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Kidney Week

Abstract: FR-PO338

Modelling APRT Deficiency in Kidney Cells In Vitro

Session Information

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic


  • Helgudottir, Hildur Run, Heilbrigdisvisindasvid - Haskoli Island, Reykjavik, Iceland
  • Palsson, Runolfur, Landspitali–The National University Hospital of Iceland, Reykjavik, Iceland
  • Edvardsson, Vidar O., Landspitali–The National University Hospital of Iceland, Reykjavik, Iceland
  • Gudjonsson, Thorarinn, Heilbrigdisvisindasvid - Haskoli Island, Reykjavik, Iceland

Group or Team Name

  • APRT Deficiency Research Program of the Rare Kidney Stone Consortium

Adenine phosphoribosyltransferase deficiency (APRTd) is a rare autosomal recessive disorder of adenine metabolism that results in the generation and renal excretion of large amounts of the poorly soluble 2,8-dihydroxyadenine (DHA). Affected individuals form urinary stones and crystal nephropathy characterized by inflammation and fibrosis leading to progressive chronic kidney disease. Improved understanding of the mechanisms of DHA crystal-induced kidney injury and identification of alternative therapeutic approaches remain essential unmet needs. The aim of this study was to establish a cell culture model for the characterization of inflammatory and phenotypic changes associated with DHA crystal-induced kidney injury that may be used as targets for clinical interventions.


Two kidney cell lines, Madin-Darby canine cell line (MDCK) and human embryonic cell line (HEK293) were used in the study. Both cell lines were treated with DHA in concentrations similar to those observed in the urine of untreated humans with APRTd, both in monolayers and 3D/transwell assays. Further, siRNA against APRT was utilized to knock down the gene in HEK293. Read-out assay included cell viability, RT-PCR, western blot and immunostaining.


APRT knockdown was successful and confirmed with RT-qPCR. Expression of the APRT gene was significantly reduced, and the morphology of the cells changed with knockdown, cells showing more elongated protrusions than control cells. The addition of DHA did not significantly affect cell viability. Initial analysis demonstrated an increase in the expression of proinflammatory markers (interleukin (IL)-1β and IL-8) in HEK293 cells upon DHA treatment, indicating an inflammatory response.


We have established a cell culture model that captures APRT deficiency in MDCK and HEK293 kidney cell lines. Preliminary data suggest that DHA treatment of these cell lines in vitro induces an inflammatory response. Ongoing experiments focus on further characterizing the inflammatory response pathways and phenotypic changes in the search for disease-specific targets for clinical interventions.


  • Government Support – Non-U.S.