Monoclonal immunoglobulin crystalline nephropathies

Monoclonal immunoglobulin (MIg) crystalline nephropathies are rare lesions resulting from precipitation of MIgs in the kidney as crystalline inclusions. They can be categorized into lesions with predominant intracellular crystals (light chain [LC] proximal tubulopathy, LC crystal-storing histiocytosis, LC crystalline podocytopathy] and lesions with predominant extracellular crystals (crystalglobulin-induced nephropathy, crystalline variant of LC cast nephropathy). The majority of these lesions are associated with low tumor burden lymphoproliferative disorders, with the exception of crystalline variant of LC cast nephropathy. Extra-renal involvement (eg, skin, cornea) is frequent. Kidney biopsy is the cornerstone for diagnosis, which often requires electron microscopy and antigen retrieval. A thorough hematologic workup and evaluation of extra-renal involvement is mandatory for management. Treatment of these lesions is with clone-directed therapy, with the goal of achieving hematologic very good partial response or complete response which preserve or improve kidney function. In vitro and in vivo studies, animal models, and novel sequencing techniques have been invaluable tools to understand the pathogenesis of LC proximal tubulopathy, and can be utilized to increase our limited knowledge of the pathogenesis of the other MIg crystalline nephropathies. This review will provide an update on the pathology, renal and hematologic characteristics, extra-renal manifestations, prognosis, treatment, and pathogenesis of MIg crystalline nephropathies.