Kidney effects of triple CFTR modulator therapy in people with cystic fibrosis

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) is a novel modulator of the cystic fibrosis transmembrane conductance regulator (CFTR) that has significantly improved the respiratory outcomes of people with cystic fibrosis (pwCF). However, its effects on other organs, such as the kidneys—where CFTR is also expressed—remain unclear. Since pwCF are at risk for both kidney disease and urolithiasis, this study aimed to explore ETI’s potential influence on renal function, volume regulation, and urolithiasis risk factors.

Methods: This prospective, observational, single-center, before-and-after cohort study included adult pwCF eligible for ETI. Plasma and urinary profiles were analyzed to evaluate changes in renal function (using the 2021 CKD-EPIcreatinine and CKD-EPIcreatinine-cystatin C equations), volume status (assessed via aldosterone/renin ratio and blood pressure), and urolithiasis risk factors. Measurements were taken at the initiation of ETI (M0) and seven months later (M7).

Results: Nineteen pwCF were enrolled. No significant change in renal function was detected between M0 and M7 (2021 CKD-EPIcreatinine: 105.5 ml/min/1.73 m² at M0 vs. 103.3 ml/min/1.73 m² at M7; P = .17). A significant reduction was observed in aldosterone levels (370.3 pmol/L at M0 vs. 232.4 pmol/L at M7; P = .02) and the aldosterone/renin ratio (33.6 at M0 vs. 21.8 at M7; P = .03). Additionally, a significant decrease in urinary magnesium excretion (magnesuria) was noted (4.6 mmol/day at M0 vs. 3.8 mmol/day at M7; P = .01).

Conclusion: These results suggest that ETI does not affect renal function in the short term among adult pwCF and may help correct VX-445 secondary hyperaldosteronism associated with excessive sweat losses. Further studies are needed to explore the clinical implications of reduced magnesuria under ETI treatment, particularly its impact on the risk of developing urolithiasis.