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Kidney Week

Abstract: TH-PO573

Cytokine TWEAK Promotes Cystogenesis in Autosomal Dominant Polycystic Kidney Disease (ADPKD) in a Time Dependent Manner

Session Information

Category: Genetic Diseases of the Kidney

  • 801 Cystic Kidney Diseases

Authors

  • Cordido, Adrian, Instituto de Investigacion Sanitaria (IDIS) de Santiago de Compostela, Santiago de Compostela, Spain
  • Sanz, Ana Belen, Instituto de Investigacion Sanitaria Fundacion Jimenez Diaz, Madrid, Spain
  • Barcia de la Iglesia, Ana, Instituto de Investigacion Sanitaria (IDIS) de Santiago de Compostela, Santiago de Compostela, Spain
  • Diaz-Rodriguez, Candido, University Clinical Hospital of Santiago de Compostela (CHUS), Santiago de Compostela, Spain
  • Ortiz, Alberto, Fundacion Jimenez Diaz, Madrid, Spain
  • Garcia-Gonzalez, Miguel A., Instituto de Investigacion Sanitaria (IDIS) de Santiago de Compostela, Santiago de Compostela, Spain
Background

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common monogenic disorder in which kidneys develop fluid-filled cyst derived from the tubule epithelial cells. Several mechanisms are associated with cyst initiation and cyst progression, recent findings aim inflammation as one the most important molecular mechanism in the progression of ADPKD.
TWEAK (tumor necrosis factor TNF-like weak inducer of apoptosis) is a TNF-like cytokine and member of the TNF superfamily. TWEAK promotes inflammation, proliferation, cell death and angiogenesis. However, the role of TWEAK in ADPKD is unknown.

Methods

We have studied the effect of TWEAK in our ADPKD animal model, Pkd1cko/ckoTam-Cre. This model presents a cystogenesis developmental switch, because the inactivation of Pkd1 gene in different points of life determines cystic phenotype.

Results

We tested TWEAK in different developmental windows of our animal model (Pkd1cko/ckoTam-Cre) we show that proinflammatory cytokines can be accelerates the progression of ADPKD. The mice that received TWEAK presented higher levels of BUN and worst survival rate than the group of control mice.
In addition, TWEAK promotes the progression of hepatic cystic phenotype (PLD associated to ADPKD). These results suggest that TWEAK not online acts at the kidney level.

Conclusion

Doing use of Pkd1cko/ckoTam-Cre animal model, we demonstrated that TWEAK promotes the progression of ADPKD in a time dependent manner. We results show how inflammation may modulate the severity of ADPKD and the possibility of a treatment with anti-inflammatory therapy.