title: Diagnosis of monoclonal gammopathy of renal significance.
abstract: Monoclonal gammopathy of renal significance (MGRS) regroups all renal disorders caused by a monoclonal immunoglobulin (MIg) secreted by a nonmalignant B-cell clone. By definition, patients with MGRS do not meet the criteria for overt multiple myeloma/B-cell proliferation, and the hematologic disorder is generally consistent with monoclonal gammopathy of undetermined significance (MGUS). However, MGRS is associated with high morbidity due to the severity of renal and sometimes systemic lesions induced by the MIg. Early recognition is crucial, as suppression of MIg secretion by chemotherapy often improves outcomes. The spectrum of renal diseases in MGRS is wide, including old entities such as AL amyloidosis and newly described lesions, particularly proliferative glomerulonephritis with monoclonal Ig deposits and C3 glomerulopathy with monoclonal gammopathy. Kidney biopsy is indicated in most cases to determine the exact lesion associated with MGRS and evaluate its severity. Diagnosis requires integration of morphologic alterations by light microscopy, immunofluorescence (IF), electron microscopy, and in some cases by IF staining for Ig isotypes, immunoelectron microscopy, and proteomic analysis. Complete hematologic workup with serum and urine protein electrophoresis, immunofixation, and serum-free light-chain assay is required. This review addresses the pathologic and clinical features of MGRS lesions, indications of renal biopsy, and a proposed algorithm for the hematologic workup.
authors.affiliation: Department of Nephrology and Transplantation, Centre Hospitalier Universitaire de Poitiers and Centre national de référence maladies rares: amylose AL et autres maladies à depots d'immunoglobulines monoclonales; Université de Poitiers, Poitiers, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Bridoux
authors.affiliation: 1] Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA [2] Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Nelson
authors.initials: N
authors.lastname: Leung
authors.affiliation: Department of Medicine, University of Otago, Wellington, New Zealand.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hutchison
authors.affiliation: Department of Nephrology and Transplantation, Centre Hospitalier Universitaire de Poitiers and Centre national de référence maladies rares: amylose AL et autres maladies à depots d'immunoglobulines monoclonales; Université de Poitiers, Poitiers, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Touchard
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Department of Hematology and Immunology, Univerisity Hospital St Louis, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fermand
authors.affiliation: Department of Pathology, Loyola University Medical Center, Maywood, Illinois, USA.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Picken
authors.affiliation: Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Herrera
authors.affiliation: Department of Clinical Therapeutics, Alexandra Hospital, University of Athens School of Medicine, Athens, Greece.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
authors.affiliation: Hématologie Clinique, Hôpital Purpan, Toulouse, France.
authors.forename: Murielle
authors.initials: M
authors.lastname: Roussel
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Samih H
authors.initials: SH
authors.lastname: Nasr
mesh_terms: D000465:Algorithms; D001706:Biopsy; D006403:Hematologic Tests; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood; D007136:Immunoglobulins / Q000097:blood* / Q000652:urine; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000150:complications* / Q000175:diagnosis*
chemical_list: D007147:Immunoglobulin Light Chains; D007136:Immunoglobulins