title: Spectrum of manifestations of monoclonal gammopathy-associated renal lesions.
abstract: OBJECTIVE
  Monoclonal gammopathies result from an overt malignant process, such as multiple myeloma, or a premalignant process, such as monoclonal gammopathy of undetermined significance. The kidney is often affected in the setting of a monoclonal gammopathy. The term 'monoclonal gammopathy of renal significance (MGRS)' was recently introduced to draw attention to renal diseases related to the monoclonal gammopathy. In this review, we define the pathology of these monoclonal gammopathy-associated kidney diseases.
  
  
  RESULTS
  Renal disease can be caused by deposition of the monoclonal immunoglobulin (direct mechanism) or by activation of the alternative pathway of complement by the monoclonal immunoglobulin (indirect mechanism). The deposition of monoclonal immunoglobulin can affect the glomeruli, tubules, and the interstitium and vessels. The glomerular diseases include proliferative glomerulonephritis with monoclonal immunoglobulin deposits, immunotactoid glomerulopathy, and, less commonly, fibrillary glomerulonephritis. Tubular lesions associated with monoclonal immunoglobulin include cast nephropathy and light-chain proximal tubulopathy. Lesions involving the glomeruli, tubules, interstitium or vessels include amyloidosis and monoclonal immunoglobulin deposition diseases. Rarely, monoclonal immunoglobulin may also cause C3 glomerulopathy or atypical hemolytic uremic syndrome by interfering with the regulation of the alternative pathway of complement.
  
  
  CONCLUSIONS
  Monoclonal gammopathy are associated with a variety of kidney diseases. The monoclonal gammopathy-associated renal diseases are distinct in their pathogenesis, kidney biopsy findings, clinical presentation, progression, prognosis, and treatment. The term monoclonal gammopathy of renal significance helps highlight patients who have renal disease secondary to monoclonal immunoglobulin secreted by a premalignant or malignant clone, but is not a disease or diagnosis in itself.
authors.affiliation: aDivision of Anatomic Pathology, Department of Laboratory Medicine and Pathology bDivision of Hypertension and Nephrology, Department of Internal Medicine cDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sethi
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
mesh_terms: D003176:Complement C3 / Q000378:metabolism; D003450:Cryoglobulins / Q000378:metabolism; D005921:Glomerulonephritis / Q000473:pathology; D015614:Histiocytosis / Q000473:pathology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007674:Kidney Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D010265:Paraproteinemias / Q000150:complications* / Q000378:metabolism
chemical_list: D003176:Complement C3; D003450:Cryoglobulins; D007136:Immunoglobulins