Treatment of membranous nephropathy: Time for a paradigm shift

Piero Ruggenenti, Fernando Custodio Fervenza, Giuseppe Remuzzi

Research output: Contribution to journalReview article

32 Citations (Scopus)

Abstract

In patients with membranous nephropathy, alkylating agents (cyclophosphamide or chlorambucil) alone or in combination with steroids achieve remission of nephrotic syndrome more effectively than conservative treatment or steroids alone, but can cause myelotoxicity, infections, and cancer. Calcineurin inhibitors can improve proteinuria, but are nephrotoxic. Most patients relapse after treatment withdrawal and can become treatment dependent, which increases the risk of nephrotoxicity. The discovery of nephritogenic autoantibodies against podocyte M-type phospholipase A2 receptor (PLA 2 R) and thrombospondin type-1 domain- containing protein 7A (THSD7A) antigens provides a clear pathophysiological rationale for interventions that specifically target B-cell lineages to prevent antibody production and subepithelial deposition. The anti-CD20 monoclonal antibody rituximab is safe and achieves remission of proteinuria in approximately two-thirds of patients with membranous nephropathy. In those with PLA 2 R-related disease, remission can be predicted by anti-PLA 2 R antibody depletion and relapse by antibody re-emergence into the circulation. Thus, integrated evaluation of serology and proteinuria could guide identification of affected patients and treatment with individually tailored protocols. Nonspecific and toxic immunosuppressive regimens will fall out of use. B-cell modulation by rituximab and second-generation anti-CD20 antibodies (or plasma cell-targeted therapy in anti-CD20 resistant forms of disease) will lead to a novel therapeutic paradigm for patients with membranous nephropathy.

Original languageEnglish (US)
Pages (from-to)563-579
Number of pages17
JournalNature Reviews Nephrology
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2017

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Membranous Glomerulonephritis
Phospholipase A2 Receptors
Proteinuria
B-Lymphocytes
Steroids
Thrombospondin 1
Chlorambucil
Therapeutics
Recurrence
Podocytes
Antibodies
Poisons
Alkylating Agents
Nephrotic Syndrome
Cell Lineage
Serology
Immunosuppressive Agents
Cell- and Tissue-Based Therapy
Plasma Cells
Autoantibodies

ASJC Scopus subject areas

  • Nephrology

Cite this

Treatment of membranous nephropathy : Time for a paradigm shift. / Ruggenenti, Piero; Fervenza, Fernando Custodio; Remuzzi, Giuseppe.

In: Nature Reviews Nephrology, Vol. 13, No. 9, 01.09.2017, p. 563-579.

Research output: Contribution to journalReview article

Ruggenenti, Piero ; Fervenza, Fernando Custodio ; Remuzzi, Giuseppe. / Treatment of membranous nephropathy : Time for a paradigm shift. In: Nature Reviews Nephrology. 2017 ; Vol. 13, No. 9. pp. 563-579.
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