Abstract: TH-PO572

Effectiveness of MTT in Liver Phenotype in a Model of Autosomal Recessive Polycystic Kidney Disease (ARPKD)

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
  • Lamas-Gonzalez, Olaya, Health Research Institute of Santiago de Compostela (IDIS)., Santiago de Compostela, CNR, Spain
  • Barcia de la Iglesia, Ana, Instituto de Investigacion Sanitaria (IDIS) de Santiago de Compostela, Santiago de Compostela, Spain
  • Bañales, Jesus, Biodonostia Health Research Institute, San Sebastián, Spain
  • Diaz-Rodriguez, Candido, University Clinical Hospital of Santiago de Compostela (CHUS), Santiago de Compostela, Spain
  • Garcia-Gonzalez, Miguel A., Health Research Institute of Santiago de Compostela (IDIS)., Santiago de Compostela, CNR, Spain
Background

Polycystic liver disease (PLD) are genetic disorders characterized by progressive bile duct dilatation and cyst development in hepatic parenchyma. PLD are inherited in a dominant or recessive form and can develop alone or in association with polycystic kidney disease (PKD). A number of different mechanisms have been related to the pathogenesis of Polycystic Disease, which we focused on alteration in the extracellular matrix (ECM). MTT is a Metalloproteinases inhibitor. In previous work (ASN2016), we have shown the effectiveness of MTT in models of Autosomal Dominant PKD (ADPKD), both in renal and hepatic phenotype.

Methods

Here, we focused our work testing MTT as a potential therapy for PLD associated to Autosomal Recessive PKD (ARPKD). In this regard, we use a model of ARPKD, Pkhd1del3-4/del3-4 (Pkhd1-KO), to test the effectiveness of MTT in hepatic cystogenesis.

Results

In our previous work, we showed the benefit effect of MTT in Autosomal Dominant Polycystic Kidney Disease (ADPKD) inhibiting the hepatic cystogeneis and collecting duct cyst (DBA+ cyst). Now, we have deeply characterized the liver phenotype in our ARPKD model, identifying a time depending gender effect of disease progression. We have also tested MTT, alone and in combination with Tolvaptan, in different points resulting in a significant inhibition of hepatic cystic progression in ARPKD.

Conclusion

In ASN 2016, our group showed the effect of MTT in Autosomal Dominant Polycystic Kidney Disease (ADPKD) inhibiting the hepatic cystogeneis and collecting duct cyst (DBA+ cyst). With this work, we have demonstrated the effectiveness of MTT in the inhibition of hepatic phenotype of ARPKD.