The Scope of Kidney Affection in Monoclonal Gammopathies at All Levels of Clinical Significance

Abstract

Multiple myeloma (MM) is one of the most important clonal malignant plasma cell disorders and renal involvement is associated with poor prognosis. Although there are several reasons for renal impairment in MM, the main cause is the toxic effects of monoclonal proteins. Although cast nephropathy is the best known and unchallenged diagnosis for hematologists and pathologists, the renal effects of monoclonal gammopathy can be various. Monoclonal gammopathy of renal significance was proposed by the International Kidney and Monoclonal Gammopathy Research Group for renal lesions in monoclonal gammopathy in recent years. Renal lesions in monoclonal gammopathy can be grouped as follows: light chain (cast) nephropathy, acute tubular injury/necrosis, tubulointerstitial nephritis, amyloidosis, monoclonal Ig deposition diseases, immunotactoid glomerulopathy, type I cryoglobulinemia, proliferative glomerulonephritis with monoclonal IgG deposits, C3 glomerulopathy with monoclonal gammopathy, and crystal-storing histiocytosis, considering the previous and new terminology. In this study, renal involvement of monoclonal gammopathies, in terms of previous and new terminology, was reviewed.

Keywords: Kidney Cast nephropathy.; Monoclonal gammopathy of renal significance; Multiple myeloma; Plasma cell disorders; Renal involvement.

Figure 1. Light chain cast nephropathy: A) classical large myeloma casts show irregular shape and fracture planes (hematoxylin and eosin; 100^x); B) giant cell surrounding the casts (hematoxylin and eosin; 200^x); C) metachromatic staining of the myeloma casts (Masson’s trichrome; 200^x).

Figure 2. Light chain proximal tubulopathy: A) dark positive dots are a clue for the accumulation of light chain protein in proximal tubules (PAMS; 400^x); B) cytoplasmic granular staining with direct immunofluorescence for lambda light chain (fluorescein, 400^x).

Figure 3. Light chain-related tubulointerstitial nephritis: A-B) interstitial lymphocyte-rich inflammation (hematoxylin and eosin; 100^x and 200^x); C) very few cellular cast formations may be the only clue for monoclonal gammopathy (hematoxylin and eosin; 400^x).

Figure 4. AL amyloidosis. Acellular brick red mesangial deposits with Congo red in the glomerulus (A) and also a vessel wall (B) (400x). C) Yellow-orange birefringence in glomerulus and vessels under polarized light with Congo red (200^x). D) Mesangial lambda light chain amyloid deposits with direct immunofluorescence (fluorescein, 400^x).

Figure 5. C3 glomerulopathy with monoclonal gammopathy: A) mesangial matrix expansion (hematoxylin and eosin; 400^x); B) positivity of the mesangial complement C3c with direct immunofluorescence (fluorescein, 400^x).

Schema 1. MGRS-associated renal lesions (modified from Bridoux et al. [36]). AH: Immunoglobulin heavy chain amyloidosis, AHL: immunoglobulin heavy and light chain amyloidosis, AL: immunoglobulin light chain amyloidosis, GN: glomerulonephritis, HCDD: heavy chain deposition disease, LCDD: light chain deposition disease, LHCDD: light and heavy chain deposition disease, MGRS: monoclonal gammopathy of renal significance.