Elexacaftor/tezacaftor/ivacaftor corrects salt-wasting in cystic fibrosis

Abstract

Background: People with cystic fibrosis (pwCF) are at increased risk for fluid and electrolyte imbalances due to continuous salt loss. Congruently, guidelines advocate increased salt intake. However, pwCF are also at increased risk for developing cardiovascular disease. Understanding how CFTR modulators affect fluid and electrolyte homeostasis is important to provide evidence-based guidance for pwCF treated with CFTR modulators.

Methods: We quantified the effect of Elexacaftor/tezacaftor/ivacaftor (ETI) treatment on blood pressure, electrolyte- and acid-base balance, aldosterone levels, and the diuretic and natriuretic response to an oral NaHCO₃ and volume loading test in 50 pwCF initiating ETI treatment.

Results: In pwCF, ETI treatment increased blood pressure, plasma Na⁺, and the diuretic response to oral NaHCO₃ and volume loading. Congruently, ETI markedly decreased heart rate, aldosterone levels, venous total CO₂ and the proportion of pwCF with low plasma Na⁺.

Conclusions: In pwCF, ETI treatment improves NaCl and fluid conservation. Future guidelines should consider an increased risk for cardiovascular disease in pwCF after initiation of CFTR modulator treatment. Salt repletion appears unnecessary in ETI-treated pwCF.

Keywords: Blood pressure; Cystic fibrosis; Elexacaftor/tezacaftor/ivacaftor; Pseudobartter.