Researchers at the University of Alabama at Birmingham have discovered a way to prevent kidney failure from occurring in people with multiple myeloma.
Paul Sanders, M.D., a nephrologist in the Division of Nephrology at UAB, found that the development of chronic, progressive kidney damage can be prevented by blocking a pathway activated in the kidney by light chains proteins produced by cancer cells.
“In the process of catabolism by the kidney, certain monoclonal Ig light chains, FLCs, can promote significant changes in kidney epithelial cell biology,” Sanders said. “In this paper, we demonstrated that monoclonal FLCs are biologically active proteins that can generate hydrogen peroxide in amounts sufficient to activate intracellular redox-sensitive signaling pathways in the proximal tubule. We further identified a novel intracellular signal transduction mechanism that generated a pro-inflammatory and pro-fibrotic milieu in the kidney and featured Signal Transducer and Activator of Transcription 1, so-called STAT1. To the extent that the experiments reflect the human condition, the studies offered new insights into the pathogenesis of progressive kidney failure that develops in the setting of multiple myeloma, which features increased circulating levels of monoclonal immunoglobulin fragments that require metabolism by the kidney.”