12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Understanding podocytopathy and its relevance to clinical nephrology

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Podocytopathies are the most common group of glomerular disorder leading to proteinuria. On the basis of pathophysiology, light microscopic and ultrastructural evaluation, the podocytopathies include minimal change disease, diffuse mesangial sclerosis, focal segmental glomerulosclerosis and collapsing glomerulopathy. The present review summarizes the basic etiopathogenesis of podocytopthies, highlights the common genetic and acquired factors in its causation, puts forth various diagnostic modalities and discusses the role of emerging agents or treatment.

          Related collections

          Most cited references49

          • Record: found
          • Abstract: found
          • Article: not found

          NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome.

          Familial idiopathic nephrotic syndromes represent a heterogeneous group of kidney disorders, and include autosomal recessive steroid-resistant nephrotic syndrome, which is characterized by early childhood onset of proteinuria, rapid progression to end-stage renal disease and focal segmental glomerulosclerosis. A causative gene for this disease, NPHS2, was mapped to 1q25-31 and we report here its identification by positional cloning. NPHS2 is almost exclusively expressed in the podocytes of fetal and mature kidney glomeruli, and encodes a new integral membrane protein, podocin, belonging to the stomatin protein family. We found ten different NPHS2 mutations, comprising nonsense, frameshift and missense mutations, to segregate with the disease, demonstrating a crucial role for podocin in the function of the glomerular filtration barrier.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis.

            Focal and segmental glomerulosclerosis (FSGS) is a common, non-specific renal lesion. Although it is often secondary to other disorders, including HIV infection, obesity, hypertension and diabetes, FSGS also appears as an isolated, idiopathic condition. FSGS is characterized by increased urinary protein excretion and decreasing kidney function. Often, renal insufficiency in affected patients progresses to end-stage renal failure, a highly morbid state requiring either dialysis therapy or kidney transplantation. Here we present evidence implicating mutations in the gene encoding alpha-actinin-4 (ACTN4; ref. 2), an actin-filament crosslinking protein, as the cause of disease in three families with an autosomal dominant form of FSGS. In vitro, mutant alpha-actinin-4 binds filamentous actin (F-actin) more strongly than does wild-type alpha-actinin-4. Regulation of the actin cytoskeleton of glomerular podocytes may be altered in this group of patients. Our results have implications for understanding the role of the cytoskeleton in the pathophysiology of kidney disease and may lead to a better understanding of the genetic basis of susceptibility to kidney damage.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function.

              Progressive kidney failure is a genetically and clinically heterogeneous group of disorders. Podocyte foot processes and the interposed glomerular slit diaphragm are essential components of the permeability barrier in the kidney. Mutations in genes encoding structural proteins of the podocyte lead to the development of proteinuria, resulting in progressive kidney failure and focal segmental glomerulosclerosis. Here, we show that the canonical transient receptor potential 6 (TRPC6) ion channel is expressed in podocytes and is a component of the glomerular slit diaphragm. We identified five families with autosomal dominant focal segmental glomerulosclerosis in which disease segregated with mutations in the gene TRPC6 on chromosome 11q. Two of the TRPC6 mutants had increased current amplitudes. These data show that TRPC6 channel activity at the slit diaphragm is essential for proper regulation of podocyte structure and function.
                Bookmark

                Author and article information

                Journal
                Indian J Nephrol
                Indian J Nephrol
                IJN
                Indian Journal of Nephrology
                Medknow Publications & Media Pvt Ltd (India )
                0971-4065
                1998-3662
                Jan-Feb 2015
                : 25
                : 1
                : 1-7
                Affiliations
                [1]Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
                Author notes
                Address for correspondence: Dr. Amit K. Dinda, Department of Pathology, All India Institute of Medical Sciences, New Delhi, India. E-mail: dindaaiims@ 123456gmail.com
                Article
                IJN-25-1
                10.4103/0971-4065.134531
                4323905
                bff927e0-ba4e-46ef-852f-c1e2ea3f9022
                Copyright: © Indian Journal of Nephrology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Review Article

                Nephrology
                collapsing glomerulopathy,diffuse mesangial sclerosis,focal segmental glomerulosclerosis,minimal change disease,podocytopathy,proteinuria

                Comments

                Comment on this article