Focal segmental glomerulosclerosis; why does it occur segmentally?

  • Michio Nagata
  • Namiko Kobayashi
  • Satoshi Hara
Invited Review


Podocyte loss is the fundamental basis of glomerulosclerosis. Focal segmental glomerulosclerosis (FSGS) is a progressive glomerular disease, and its glomerular features are a prototype of podocyte loss-driven glomerulosclerosis. The glomerular pathology of FSGS is characterized by a focal and segmental location of the sclerotic lesions in human FSGS; segmental sclerosis often shows simultaneous intra- and extra-capillary changes, including parietal cell migration, capillary collapse, hyaline deposition, and intra-capillary thrombi and occasional hypercellularity. This suggests that local cellular events, initiated by podocyte loss, are the basis of the segmental lesions in FSGS. Using podocyte-specific injury by toxin administration, a series of recent works has identified the cellular basis of the glomerular response to podocyte loss. This review discusses the molecular pathway of the local response to podocyte loss and its progression to sclerosis. Recent results suggest that segmental sclerosis is a physiological tissue response aimed at halting protein leakage from a disrupted filtration barrier.


Focal segmental glomerulosclerosis (FSGS) Podocyte loss Parietal cells Microangiopathy Foam cells 



The author celebrates the 80th birthday of Professor W. Kriz and congratulates him for his life work of unique and thought-provoking morphology studies interpreting kidney function and diseases. The content of the present manuscript is based on the recent works from our laboratory supported by the Grants-in-Aid for Scientific Research program of the Japan Society for the Promotion of Science (KAKEN; research project no. 17 K09685 and 26461210) and the Progressive Renal Disease Research program of the Ministry of Health, Labor. The author thanks Professor W. Kriz for understanding and continuous encouragement for my podocyte research since 1989 started at Heidelberg.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Kidney and Vascular Pathology, Faculty of MedicineUniversity of TsukubaTsukuba-CityJapan
  2. 2.NephrologyTokyo Medical and Dental UniversityTokyoJapan
  3. 3.RheumatologyKanazawa University Graduate School of MedicineKanazawaJapan

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