ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2022 and some content may be unavailable. To unlock all content for 2022, please visit the archives.

Abstract: FR-PO256

Single Gene Mutations in Pkd1 or Tsc2 Alter Extracellular Vesicles Production and Trafficking

Session Information

Category: Genetic Diseases of the Kidneys

  • 1101 Genetic Diseases of the Kidneys: Cystic


  • Bissler, John J., St. Jude Children's Research Hospital, Memphis, Tennessee, United States
  • Kumar, Prashant, US FDA National Center for Toxicological Research, Little Rock, Arkansas, United States
  • Al-Zadjali, Fahad, Sultan Qaboos University, Muscat, Oman
  • Yao, Ying, The University of Tennessee Health Science Center College of Medicine, Memphis, Tennessee, United States
  • Hofherr, Alexis, Albert-Ludwigs-Universitat Freiburg, Freiburg im Breisgau, Baden-Württemberg, Germany
  • Kottgen, Michael, Albert-Ludwigs-Universitat Freiburg, Freiburg im Breisgau, Germany
  • Mehta, Darshan, US FDA National Center for Toxicological Research, Little Rock, Arkansas, United States
  • Gross, Kenneth W., Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States

Patients with autosomal dominant polycystic kidney disease (ADPKD) and the cystic disease associated with tuberous sclerosis complex (TSC) are born with normal or near normal kidneys that later develop cysts and prematurely lose function. Both renal cystic diseases appear to be mediated, at least in part, by disease promoting extracellular vesicles (EVs) that can induce genetically intact cells to participate in the renal disease process.


We used centrifugation and size exclusion chomotography to isolate the EVs for study. We characterized the EVs using tunable resistive pulse sensing, dynamic light scattering, transmission electron microscopy and western blot analysis. We performed EV trafficking studies using a dye approach in both tissue culture and in vivo studies.


We have previously reported that loss of the Tsc2 gene significantly increased EV production and here demonstrate that the loss of the Pkd1 gene also significantly increases EV production. Using a cell culture system, we also show that loss of either the Tsc2 or Pkd1 gene results in EVs that exhibit an enhanced uptake by renal epithelial cells and a prolonged half-life, possibly further accentuating the EV dose effect. Loss of the primary cilia significantly reduces EV production in renal collecting duct cells. We document that EVs from cells that have loss of polycystin-1 have greatly altered kinetics and a profound effect on the EV half-life, possibly impacting the duration of EV cargo effect on the recipient cell.


These results demonstrate the interplay between primary cilia and EVs and support a role for EVs in polycystic kidney disease pathogenesis.


  • Private Foundation Support