Topic Discussion: Myeloma and the kidney- why?

Why do the free light chains affect the kidney? How does the injury happen?
Research in this matter has revealed significant insight.
The three mechanisms are:

1. Direct toxic effects of the free light chains on the proximal tubular cells leading to apoptosis , cytokine generation and cell injury.
2. The light chains have direct inflammatory effects mediated due to excessive endocytosis through the tandem endocytic receptors. This leads to increased inflammatory cytokine production and damage.
3. The free light chains can bind to Tamm-Horsfall protein and lead to myeloma cast formation leading to the intratubular obstructive damage that we clinically observe.

A nice review can be found in ACKD.