Dysproteinemias and glomerular disease

Nelson Leung, Maria E. Drosou, Samih H. Nasr

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells fromthe B cell lineage. The resultant monoclonal protein can be composed of the entire Ig or its components. Monoclonal proteins are increasingly recognized as a contributor to kidney disease. They can cause injury in all areas of the kidney, including the glomerular, tubular, and vascular compartments. In the glomerulus, the major mechanism of injury is deposition. Examples of this include Ig amyloidosis, monoclonal Ig deposition disease, immunotactoid glomerulopathy, and cryoglobulinemic GN specifically from types 1 and 2 cryoglobulins. Mechanisms that do not involve Ig deposition include the activation of the complement system, which causes complement deposition in C3 glomerulopathy, and cytokines/growth factors as seen in thrombotic microangiopathy and precipitation, which is involved with cryoglobulinemia. It is important to recognize that nephrotoxic monoclonal proteins can be produced by clones from any of the B cell lineages and that amalignant state is not required for the development of kidney disease. The nephrotoxic clones that do not meet requirement for a malignant condition are now called monoclonal gammopathy of renal significance. Whether it is a malignancy or monoclonal gammopathy of renal significance, preservation of renal function requires substantial reduction of the monoclonal protein. With better understanding of the pathogenesis, clone-directed strategies, such as rituximab against CD20 expressing B cell and bortezomib against plasma cell clones, have been used in the treatment of these diseases. These clone-directed therapies been found to be more effective than immunosuppressive regimens used in nonmonoclonal protein–related kidney diseases.

Original languageEnglish (US)
Pages (from-to)128-139
Number of pages12
JournalClinical Journal of the American Society of Nephrology
Issue number1
StatePublished - Jan 6 2018


  • Amyloidosis
  • B-Lymphocytes
  • Cytokines
  • Dysproteinemia
  • Glomerular disease
  • Glomerulonephritis
  • Immunoglobulins
  • Kidney
  • Kidney diseases
  • Kidney glomerulus
  • MGRS
  • Monoclonal gammopathy
  • Paraproteinemias
  • Thrombotic microangiopathies

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation


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