Diabetes complications and the renin-angiotensin system.


n engl j med 361;1 nejm.org july 2, 2009 83 ing, as observed in other chronic autoimmune diseases.11 Serial examination of serum samples obtained and stored years before the apparent onset and diagnosis of membranous nephropa­ thy should be enlightening in testing this hy­ pothesis.12 Better understanding of the potential autolo­ gous or environmental triggers of autoantibody production in patients with membranous nephrop­ athy may uncover possible targets for preventing the disease. The binding of the autoantibody to its relevant antigen on the podocyte cell surface may be sufficient to initiate the disease process. However, much data from experimental and clin­ ical investigations suggest that in situ activation of the complement cascade and generation of the membrane­attack complex of complement in the capillary wall play important roles in the ensuing glomerular permeability defects that lead to pro­ teinuria. This poses a dilemma, since the IgG4 subclass is known to activate complement only poorly, if at all, yet the dominant autoantibodies in the circulation and in the deposits are of the IgG4 subclass.7 Perhaps the concomitant produc­ tion of IgG1 or IgG2 autoantibodies is required for the full expression of the abnormal glomer­ ular permeability. Future investigations will undoubtedly yield answers to these tantalizing questions. Mean­ while, it is likely that the seminal observations of Beck et al. will have a profound effect on how clinicians approach the diagnosis and treatment of membranous nephropathy. Assays for anti­ PLA2R autoantibody (and perhaps anti–neutral endopeptidase as well) may permit the noninva­ sive diagnosis of membranous nephropathy as well as provide a convenient way to follow the activity of the disease in response to treatment. Five decades after its initial recognition, mem­ branous nephropathy is now entering an exciting and dynamic new era.

DOI: 10.1056/NEJMe0904293


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@article{Perkins2009DiabetesCA, title={Diabetes complications and the renin-angiotensin system.}, author={Bruce A Perkins and Lloyd Paul Aiello and Andrzej S. Krolewski}, journal={The New England journal of medicine}, year={2009}, volume={361 1}, pages={83-5} }