple myeloma in 50-70 weeks old mice with renal involvement has been reported before, but detailed renal pathologic changes have not been well documented. This study fully investigated pathologic changes in the kidneys of Vk*MYC transgenic model using light microscopy, immunofluorescence stains for kappa and lambda light chains, and electron microscopy. Compared to the kidneys of wild-type mice, the kidneys of transgenic mice showed either mesangial segmental expansion, some with associated hypercellularity, and/or thrombotic obstruction of glomerular capillaries. The glomeruli revealed stronger lambda staining than kappa light chain staining. Six out of 12 kidneys from transgenic mice showed abundant electron-dense deposits when examined ultrastructurally. The deposits were located in glomerular capillary lumina in three cases. Large luminal and subendothelial deposits were characterized by randomly disposed microtubular structures measuring up to 16 nm in diameter, with overall features most consistent with cryoglobulins. In summary, about 50% of kidneys from the Vk*MYC mice with myeloma had features most consistent with monoclonal cryoglobulinemic glomerulopathy.

Keywords: Monoclonal gammopathy; cyoglobulinemic glomerulopathy; transgenic model of myeloma.

MeSH terms

  • Animals
  • Cryoglobulinemia / etiology
  • Cryoglobulinemia / pathology*
  • Disease Models, Animal
  • Immunoglobulin Light Chains
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / ultrastructure*
  • Mice
  • Mice, Transgenic
  • Multiple Myeloma / complications
  • Multiple Myeloma / pathology*
  • Multiple Myeloma / ultrastructure*

Substances

  • Immunoglobulin Light Chains