Kidney disease and multiple myeloma

Abstract

Kidney injury is a common complication of multiple myeloma and other plasma cell dyscrasias, and it is associated with increased mortality. Multiple pathogenic mechanisms can contribute to kidney injury in the patient with myeloma, some of which are the result of nephrotoxic monoclonal Ig and some of which are independent of paraprotein deposition. The pathogenic mechanisms that underlie paraprotein-related kidney disease are increasingly well understood. A novel assay allowing the quantification of free light chains in the serum has aided the diagnosis of new onset disease and allowed for the earlier detection of relapse. Novel myeloma agents have shown considerable promise in reversing renal failure in some patients and improving outcomes. Stem cell transplantation remains a mainstay of management for younger patients with myeloma who are suitable candidates for intensive therapy, whereas the role of new drugs, plasma exchange, and kidney transplantation continues to evolve.

Figure 1.

Light chain cast nephropathy (also known as myeloma kidney). (A) The tubules contain eosinophilic proteinaceous casts that have a crystalline and broken appearance. Notice the prominent inflammatory reaction with foreign body type multinucleated giant cells in close proximity to the cast material (hematoxylin and eosin-stained section). (B) The electron microscopy shows the characteristic electron-dense cast material inside a tubule. The conditions in the tubule have facilitated the organization of the light chain into a supramolecular crystal-like structure. (C) The immunofluorescence microscopy with fluoresceinated anti–λ-antibodies shows strong staining of the cast for this light chain. Notice the high background staining of the tissue for the λ-light chain, a reflection of the higher plasma and hence, tissue concentration of this protein. (D) The staining of the casts for κ-light chains is negative. Also, the staining of the background for this light chain is significantly weaker than for λ-light chains.

Figure 2.

Systemic κ-light chain deposition disease. (A) The glomerulus reveals a distinctive nodular appearance caused by expansion of the mesangial matrix in response to the deposition of the paraprotein (periodic acid–Schiff-stained section). Notice the thickening of the tubular basement membranes and prominent interstitial fibrosis. (B) The electron microscopy shows characteristic confluent and fine granular Randall-type dense deposits along the inner aspect of the wrinkled glomerular basement membranes. The endothelium has been damaged by this process and is missing from this segment of the capillary loop. (C) By immunofluorescence microscopy with fluoresceinated anti–κ-antibodies, all basement membranes and the mesangial nodules show strong staining for this light chain. (D) The staining of the basement membranes and the mesangial nodules for λ-light chains is significantly weaker and near background. The staining for all heavy chains is likewise negative (not shown).

Figure 3.

Light chain amyloid (AL) with λ-light chain specificity, with involvement of glomeruli (Glom) and arteries (Art). (A) The Congo red stain reveals orange-red deposits expanding the mesangium and infiltrating the peripheral capillary walls of the Glom and the Art. (B) Amyloid deposits show characteristic apple-green birefringence when viewed under polarized light. Only those amyloid aggregates with fibrils in a particular angle of orientation show green birefringence at any given position of the polarizing filters. As one rotates the slide on the microscope stage, green birefringence of the amyloid deposits with fibrils at the various angles of orientation within the tissue will be revealed. (C) Immunofluorescence microscopy with fluoresceinated anti–λ-antibodies shows strong staining of the coarse and confluent amyloid deposits in the Glom and the wall of the Art. (D) The reactivity of the amyloid is negative for κ-light chains as revealed with the fluoresceinated anti–κ-light chain reagent.