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Abstract: TH-OR075

The Cystic Fibrosis Urine Test

Session Information

Category: Fluid and Electrolytes

  • 902 Fluid and Electrolytes: Clinical

Authors

  • Berg, Peder, Aarhus University, Aarhus C, Denmark
  • Svendsen, Samuel L.C., Aarhus University, Aarhus C, Denmark
  • Sorensen, Mads Vaarby, Aarhus University, Aarhus C, Denmark
  • Jensen-Fangel, Soren, Aarhus University Hospital, Aarhus N, Denmark
  • Jeppesen, Majbritt, Aarhus University Hospital, Aarhus N, Denmark
  • Kunzelmann, Karl, University of Regensburg, Regensburg, Germany
  • Leipziger, Jens G., Aarhus University, Aarhus C, Denmark
Background

Cystic fibrosis (CF) patients commonly present with systemic electrolyte abnormalities and metabolic alkalosis, likely caused by renal dysfunction of base excretion. In mouse studies, we have identified the physiological mechanism of CFTR-dependent urine bicarbonate excretion in the collecting duct, which depends on functional pendrin and CFTR in β-intercalated cells. Remarkably, CFTR and pendrin knock-out mice cannot respond to increase their urine bicarbonate excretion during the first 3 hours following a defined acute gastric load.

Methods

We have developed a human, non-invasive CF urine test that is simple and quantifies the ability to excrete bicarbonate with the urine after oral intake of 79 mg/ kg BW NaHCO3.

Results

In human CF patients (homozygote for ΔF508, n=6), we can show a reduced ability (~ 40% as compared to normal) to excrete urinary bicarbonate after application of this CF urine test. We hypothesized that the CF urine test can verify and quantify therapy success in CF patients treated with the novel CF modulator drug Orkambi®. Currently, 6 CF patients have been studied before and after 4 weeks of treatment with Orkambi®. The results showed an appr. 2-fold increase of the urinary [HCO3-] in the treated CF group.

Conclusion

These results indicate that CFTR knock-out mice and human CF patients present with the inability/reduced ability to excrete a defined oral HCO3- load. Furthermore, the CF modulator drug Orkambi® can partially normalize the challenged urinary HCO3- excretion in CF patients.

Funding

  • Government Support - Non-U.S.