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      Pathophysiological advances in membranous nephropathy: time for a shift in patient's care.

      1 , 2

      Lancet (London, England)

      Elsevier BV

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          Abstract

          Membranous nephropathy is a major cause of nephrotic syndrome of non-diabetic origin in adults. It is the second or third leading cause of end-stage renal disease in patients with primary glomerulonephritis, and is the leading glomerulopathy that recurs after kidney transplantation (occurring in about 40% of patients). Treatment with costly and potentially toxic drugs remains controversial and challenging, partly because of insufficient insight into the pathogenesis of the disease and absence of sensitive biomarkers of disease activity. The disease is caused by the formation of immune deposits on the outer aspect of the glomerular basement membrane, which contain podocyte or planted antigens and circulating antibodies specific to those antigens, resulting in complement activation. In 2002, podocyte neutral endopeptidase was identified as an antigenic target of circulating antibodies in alloimmune neonatal nephropathy, and in 2009, podocyte phospholipase A2 receptor (PLA2R) was reported as an antigenic target in autoimmune adult membranous nephropathy. These major breakthroughs were translated to clinical practice very quickly. Measurement of anti-PLA2R antibodies in serum and detection of PLA2R antigen in glomerular deposits can now be done routinely. Anti-PLA2R antibodies have high specificity (close to 100%), sensitivity (70-80%), and predictive value. PLA2R detection in immune deposits allows for retrospective diagnosis of PLA2R-related membranous nephropathy in archival kidney biopsies. These tests already have a major effect on diagnosis and monitoring of treatment, including after transplantation.

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          Author and article information

          Journal
          Lancet
          Lancet (London, England)
          Elsevier BV
          1474-547X
          0140-6736
          May 16 2015
          : 385
          : 9981
          Affiliations
          [1 ] Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155, Paris, France; INSERM, UMR_S 1155, Paris, France; AP-HP, Department of Nephrology and Dialysis, Hôpital Tenon, Paris, France. Electronic address: pierreronco@yahoo.fr.
          [2 ] Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155, Paris, France; INSERM, UMR_S 1155, Paris, France.
          Article
          S0140-6736(15)60731-0
          10.1016/S0140-6736(15)60731-0
          26090644

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