In this issue of Leukemia and Lymphoma, Minarik and colleagues report three patients with renal biopsy-proven light chain deposition disease [1]. All three were treated with bortezomib and achieved hematologic responses with normalization of the free light ratio in all, a 50% reduction in proteinuria in all, and 50% reduction in creatinine in two of the three. Significant neurotoxicity was seen requiring discontinuation of bortezomib in two. The renal manifestations associated with monoclonal immunoglobulin light chains are many. The most common occurs when an immunoglobulin light chain binds to a common site on Tamm-Horsfall protein, a glycoprotein secreted by the thick ascending limb of Henle loop. Aggregation of these protein complexes produces casts that obstruct tubule fluid flow resulting in renal failure, so-called myeloma cast nephropathy [2].

IgM monoclonal proteins can bind to polyclonal IgG immunoglobulin resulting in immune complexes that can deposit in the kidney leading to proteinuria and an active urinary sediment. When immune complexes precipitate in the cold they are type II cryoglobulins. Occasionally, monoclonal immunoglobulin K chains can form crystalline deposits in the proximal renal tubule leading to the disruption of transport of glucose, uric acid, phosphorus and amino acids. The characteristic laboratory finding is amino aciduria and the complex is referred to as Fanconi syndrome. The loss of phosphorus in the urine and the resulting rise in parathyroid hormone leads to vitamin D-resistant rickets. Microscopic bone fractures are the presenting clinical manifestation [3]. There are two renal disorders associated with monoclonal immunoglobulin light chains that result from protein misfolding. One is light chain amyloidosis where fragments of immunoglobulin light chain, usually λ or heavy chain, misfold into a β-pleated sheet configuration. These misfolded light chains are insoluble and deposit as fibrils in any tissue, with the kidney being the most frequently affected. The clinical manifestation is nephrotic range proteinuria. The other form of monoclonal immunoglobulin light chain deposition is usually associated with K light chains. This syndrome was first described by Randall [4] and is referred to as light chain deposition disease, Randall type, in order to distinguish light