Membranous nephropathy is a type of glomerulonephritis in which autoantibodies to an antigen on the surface of the podocyte lead to severe nephrotic syndrome, and often progressive sclerosis of glomeruli.
UK centres making substantial contributions to our understanding of the pathogenesis, clinical course, and management of membranous nephropathy (MN) have included Guy’s and Bristol, but especially Manchester.
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From the 1970s onwards both Guy’s (Stewart Cameron) and Manchester (Netar Mallick) realised the value of large cohorts of patients with defined glomerular pathology, careful clinical and lab documentation, and prolonged follow up. The MN cohorts yielded for example the first much quoted report of an association between MN and malignancy (Guy’s) [1] and a description of MN with relapsing nephrotic syndrome (Manchester) [2].
Manchester reported the unusual phenomenon of familial membranous nephropathy in three twin pairs, one monozygotic [3]. Mallick also built a collaboration with the genetics group in Manchester (Rodney Harris with Peter Klouda), which had experience in immunogenetics focused on genetic variations in HLA. This was an era when HLA typing was predominantly based on serological and cell based methodology and genetic studies used techniques much less specific than modern molecular approaches. Nevertheless, Manchester’s worldwide first in reporting an association between HLA-DRW3 and membranous nephropathy in Caucasians [4] has stood the test of time, confirmed in larger cohorts using more refined techniques.
The UK also completed two randomised controlled trials in MN funded by MRC. Both studied subjects with MN and heavy proteinuria and therefore at high risk of progression. An early trial led by Stewart Cameron provided evidence that corticosteroids alone gave no significant clinical benefit [5]. The second led by Peter Mathieson (Bristol) some twenty years later addressed, in MN at high risk of progression, the relative benefits and toxicity of the ‘Ponticelli regimen’ (corticosteroids with cyclophosphamide) or cyclosporin, compared with supportive care [6]. It indicated that better outcomes were achieved with corticosteroids and cyclophosphamide, although associated with more serious adverse events compared to supportive care.
Work in Manchester identified urinary excretion of complement activation fragments (C3dg and C5b-9) as a useful marker of active disease [7]; although this never went on to enter routine clinical practice.
In the 1980s Manchester became the leading UK centre for study of the pathogenesis of MN, and one of small number of groups around the world directing their efforts to identify the autoantigen(s) involved in the pathogenesis of MN. The work was started by Netar Mallick, who was soon joined by in the late 1970s by Paul Brenchley, Colin Short, and Beatrice Coupes, who with others continued the work after Mallick’s retirement in 2000.
Read Paul Brenchley’s account of Manchester’s achievements.
The global interest in understanding MN led to Manchester hosting the 1st International Symposium on Membranous Nephropathy in 1990 at the Whitworth Art Gallery in Manchester. This was attended by the leading researchers in all aspects of MN from across Europe and USA.
Figure. 1st International Symposium on Membranous Nephropathy, Manchester 1990
Back row: Dontscho Kerjaschki (Vienna), Phil Dyer (Manchester), Colin Short (Manchester), Pietro Zucchelli (Bologna), Beppe d’Amico (Milan), Jim Donadio (Mayo Clinic, Rochester), Bill Couser (Seattle), Eric Honkanen (Helsinki)
Middle row: Dan Cattran (Toronto), Paul de Jong (Groningen), Pierre Ronco (Paris) Beatrice Coupes (Manchester), Priscilla Kincaid-Smith (Melbourne), Richard Glassock (Los Angeles), Netar Mallick (Manchester).
Front row: ??, Paul Brenchley (Manchester), Stewart Cameron (Guy’s), Linda Hunt (Manchester), Sandy Davison (Leeds), Claudio Ponticelli (Milano), Alan Meyrier (Paris)
John Feehally. First published July 2024.
Last Updated on September 17, 2024 by neilturn