Renal monoclonal immunoglobulin deposition disease (MIDD): the Columbia experience

Abstract

Renal manifestations of plasma cell dyscrasia are diverse and include AL amyloidosis, myeloma cast nephropathy, monoclonal immunoglobulin deposition disease, light chain Fanconi syndrome, cryoglobulinemic glomerulonephritis, and renal infiltration by lymphoplasmacytic malignancies. The non-amyloidotic monoclonal immunoglobulin deposition diseases (MIDD) are a family of related disorders that share the clinical-pathologic features of nodular sclerosing glomerulopathy, nephrotic proteinuria, and renal insufficiency¹. These entities are defined by the deposition within renal basement membranes of monoclonal light and/or heavy chains, producing a characteristic linear immunofluorescence pattern in all renal compartments. The three subtypes of MIDD include light chain (LCDD)^2–4, light and heavy chain (LHCDD)^5–6, and heavy chain deposition diseases (HCDD)^7–10. LCDD comprises the vast majority of cases, with relatively few examples of LHCDD and HCDD¹¹. The lower reported incidence of LHCDD and HCDD may depend to some extent on the pathologist’s familiarity with these entities and the diagnostic accuracy of the pathologic interpretation. Over 80% of LCDD manifest renal deposits of k light chain. Cases of HCDD have included examples of γ1, γ2, γ3, γ4 and α-heavy chain subtypes^7–10,12. In all the cases of HCDD reported to date there is a common deletion of the CHI constant domain of the γ heavy chain^13,14.