Abstract: FR-PO680

Visualization of Myeloma Light Chain Filtration and Proximal Tubule Trafficking: Implication for MGUS

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Dean, Dawson, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Sandoval, Ruben M., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Wagner, Mark C., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Campos-bilderback, Silvia B., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Molitoris, Bruce A., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Myeloma light chains are thought to cause acute and chronic kidney injury by several mechanisms including tubular obstruction and direct proximal tubule (PT) injury. Earlier forms of this disease, including Monoclonal Gammopathy of Undetermined Significance (MGUS), are detected by serum markers but their impact on the nephron is not fully understood.

Methods

To study directly the fate of serum myeloma light chains we isolated myeloma light chains from patient urines using gel sizing techniques, conjugated them to Texas Red, and injected either in a pulse chase or pulse with a continuous infusion.

Results

Using 2-photon microscopy of surface glomeruli of Munich Wistar Fromter rats, the glomerular sieving coefficients of these conjugated Myeloma proteins were determined to be 0.14 ± 0.02. Additionally, light chains attached to PT apical membranes within 20 seconds following IV injection, accumulated rapidly in a linear fashion within the apical aspect of the cell and subsequently trafficked to lysosomes. No transcytosis was visualized. Both S1 and S2 segments of PT participated equally in a saturable process with non-reabsorbed light chains being concentrated in distal tubule lumens. These data indicate myeloma light chains are readily filtered across the glomerulus, reabsorbed effectively by PT cells and do not appear in the urine until saturation of PT reabsorption has occurred.

Conclusion

This has important implications in MGUS where PT protein overload and subclinical injury could be occurring without serum or urine evidence of paraproteinemia.

Funding

  • NIDDK Support