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

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) is a new cystic fibrosis transmembrane conductance regulator (CFTR) modulator that has transformed the respiratory prognosis of people with cystic fibrosis (pwCF). However, its impact on other organs such as the kidneys, where CFTR is expressed, remains unclear. Since pwCF are risk of both kidney disease and urolithiasis, we aimed to study the potential effects of ETI on renal function, volume status, and risk factors for urolithiasis.
Methods: This prospective, observational, single-center, before-after cohort study, involved adult pwCF eligible for ETI. The changes in plasma and urinary profiles were assessed by comparing renal function (using 2021 CKD-EPI _creatinine and 2021 CKD-EPI _{creatinine-cystatin C} formulas), volume status (using aldosterone/renin ratio and blood pressure), and risk factors for urolithiasis, at the time of ETI introduction (M0) and 7 months after (M7).
Results: Nineteen pwCF were included. No significant change in renal function was observed between M0 and M7 (2021 CKD-EPI _creatinine : 105.5 ml/min/1.73 m² at M0 vs. 103.3 ml/min/1.73 m² at M7; P  = .17). There was a significant reduction in aldosterone level (370.3 pmol/l at M0 vs. 232.4 pmol/l at M7; P  = .02) and aldosterone/renin ratio (33.6 at M0 vs. 21.8 at M7; P  = .03). Among the risk factors for urolithiasis, a significant reduction in magnesuria level was found (4.6 mmol/d at M0 vs. 3.8 mmol/d at M7; P  = .01).
Conclusion: These findings suggest that ETI seem to have no short-term impact on the renal function of adult pwCF and appears to correct secondary hyperaldosteronism due to excessive sweat losses. Further investigations are needed to determine the potential impact of decreased magnesuria observed under ETI therapy on the risk of urolithiasis.
Competing Interests: D.F. has received speaker fees or travel support from AstraZeneca, Astellas, Lilly and Fresenius Kabi. I.D. declares an activity as a clinical trial investigator for Vertex and acknowledges having received support for conference travel from Viatris. L.K. having received grants from Fresenius Kabi, Nestlé, Lallemand, AstraZeneca and consultancy or speaker fees or travel support from AstraZeneca, Lilly, Baxter, Bayer, and Fresenius Kabi. P.G., E.N.-C., Q.R., R.N.-J., and S.P. declare no conflicts of interest.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)