Monoclonal Gammopathies of Renal Significance: Renal Biopsy and Beyond

Abstract

Monoclonal Gammopathies of Renal Significance (MGRS) are a rather heterogeneous group of renal disorders caused by a circulating monoclonal (MC) immunoglobulin (Ig) component, often in the absence of multiple myeloma (MM) or another clinically relevant lymphoproliferative disorder. Nevertheless, substantial kidney damage could occur, despite the "benign" features of the bone-marrow biopsy. One example is renal amyloidosis, often linked to a small clone of plasma cells, without the invasive features of MM. However, patients with amyloidosis may present with a nephrotic syndrome and renal failure, eventually leading to end-stage kidney disease. At the same time, other organs, such as the heart and the liver, may be severely damaged by Ig light chains or amyloid deposits, occasionally resulting in fatal arrhythmias and/or organ failure. Acute kidney injury (AKI) may as well result from massive excretion of MC proteins, with deposition disease in glomeruli or renal tubules, not rarely obstructed by luminal aggregates, or "casts". Proliferative glomerulonephritis with monoclonal Ig deposits is another, less frequent clinical presentation of an MGRS. The present review deals with the implications of MGRS for renal function and prognosis, and the potential of tools, such as the renal biopsy, for assessing clinical risk and guiding therapy of the underlying condition.

Keywords: amyloidosis; immunoglobulins; kidney; light chains; monoclonal gammopathies; myeloma; renal biopsy.

Figure 1

Basic structure of a human immunoglobulin. In the upper panels, the five isotypes, including dimeric IgA and pentameric IgM. See text for details.

Figure 2

(A,B) AL Amyloidosis, IgG λ. Amyloid deposits in the mesangium with haphazardly arranged fibrils, ∅ ÷8.5 nm. (C,D) AL Amyloidosis, IgA λ. Amyloid deposits along the capillary loops with haphazardly arranged fibrils, ∅ ÷7.6 nm. (E,F) AL Amyloidosis, IgA λ. Bundles of amyloid fibrils forming “haystacks” perpendicular to the GBM (same case as in (C,D)). (G,H) AL Amyloidosis, IgG κ in B-cell lymphoma. Amyloid deposits causing podocyte foot process effacement and widening of basement membranes with randomly arranged and nonbranching fibrils, ∅ 8 nm. Transmission Electron Microscopy, uranyl acetate; Morgagni 268D TEM–FEI, Hillsboro, OR, USA. Abbreviations: GMB, glomerular basement membrane; MM, multiple myeloma. The fibrillar pattern of this area (*) is shown magnified in the micrograph(s) on the right side.

Figure 3

(A,B) LCDD, IgG λ. Fibrillary deposits in the subepithelial region of capillary wall, with straight fibrils over a lucent background, ∅ ÷12.5 nm. Congo Red stain was negative. (C,D) Cast nephropathy, IgG κ MM. Scant deposits in the mesangial matrix with fibrils also organized in parallel arrays, ∅ ÷15 nm. (E,F) LCDD, IgG κ. Band-like deposition of electron-dense granular material running along the GBM (black arrowheads). Transmission Electron Microscopy, uranyl acetate; Morgagni 268D TEM–FEI, Hillsboro, OR, USA. Abbreviations: GMB, glomerular basement membrane; LCDD, light chain deposition disease; MM, multiple myeloma; The fibrillar pattern of this area (*) is shown magnified in the micrograph(s) on the right side.