Your browser doesn't support javascript.
loading
Impaired Renal HCO3- Excretion in Cystic Fibrosis.
Berg, Peder; Svendsen, Samuel L; Sorensen, Mads V; Larsen, Casper K; Andersen, Jesper Frank; Jensen-Fangel, Søren; Jeppesen, Majbritt; Schreiber, Rainer; Cabrita, Ines; Kunzelmann, Karl; Leipziger, Jens.
Afiliación
  • Berg P; Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus, Denmark.
  • Svendsen SL; Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus, Denmark.
  • Sorensen MV; Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus, Denmark.
  • Larsen CK; Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus, Denmark.
  • Andersen JF; Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus, Denmark.
  • Jensen-Fangel S; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
  • Jeppesen M; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
  • Schreiber R; Department of Physiology, University of Regensburg, Regensburg, Germany.
  • Cabrita I; Department of Physiology, University of Regensburg, Regensburg, Germany.
  • Kunzelmann K; Department of Physiology, University of Regensburg, Regensburg, Germany.
  • Leipziger J; Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus, Denmark leip@biomed.au.dk.
J Am Soc Nephrol ; 31(8): 1711-1727, 2020 08.
Article en En | MEDLINE | ID: mdl-32703846
BACKGROUND: Patients with cystic fibrosis (CF) do not respond with increased urinary HCO3- excretion after stimulation with secretin and often present with metabolic alkalosis. METHODS: By combining RT-PCR, immunohistochemistry, isolated tubule perfusion, in vitro cell studies, and in vivo studies in different mouse models, we elucidated the mechanism of secretin-induced urinary HCO3- excretion. For CF patients and CF mice, we developed a HCO3- drinking test to assess the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in urinary HCO3-excretion and applied it in the patients before and after treatment with the novel CFTR modulator drug, lumacaftor-ivacaftor. RESULTS: ß-Intercalated cells express basolateral secretin receptors and apical CFTR and pendrin. In vivo application of secretin induced a marked urinary alkalization, an effect absent in mice lacking pendrin or CFTR. In perfused cortical collecting ducts, secretin stimulated pendrin-dependent Cl-/HCO3- exchange. In collecting ducts in CFTR knockout mice, baseline pendrin activity was significantly lower and not responsive to secretin. Notably, patients with CF (F508del/F508del) and CF mice showed a greatly attenuated or absent urinary HCO3--excreting ability. In patients, treatment with the CFTR modulator drug lumacaftor-ivacaftor increased the renal ability to excrete HCO3-. CONCLUSIONS: These results define the mechanism of secretin-induced urinary HCO3- excretion, explain metabolic alkalosis in patients with CF, and suggest feasibility of an in vivo human CF urine test to validate drug efficacy.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bicarbonatos / Fibrosis Quística / Riñón Límite: Animals / Humans / Male Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bicarbonatos / Fibrosis Quística / Riñón Límite: Animals / Humans / Male Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos