IN THE NEWS: Treating Cast Nephropathy without treating the myeloma!

Myeloma kidney is a common complication of multiple myeloma (MM).  There has been data now that supports that free light chains co precipitate with Tamm Horsfall gycoprotein (THP) in the lumen of the distal nephron and leading to intratubular obstruction leading to clinically evident cast nephropathy.  Ying et al show in  this elegant paper in JCI about inhibiting this interaction of free light chains with THP.  There is an area on the free light chains called the complementarity determining region 3(CDR3) that is very important to allow interaction with the THP.  To demonstrate further, the investigators show that when you competitively inhibit that peptide, the free light chains did not bind to the THP in vitro.  Then in a rodent model of cast nephropathy, this inhibitor of CDR3 prevented cast formation and prevented manifestations of the kidney injury in vivo.


This is an interesting study as it doesn't treat the underlying disease which is MM but is attempting to treat in an animal model a consequence of the disease.  Cast nephropathy which leads to intra tubular obstruction can quickly lead to dialysis in many cases.  This is a study that shows by using the CDR3 inhibitor, we prevent this bad light chain and THP combo and prevent the precipitation in the tubules.  We also know that the free light chains behave differently in each MM case. In some cases, we get cast nephrpathy and in some cases we get light chain deposition disease and some amyloidosis.  It appears to be characteristics of the specific light chains produced. While this method might be optimal for cast nephrpathy cases, don't know if this will prevent all MM associated renal diseases.  Regardless, this study might lead to growing MM related cast nephropathy studies with this inhibitor; hopefully.


Ref:
http://www.ncbi.nlm.nih.gov/pubmed/22484815