Impact of renin-angiotensin system inhibitors discontinuation in advanced chronic kidney disease: a target trial emulation
Abstract
Background Renin-angiotensin system (RAS) inhibitors are a cornerstone of cardiovascular and kidney risk modification in chronic kidney disease (CKD). Yet, they are often discontinued in advanced CKD to limit adverse effects or to delay kidney replacement therapy (KRT). Methods From the CKD-Renal Epidemiology and Information Network prospective cohort study, we selected participants with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 and treated with RAS inhibitors. We performed a target trial emulation with parametric g-formula to compare two strategies: to discontinue or to continue RAS inhibitors. Models were adjusted for sociodemographics, clinical and laboratory characteristics, and drug prescriptions. Outcomes were the composite of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure, i.e. major cardiovascular events (MACE), and KRT initiation. Results Among the 1 434 patients included (median age 68 years, median eGFR 25 mL/min/1.73m2, 35% women), 386 (27%) discontinued RAS inhibitors over a median follow-up of 35 months. Very few events related to adverse drug reactions were reported in the 3 months preceding RAS inhibitor discontinuation (n = 23), but their incidence over this period was ∼13-fold higher than that during the entire follow-up. The 3-year adjusted relative risk of MACE associated to discontinuing RAS inhibitors, compared to continuing, was 2.02 (95% CI, 1.62 to 2.47), and that of KRT initiation, 1.34 (95% CI, 1.14 to 1.60). Discussion RAS inhibitor discontinuation was strongly associated with MACE and KRT risks, major causes of morbidity and mortality in advanced CKD. Our findings, consistent with prior data, suggest the risk-benefit balance favors continued use with close monitoring.
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BibTeX
@article{maisons2026impact,
title = {{Impact of renin-angiotensin system inhibitors discontinuation in advanced chronic kidney disease: a target trial emulation}},
author = {Valentin Maisons and Margaux Costes-Albrespic and Sophie Liabeuf and Solène Laville and Ziad Massy and Angelo Karaboyas and Roberto Pecoits-Filho and Emilie Moutard and Marie Metzger and Jean-Michel Halimi and Etienne Dantan and Natalia Alencar de Pinho and Bénédicte Sautenet},
journal = {Clinical Kidney Journal},
year = {2026},
month = sep,
doi = {10.1093/ckj/sfag304},
url = {https://u-picardie.hal.science/hal-05740728v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Impact of renin-angiotensin system inhibitors discontinuation in advanced chronic kidney disease: a target trial emulation
AU - Valentin Maisons
AU - Margaux Costes-Albrespic
AU - Sophie Liabeuf
AU - Solène Laville
AU - Ziad Massy
AU - Angelo Karaboyas
AU - Roberto Pecoits-Filho
AU - Emilie Moutard
AU - Marie Metzger
AU - Jean-Michel Halimi
AU - Etienne Dantan
AU - Natalia Alencar de Pinho
AU - Bénédicte Sautenet
PY - 2026
DA - 2026/09/04
JO - Clinical Kidney Journal
DO - 10.1093/ckj/sfag304
UR - https://u-picardie.hal.science/hal-05740728v1
AB - Background Renin-angiotensin system (RAS) inhibitors are a cornerstone of cardiovascular and kidney risk modification in chronic kidney disease (CKD). Yet, they are often discontinued in advanced CKD to limit adverse effects or to delay kidney replacement therapy (KRT). Methods From the CKD-Renal Epidemiology and Information Network prospective cohort study, we selected participants with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 and treated with RAS inhibitors. We performed a target trial emulation with parametric g-formula to compare two strategies: to discontinue or to continue RAS inhibitors. Models were adjusted for sociodemographics, clinical and laboratory characteristics, and drug prescriptions. Outcomes were the composite of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure, i.e. major cardiovascular events (MACE), and KRT initiation. Results Among the 1 434 patients included (median age 68 years, median eGFR 25 mL/min/1.73m2, 35% women), 386 (27%) discontinued RAS inhibitors over a median follow-up of 35 months. Very few events related to adverse drug reactions were reported in the 3 months preceding RAS inhibitor discontinuation (n = 23), but their incidence over this period was ∼13-fold higher than that during the entire follow-up. The 3-year adjusted relative risk of MACE associated to discontinuing RAS inhibitors, compared to continuing, was 2.02 (95% CI, 1.62 to 2.47), and that of KRT initiation, 1.34 (95% CI, 1.14 to 1.60). Discussion RAS inhibitor discontinuation was strongly associated with MACE and KRT risks, major causes of morbidity and mortality in advanced CKD. Our findings, consistent with prior data, suggest the risk-benefit balance favors continued use with close monitoring.
SN - 2048-8505
SN - 2048-8513
ER -