Successful treatment with bortezomib and dexamethasone for proliferative glomerulonephritis with monoclonal IgG deposits in multiple myeloma: a case report

Abstract

Background: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a form of renal involvement by monoclonal IgG deposits that was found in mesangial, subendothelial or subepithelial regions. The distribution of glomerular deposits was completely different from that in monoclonal immunoglobulin deposition disease. PGNMID is reported to be rarely associated with a hematological malignancy. Previously, only five cases of PGNMID with multiple myeloma have been reported. However, the pathogenic relationship between PGNMID and multiple myeloma was unclear because a detailed description was not provided. We report that a patient with PGNMID associated with multiple myeloma was treated with bortezomib and dexamethasone and underwent the second renal biopsy after treatment, showing that chemotherapy was effective for PGNMID clinically and pathologically.

Case presentation: A 75-year-old man presented with progressive leg edema, had nephrotic range proteinuria, hypoalbuminemia, moderate renal failure, and occult blood in his urine. Electrophoresis results showed serum and urinary monoclonal spikes of IgGκ type immunoglobulin. A renal biopsy specimen showed lobular mesangial proliferation with mesangiolysis, glomerular micro-aneurysm, and endocapillary hypercellularity. Immunofluorescence results revealed strong granular capillary and mesangial staining for IgG1, C3 and κ light chain in glomeruli without tubular deposits of any immunoglobulin. Electron microscopy also showed dense granular deposits in subendothelial and mesangial areas. PGNMID associated with multiple myeloma (IgGκ type) was diagnosed on the basis of a subsequent bone marrow examination. Bortezomib and dexamethasone therapy significantly reduced proteinuria and elevated serum albumin level. Eight months later, the second renal biopsy showed no active lesions and that the IgG1 and κ light chain deposits had drastically disappeared.

Conclusions: This is the first case of PGNMID with multiple myeloma successfully treated with bortezomib and dexamethasone in which comparative renal biopsies were performed before and after treatment. Our findings suggest the pathogenesis of PGNMID and therapeutic options for PGNMID.

Keywords: Monoclonal gammopathy; Multiple myeloma; Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID).

Fig. 1

Renal biopsy histological features of PGNMID associated with multiple myeloma. First renal biopsy (a-k). a Periodic acid-Schiff (PAS) staining: renal histopathology showed lobular glomeruli with mesangial expansion and cell proliferation complicated with acute lesions, such as mesangiolysis, ×200. b Hematoxylin and eosin (HE) staining: glomerular micro-aneurysm and endocapillary hypercellularity, ×400. c Periodic acid methenamine silver (PAM) staining: duplication of glomerular basement membrane (an arrow) and mesangiolysis (an arrow head) was observed, ×1000. Congo red staining was negative (not shown). d Immunoglobulin G (IgG), e immunoglobulin G1 (IgG1), and f kappa immunostaining were detected on capillary walls and mesangial areas. (g) Lambda immunostaining was negative. h C3 immunofluorescence was positive (2+) on capillary walls, and (i) C1q was also weakly positive (1+) on some capillary walls. No positive immunofluorescence was found in tubular basement membranes. Staining for IgM and IgA was negative (not shown). IgG subclass analysis was positive for IgG1 only. IgG2, IgG3, and IgG4 were negative (not shown). EM (j) low-power and (k) high-power fields showed that electron-dense deposits in the subendothelial and mesangial areas exhibited a granular texture without a fibrillary appearance. Second renal biopsy (l-v). l Glomeruli showed less of an increase in mesangial matrix in the first renal biopsy and no mesangiolysis or micro-aneurysms with PAS staining, ×100. m A glomerulus showed no endocapillary hypercellularity with HE staining, ×400. n A glomerulus still had partial duplication of the glomerular basement membrane with PAM staining, ×1000. o IgG, (p) IgG1, (q) kappa, and (r) lambda immunofluorescence results were negative. (s) C3 immunofluorescence was weakly positive in a mesangial area. (t) No deposition of C1q. EM (u) low-power and (v) high-power fields showed no electron-dense deposits

Fig. 2

Clinical course. After initiating prednisolone therapy, this patient underwent four cycles of BD therapy (bortezomib at 1.3 mg/m²/week, and dexamethasone at 20 mg/week), followed by bortezomib maintenance therapy (1.3 mg/m², biweekly). The κ/λ ratio, urinary protein (UP), and eGFR (calculated using equations for Japanese [26]) results are shown over the course of treatment