The history of membranous nephropathy (MN) dates back to the 1940s, although it began with a different name. In 1947 E.T. Bell published a book on different types of renal diseases and included one illness that he called membranous glomerulonephritis. He explained that the disease manifested as a thickening of the glomerular basement membrane (GBM). In addition, he wrote that it was clinically characterized by marked proteinuria and edema.
In 1957, the first evidence of the difference of this condition from others that it was grouped with appeared by David Jones, a renal pathologist from Syracuse University. During his study, Jones used a special stain called periodic acid-silver methenamine to separate membranous glomerulonephritis as a distinct morphological entity.
Through his work, Jones showed how the features of membranous glomerulonephritis lesions were not shared by other lesions, including those from conditions such as lobular glomerulonephritis, lipoid nephrosis, and chronic glomerulonephritis
In addition, by using his special stain, Jones could easily see the thickening of the capillary wall and the alteration of the basement membrane structure, which was what was first described by Bell in 1947.
In 1959, the third component unique to lesions of membranous glomerulonephritis was identified. Movat and McGregor, using electron microscopic methods, identified the electron-dense subepithelial location of the deposits that occupied the spaces between the altered GBM.
In 1968, Ehrenreich identified and described the four stages of glomerular lesions using repeated renal biopsy. They break down as such:
- Stage I: only a few small subepithelial deposits; GBM may appear normal or only slightly thickened
- Stage II: spikes protruding from the GBM can be observed using staining
- Stage III: the spikes are incorporated within the GBM
- Stage IV: the GBM appears irregularly thickened by reabsorbed deposits
These discoveries of both lesion characteristics and disease stages not only defined MN as a unique type of renal pathology in comparison to the broad grouping Bell originally included it in, but they also helped to shape the development of clinical practices still in use.
The “glomerulonephritis” part of the name membranous glomerulonephritis, originally developed by Bell, suggests glomerular inflammation. However, over time, scientists have found that this condition has a lack of glomerular inflammation, and so have replaced the name with membranous nephropathy.
In the late 1970s, our understanding of membranous nephropathy changed completely. Specifically, the research discoveries changed our knowledge of how the condition develops. Up until this point, scientists believed that all types of immune-complex glomerulonephritis resulted from circulating immune complexes that were passively trapped in the glomeruli, which is a component of the kidney.
However, in the late 1970s, two research groups studied Heymann nephritis, a rat model of experimental MN. They found that the deposits in experimental MN formed when circulating antibodies bound to a glomerular antigen. Years later, the antigen was identified to be megalin.
While MN was first identified and then analyzed more than 50 years ago, scientists have spent the years since then learning more about the pathology of the condition and what can cause it. This aids in not only the diagnosis but also the treatment of the disease.
References
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921260/
[2] https://pubmed.ncbi.nlm.nih.gov/20378220/
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691064/