Rare Diseases: MGRS and Amyloidosis Course

Monoclonal gammopathies (MG) represent a varied group of diseases that have in common the clonal production of an immunoglobulin or fragment thereof. The monoclonal immunoglobulin (MIg) is produced by a clone of B cells, plasma cells, or lymphoplasmacytic cells and can be present in its intact form or as fragments (light, heavy, or a light and heavy chain). Systemic amyloidoses are also a rare and heterogenous group of diseases that result from the ability of certain proteins to misfold and polymerize into insoluble amyloid fibrils.  These fibrils are deposited in the extracellular space of tissues and organs causing  tissue damage and significant morbidity and even mortality. Amyloidosis is named by their native protein and is often classified by whether it is wild type (acquired) or the result of a germline pathogenic variant (mutant). 

Both MG and amyloidosis affect the kidney.  In the absence of hematological malignancy,  patients with a MIg in the serum and/or urine in combination with kidney involvement, are considered to have a “monoclonal gammopathy of renal significance”  (MGRS). This categorization addresses a therapeutic gap as patients not meeting criteria for overt multiple myeloma were traditionally not treated, (except for AL amyloidosis and monoclonal immunoglobulin deposition disease (MIDD)). Beside AL amyloidosis the most common amyloidogenic proteins that can affect the kidneys include transthyretin (ATTR), beta-2 microglobulin (Aβ2M), serum amyloid A (AA) amyloid and leukocyte cell derived chemotaxin 2 amyloidosis (ALECT2). 

 
At the end of this course participants should be able to: 
Define the different types of MGRS and  of amyloidosis affecting the kidney and estimate their prevalence 
Describe the pathogenesis of MGRS and of amyloidosis-related kidney disease 
Discuss the diagnostic evaluation of patients with MGRS and patients with different types of amyloidosis 
Illustrate the current principles of management of MGRS and the different types of amyloidosis affecting the kidney and the role of kidney transplantation