Abstract: FR-PO699

Pathologic Findings in Monoclonal Glomerulopathy with Features of Cryoglobulinemic Nephropathy in the Kidneys of a Vk*MYC Transgenic Model of Multiple Myeloma

Session Information

Category: Glomerular

  • 1002 Glomerular: Basic/Experimental Pathology

Authors

  • Zhang, Ping L., Beaumont Health System, Royal Oak, Michigan, United States
  • Herrera, Guillermo A., Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States
  • Lewinski, Karen L, Beaumont Health System, Royal Oak, Michigan, United States
  • Liu, Bei, Medical University of South Carolina, Charleston, South Carolina, United States
Background

There are only a few animal models of monoclonal light chain-associated renal diseases and no animal models of monoclonal cryoglobulinemic nephropathy (CN) that can be used to evaluate treatment modalities. The Vk*MYC transgenic model in 50-70 weeks old mice with renal involvement has been reported before (Chesi et al., 2008) but detailed renal pathologic changes have not been well documented. This study fully investigates pathologic changes in these kidneys.

Methods

The kidneys of 6 wild type and 12 Vk*MYC transgenic mice were investigated using routine light microscopy (LM), immunofluorescence stains for light chains (IF), and electron microscopy (EM). The EM score system developed to evaluate findings is as follows: 0 – no deposits, +/- minimal electron dense deposits, 1+ - mild deposits, 2+ - moderate deposits and 3+ - moderate to prominent deposits with subendothelial deposits.

Results

By LM, wild-type kidneys were unremarkable. However, the kidneys from transgenic mice showed either mesangial segmental expansion, some with associated hypercellularity and /or thrombotic obstruction of glomerular capillaries. By IF, the glomeruli of wild-type mice showed minimal or no staining for both kappa and lambda. In the transgenic mice, lambda was 2+, stronger than kappa 1+ staining in glomeruli as a reversed pattern in 3 mice. In the aging wild-type mice, minimal electron dense deposits can be seen in the mesangial areas by EM. Notably, in transgenic mice, 6 out of 12 kidneys showed mild mesangial deposits (1+). The other 6 kidneys from the transgenic mice showed 2-3+ electron dense deposits. The deposits were located in glomerular capillary lumina in 3 cases. Large luminal and subendothelial deposits were characterized by randomly disposed microtubular structures measuring up to 16 nm in diameter, with overall features consistent with findings CN. Segmental fusion of foot processes were seen, but no mesangial interposition was noted.

Conclusion

Our pathology evaluation suggests that 50% (6/12) of kidneys from the Vk*MYC model of MM had significant EM deposits with features of CN in 3 of them (most likely lambda dominant). This transgenic model of monoclonal-associated glomerulopathy may be useful to evaluate treatment of neoplastic B cell clones with renal manifestations.

Funding

  • Other NIH Support