Favorable effect of bortezomib in dense deposit disease associated with monoclonal gammopathy: a case report

Abstract

BackgroundComplement component 3 (C3) glomerulopathy, which includes dense deposit disease (DDD) and C3 glomerulonephritis, is caused by dysregulation of the alternative complement pathway. In most cases, C3 glomerulopathy manifests pathologically with membranoproliferative glomerulonephritis-like features. An association between C3 glomerulopathy and monoclonal gammopathy was recently reported in several cases, raising the possibility that C3 glomerulopathy is the underlying pathological process in monoclonal gammopathy of renal significance.Case presentationWe herein report a case of monoclonal gammopathy-induced DDD that improved histologically and clinically with chemotherapy including bortezomib. Our case is the first in which treatment response can be linked to the histological response. Potential pathological insights are also discussed.ConclusionsRapid and efficient chemotherapy has the potential to limit renal damage in monoclonal gammopathy-associated DDD.

Monoclonal immunoglobulin mediates complement activation in monoclonal gammopathy associated-C3 glomerulonephritis

“…DDD: 1; C3GN: 24Conservative: 13; immunosuppressive therapy: 8; clone-directed chemotherapy: 29 (including bortezomib in 22 patients)ESRD: 25 (9 in the chemotherapy group)IgGλ: 11Smouldering MM: 15FHAA: 9IgAκ: 1Symptomatic MM: 2a rare variant of undetermined significance (p. D130N in CFH and p. E548Q in CFI): 2IgAλ: 1CLL: 3λ LC only: 1Timmermans [15]2018275.5 (75–76)1/1IgGκ: 1MGUS: 2C3NeF and FHAA were not foundDDD: 1; C3GN: 1Conservative: 2Relatively stable renal function: 1; chronic kidney failure: 1IgGλ: 1Chauvet [13]20184163 (36–83)25/16IgGκ: 27MGRS: 28C3NeF: 3;Electron microscopy was available in 25 cases. DDD: 1; C3GN: 24NANAIgGλ: 11other (MM, CLL): 13FHAA: 9;IgAκ: 2FIAA: 2;κ LC only: 1Anti-CR1 Abs: 11a rare variant of undetermined significance (p. D130N in CFH and p. E548Q in CFI): 2Ravindran [11]20183660 (20–85)25/11IgG: 31MGRS: 26C3NeF: 11/24;DDD: 4; C3GN: 32Conservative: 3; non-targeted therapy: 17; MIg-targeted therapy: 16Complete or partial renal response or stable renal function: 44% of patient with MIg-targeted therapy and 41% of patients with non-targeted therapy.IgM: 3Smouldering MM: 2FHAA: 2/24;IgA: 1Symptomatic MM: 5FBAA: 1/24;κ: 26CLL: 1CFH H402 and/or V62 allele: 13/21λ: 10Cryoglobulinemia (type 1): 1other variants/mutations of unknown C3G pathogenicity: 4/212Cryoglobulinemia (type 2): 1Hirashio [22]20181521/0λ LC: 1MGRSFHAADDD…”

Bortezomib-containing regiment in treating glomerulopathy with fibronectin deposits combined with monoclonal gammopathy of undetermined significance: a case report and literature review

“…Shuma once applied BD regimen containing bortezomib to treat a patient with dense deposit disease (DDD) secondary to MGUS in 2018, and the patient's edema symptoms and renal function were significantly improved. Histological elimination of DDD and serum complement activation were controlled after the second renal biopsy (40). The patient in our case was treated with the BCD regimen for 4 cycles, the clinical edema was completely relieved, and the serum albumin level was close to normal.…”

Use of Bortezomib in the Treatment of C3 Glomerulonephritis Refractory to Eculizumab and Rituximab

“…Thus far, the use of plasma cell targeted therapies such as bortezomib has been limited to renal pathology associated with myeloma, monoclonal gammopathy, or monoclonal immune deposits. [6][7][8] Treatment of C3G associated with nephritic factor or factor H autoantibody, on the other hand, typically involves the use of plasmapheresis, mycophenolate, prednisone, rituximab, and eculizumab. With the exception of rituximab, these therapies do not address the underlying cause of complement dysregulation in autoantibody-associated C3G.…”