Cast nephropathy is the result of coprecipitation of immunoglobulin free light chains (FLCs) with Tamm-Horsfall glycoprotein (THP). It is a hallmark of multiple myeloma that has significant consequences. Treatment strategies in the past focused on reduction of serum FLC by control of the myeloma. In this issue, Ying et al. report on their successful synthesis of a cyclized competitor peptide that blocks the binding of FLC to THP. In animal studies, this cyclized peptide was capable of reducing cast formation and kidney injury, representing a novel treatment strategy for cast nephropathy that does not depend on the responsiveness of the myeloma to chemotherapy.
Treatment of cast nephropathy by targeting THP and FLC interaction.