Bridging the Divide: An Onco-Nephrologic Approach to the Monoclonal Gammopathies of Renal Significance

Abstract

The monoclonal gammopathies of renal significance (MGRS) are a group of disorders characterized by monoclonal Ig deposition in the kidney, but are not associated with systemic lymphoma or overt multiple myeloma. The prevailing hypothesis is that the pathogenic paraproteins in MGRS are produced by underlying B cell or plasma cell clones. However, in the MGRS literature, the yield of detecting a clone has been variable, and progression to ESRD is common. Here, we present an "onco-nephrologic" approach to the MGRS disorders by highlighting recent advances in lymphoma and multiple myeloma that can be used in the evaluation and management of these patients.

Keywords: B-Lymphocytes; Chronic; Humans; Kidney Failure; Lymphoma; Myeloma Proteins; Paraproteinemias; Paraproteins; Plasma Cells; glomerular disease; kidney; multiple myeloma; multiple myeloma M-proteins; proteinuria.

Figure 1.

Immunotactoid glomerulopathy. (A) Light microscopy demonstrates massive expansion of the mesangium and capillary walls with eosinophilic material (hematoxylin and eosin stain; original magnification, ×200). (B) Electron microscopy shows fibrillar and microtubular electron-dense deposits in parallel and herringbone-like arrays, with average fibril diameter approximately 35 nm (transmission electron micrograph; original magnification, ×20,000); immunohistochemistry is (C) negative for λ and (D) positive for κ in the mesangium and capillary walls (immunoperoxidase stain; original magnification, ×200). Original figure provided courtesy of Dr. Matthew Palmer, Department of Pathology and Laboratory Medicine, University of Pennsylvania.

Figure 2.

Proliferative GN with monoclonal IgGκ deposits. (A) Light microscopy shows mesangial proliferation and sclerosis with segmental endocapillary and membranoproliferative changes (periodic acid–Schiff stain; original magnification, ×400); immunofluorescence shows positive mesangial and capillary wall staining for (B) IgG heavy chain and (C) κ light chain, while (D) λ light chain is negative (direct immunofluorescence; original magnification, ×400). Original figure provided courtesy of Matthew Palmer, Department of Pathology and Laboratory Medicine, University of Pennsylvania.

Figure 3.

The types of clones identified in MGRS in the major case series. ITGN, immunotactoid glomerulopathy; LCDD, light chain deposition disease; MIDD, monoclonal Ig deposition disease; PGNMID, proliferative GN with monoclonal Ig deposits. Data from previously published studies (–7,15).