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Abstract: PO1658

Is There a Contribution of Genes Involved in Hereditary Nephropathies to AKI?

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Carriazo, Sol Maria, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Madrid, Spain
  • Sanchez-Nino, Maria Dolores, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Madrid, Spain
  • Castañeda Infante, Laura J., Hospital Universitario Fundacion Jimenez Diaz, Madrid, Madrid, Spain
  • Ortiz, Alberto, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Madrid, Spain
Background

The diagnosis of hereditary kidney disease has been improving with the use of novel diagnostic tools in the last decades. More than 600
genes have been detected using techniques such as whole exome sequencing. However, it is not clear if those genes causing hereditary nephropaties have any independent contribution in the pathogenesis of acquired nephropaties.

Methods

We analyzed the kidney transcriptomic after 24 hours of acute kidney injury (AKI) induced by folic acid in a murine model. In this database we evaluated if 625 genes described as responsible for hereditary nephropathies were expressed significantly. Later, using transcriptomic databeses of human nephropathies (Nephroseq), we evaluated the correlation between those differentially expressed genes and glomerular filtration. Using the software Gorilla, a functional enrichment analysis was done. Some of those were validated in our laboratory using RT-PCR.

Results

Among 25051 genes, 7443 (29.7%) were found to have a significant modification in their expression in AKI (p<0.05). When analyzing 625 responsible for familiar nephropaties, we identified 615 in our database. 260 (41,6%) of those genes were differentially expressed in our model. An association between 241 of those 260 differentially expressed genes and glomerular filtration rate in human nephropaties was identified. The most enriched GO process were "complement activation", "protein activation cascade", "activation of immune response" and "RNA processing". 7 of the 241 mentioned genes , showed changes greater than twofold. On the other hand, 18 of the 241 showed more than a half-fold change.
We have validated the expression of 2 of the genes in acute kidney injury (SLC34A3, FN1), which supports the relevance of the transcriptomic results.

Conclusion

Several genes responsible for familiar nephropathies are differentially expressed in acquired nephropathies, suggesting that they could play a role in its pathogenesis, through complement activation, protein activation of immune response and the regulation of the RNA processing. The identification of those genes showing a more significant change will allow us to select candidates for further studies and new possible therapeutic targets in kidney damage.

Funding

  • Clinical Revenue Support