A case of heavy-chain deposition disease with good long-term renal survival and a literature review

Abstract

Background: Monoclonal immunoglobulin deposition disease (MIDD) is characterized by the deposition of nonamyloid monoclonal immunoglobulin and its free fragment light chain and/or heavy chain in systemic tissues and organs, and the kidney is most vulnerable organs. MIDD can be divided into three types: light-chain deposition disease (LCDD), light and heavy chain deposition disease (LHCDD), and heavy-chain deposition disease (HCDD), of which LHCDD and HCDD are rarer (Bridoux et al. in Kidney Int 2015;87:698-711; Preud'homme et al. in Kidney Int 1994;46:965-72). Poor outcome in most HCDD, but in this paper, we will report a case of HCDD with good long-term renal survival and review the literature for reference.

Case presentation: A 32-year-old man presented to our department with skin laxity and nephritic syndrome, accompanied by an significant increase of serum creatinine and received short-term hemodialysis treatment. Both the blood and urine free light chain ratio increased significantly. Renal biopsy showed mesangial nodular glomerulosclerosis on light microscopy, and immunofluorescence staining showed positivity for γ-heavy chain (HC), with negative light chain (LC) staining; the diagnosis was considered HCDD. After six courses of bortezomib combined with dexamethasone chemotherapy and thalidomide 100 mg/day, the renal function gradually recovered, while also with proteinuria and hematuria significantly improved. The blood and urine free light chain ratio decreased to normal. Until now, the patient has been followed for four years, and long-term renal survival has been observed.

Conclusion: Herein, we report a case presenting with proteinuria, hematuria, renal impairment, and skin laxity, and a renal biopsy showed linear IgG deposition in the glomerular basement membranes and tubular basement membrane. However, they ultimately proved to have HCDD. Bortezomib combined with dexamethasone, and oral thalidomide led to a good long-term renal survival. We also provide a review of currently available literature, and this is the first large-scale review summarizing the characteristics of HCDD up to date.

Keywords: Acute renal failure; Case report; Heavy-chain deposition disease; Monoclonal immunoglobulin deposition disease; Skin laxity.

Fig. 1

Skin laxity in the face, neck and abdomen of the patient. A and C before treatment. B and D 44 months after the first treatment

Fig. 2

Light microscopy. A. Hematoxylin-eosin staining (×100); B. Periodic acid-Schiff staining (×200); showing moderate-to-severe proliferation of glomerular mesangial cells and matrix; C. Periodic acid-silver methenamine (×200); showing crescent formation (*) and glomerular basement membrane thickening, segmental mesangial insertion, and double-track formation (white arrow); D. Masson’s trichrome staining (×400); showing nodular glomerulosclerosis

Fig. 3

Immunofluorescence staining shows: IgG(+++), IgA(-), IgM(+), C3(++), Clq(-), κ(-), λ(-), IgG1(-), IgG4(-), PLA2R(-). IgG in a linear deposition in glomerular and tubular basement membranes (A) (×200). Moderate positivity for γ heavy chain in a linear deposition in glomerular basement membrane (B) (×100) and tubular basement membrane (C) (×200). Free light chain κ (D) (×100) and λ (E) (×100) are negative. Immunohistochemistry κ (F) and λ (G) are negative

Fig. 4

Electron microscopy shows segmental thickening of glomerular basement membrane, extensive fusion of foot processes (B ×12,000), significant proliferation of mesangial cells and matrix, and nodule formation. The mesangial area, the medial basement membrane of the glomerulus (A ×15,000 and B ×12,000), and the lateral basement membrane of the renal tubule (C ×8000) showed a lot of granular amorphous electron density