Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification

Sethi S.;Beck L. H.;Glassock R. J.;Haas M.;De Vriese A. S.;Caza T. N.;Hoxha E.;Lambeau G.;Tomas N. M.;Madden B.;Debiec H.;D'Agati V. D.;Alexander M. P.;Amer H.;Appel G. B.;Barbour S. J.;Caravaca-Fontan F.;Cattran D. C.;Casal Moura M.;D'Avila D. O.;Eick R. G.;Garovic V. D.;Greene E. L.;Herrera Hernandez L. P.;Jennette J. C.;Lieske J. C.;Markowitz G. S.;Nath K. A.;Nasr S. H.;Nast C. C.;Pani A.;Praga M.;Remuzzi G.;Rennke H. G.;Ruggenenti P.;Roccatello D.;Soler M. J.;Specks U.;Stahl R. A. K.;Singh R. D.;Theis J. D.;Velosa J. A.;Wetzels J. F. M.;Winearls C. G.;Yandian F.;Zand L.;Ronco P.;Fervenza F. C.

2023-01-01

---

Abstract

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.