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Therapeutic trials in adult FSGS: lessons learned and the road forward

Nature Reviews Nephrology volume 17, pages 619–630 (2021)Cite this article

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Abstract

Focal segmental glomerulosclerosis (FSGS) is not a specific disease entity but a lesion that primarily targets the podocyte. In a broad sense, the causes of the lesion can be divided into those triggered by a presumed circulating permeability factor, those that occur secondary to a process that might originate outside the kidneys, those caused by a genetic mutation in a podocyte or glomerular basement membrane protein, and those that arise through an as yet unidentifiable process, seemingly unrelated to a circulating permeability factor. A careful attempt to correctly stratify patients with FSGS based on their clinical presentation and pathological findings on kidney biopsy is essential for sound treatment decisions in individual patients. However, it is also essential for the rational design of therapeutic trials in FSGS. Greater recognition of the pathophysiology underlying podocyte stress and damage in FSGS will increase the likelihood that the cause of an FSGS lesion is properly identified and enable stratification of patients in future interventional trials. Such efforts will facilitate the identification of effective therapeutic agents.

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Fig. 1: Podocyte structural changes in FSGS.
Fig. 2: Foot process effacement in FSGS.
Fig. 3: Ultrastructural visualization of foot process effacement.
Fig. 4: FSGS findings by light microscopy.
Fig. 5: Electron microscopy evaluation of FSGS.

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Authors and Affiliations

  1. Division of Nephrology and Infectious Diseases, AZ Sint-Jan Brugge, Brugge, Belgium

    An S. De Vriese

  2. Department of Internal Medicine, Ghent University, Ghent, Belgium

    An S. De Vriese

  3. Department of Nephrology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands

    Jack F. Wetzels

  4. Department of Medicine, Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Richard J. Glassock

  5. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Sanjeev Sethi

  6. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA

    Fernando C. Fervenza

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A.S.D.V and F.C.F. wrote the article. All authors researched data for the article, contributed substantially to discussion of the content and reviewed and/or edited the manuscript before submission.

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De Vriese, A.S., Wetzels, J.F., Glassock, R.J. et al. Therapeutic trials in adult FSGS: lessons learned and the road forward. Nat Rev Nephrol 17, 619–630 (2021). https://doi.org/10.1038/s41581-021-00427-1

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