Renin-angiotensin system inhibitors and arterial stiffness in chronic kidney disease: results from the chronic renal insufficiency cohort

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Chronic kidney disease (CKD) (n=1201). Intervention: Renin-angiotensin system inhibitors (RASIs) vs. Non-RASI antihypertensive medications (diuretic, beta-blocker, calcium channel blocker, vasodilator, or alpha2-agonist). Primary outcome: Adjusted yearly change in carotid-femoral pulse wave velocity (cfPWV, m/s per year) (p=0.61).

Q: What does this research mean for the field?

Renin-angiotensin system inhibitors do not reduce the longitudinal progression of arterial stiffness compared to non-RASI antihypertensive medications in patients with chronic kidney disease. Novelty: ClaimNovelty.CONTRADICTORY. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

Rachel Shulman; Debbie L. Cohen; Ray R. Townsend; Jordana B. Cohen; the CRIC Study Investigators; Laura M. Dember; Amanda Hyre Anderson; Lawrence J. Appel; Mahboob Rahman; Panduranga S. Rao; James Phillip Lash; Jing Chen; Lotuce Lee Hamm; Alan S. Go; Debbie L. Cohen

doi:10.1038/s41371-026-01241-7

October 31, 2026Journal of Human HypertensionOpen Access

Renin-angiotensin system inhibitors and arterial stiffness in chronic kidney disease: results from the chronic renal insufficiency cohort

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Key result

RAS inhibitors fail to slow arterial stiffness progression compared to other antihypertensives in CKD.

P=0.61
n=1,201

Why the study?

Chronic kidney disease is associated with accelerated arterial stiffness, but evidence on whether renin-angiotensin system inhibitors prevent arterial stiffness is conflicting.

Does a renin-angiotensin system inhibitor (RASI)-based antihypertensive regimen reduce the yearly progression of arterial stiffness (carotid-femoral pulse wave velocity) compared to non-RASI antihypertensive regimens in adults with chronic kidney disease?

Key Points

To determine whether renin-angiotensin system inhibitors (RASIs) prevent longitudinal arterial stiffening compared to non-RASI antihypertensive therapies in patients with chronic kidney disease.
Analyzed 1 201 participants from the Chronic Renal Insufficiency Cohort (CRIC) Study (982 taking RASIs and 219 taking non-RASI agents) followed for a median of 2 years.
Used linear mixed-effects models to assess yearly changes in carotid-femoral pulse wave velocity (cfPWV) and systolic blood pressure in the full cohort and in a monotherapy subset (N = 283).
In the adjusted full cohort, the yearly increase in cfPWV was 0.19 m/s per year (95% CI 0.14 to 0.25) for RASI users versus 0.15 m/s per year (95% CI 0.00 to 0.30) for non-RASI users (p = 0.61).
Among monotherapy users, adjusted yearly cfPWV changes did not differ significantly between RASI (0.11 m/s per year, 95% CI 0.02 to 0.21) and non-RASI regimens (0.03 m/s per year, 95% CI −0.14 to 0.20; p = 0.41).
No significant difference in systolic blood pressure progression over time occurred between RASI and non-RASI users in either the full cohort (adjusted p = 0.36) or the monotherapy cohort (adjusted p = 0.24).

Study Design

Type

Cohort (n=1,201)

Multicenter

Yes

Structured PICO

Does a renin-angiotensin system inhibitor (RASI)-based antihypertensive regimen reduce the yearly progression of arterial stiffness (carotid-femoral pulse wave velocity) compared to non-RASI antihypertensive regimens in adults with chronic kidney disease?

P

Population

1,201 adults with chronic kidney disease (mean age 60 years, 43% female, mean eGFR 46 mL/min/1.73 m2) taking antihypertensive medications with at least two pulse wave velocity measurements, followed for a median of 2 years.

E

Exposure

Participant-reported use of a renin-angiotensin system inhibitor (RASI)-based antihypertensive regimen at the index study visit (n=982 in full cohort; n=203 in monotherapy cohort)

C

Comparator

Participant-reported use of a non-RASI-based antihypertensive regimen (i.e., thiazide, loop, or potassium-sparing diuretic, beta-blocker, calcium channel blocker, vasodilator, or alpha2-agonist) at the index study visit (n=219 in full cohort; n=68 in monotherapy cohort)

O

Outcome

Yearly change in carotid-femoral pulse wave velocity (cfPWV, m/s per year), measured via supine arterial tonometry at up to five annual visits over a median follow-up of 2 yearssurrogate

Main Result

Absolute Event Rate: 0.19% vs 0.15%

p-value: p=0.61

Longitudinal use of renin-angiotensin system inhibitors is not associated with a slower progression of large artery stiffness compared to other antihypertensive classes in patients with chronic kidney disease, suggesting non-RAS mechanisms drive long-term vascular stiffening in this population.

Limitations

Could not determine medication dose, prior duration of use, or adherence.
Potential confounding by indication, as RASIs are often prescribed for proteinuria in CKD.
Adjusted for proteinuria rather than albuminuria, which is a more sensitive marker of kidney damage.
Restricted the cohort to individuals with at least two cfPWV measurements, which may introduce selection bias.
Wide range of CKD severity with substantial inclusion of less severe CKD (average eGFR 46 mL/min/1.73 m2) and unequal distribution across strata limiting power to detect effect modification.
Regional PWV measurements (e.g., femoral-ankle PWV) were not assessed to differentiate central vs. peripheral stiffness.
Censoring individuals at the time of discontinuation or initiation of RASI could introduce bias.
Inability to determine medication dose, prior duration of use, or adherence to medications, with potential for confounding by indication
Adjusted for proteinuria rather than albuminuria, which is a more sensitive marker of kidney damage
Restricted the cohort to individuals with at least two cfPWV measurements, introducing potential selection bias
Unequal distribution across CKD severity strata (219 vs. 918 participants) may have limited statistical power to detect effect modification, and regional PWV was not assessed
Censoring individuals at the time of discontinuation or initiation of RASI could introduce informative censoring bias

Implication

No support for RASI preference to slow stiffness in CKD; leaves open non-RAS mechanisms and should not yet change practice.

Abstract

Chronic kidney disease (CKD) is associated with accelerated arterial stiffness, which contributes to its high burden cardiovascular disease. There is conflicting evidence on whether renin-angiotensin system inhibitors (RASIs) prevent arterial stiffness. We investigated the association between RASIs versus non-RASI antihypertensive medications and yearly changes in carotid-femoral pulse wave velocity (cfPWV) – a measure of arterial stiffness –using a linear mixed-effects model among participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. As a secondary analysis, we restricted the cohort to participants on one antihypertensive medication at baseline. Lastly, we used a linear mixed-effects model to evaluate the relationship between RASI use and systolic blood pressure over time. Of the 1 201 participants who met inclusion criteria, 982 were on RASI and 219 were on a non-RASI medication. Individuals on RASI had a non-significant increase in cfPWV (adjusted cfPWV 0.19 m/s per year, 95% CI 0.14 to 0.25) compared to non-RASI users (adjusted cfPWV 0.15 m/s per year, 95% CI 0.00 to 0.30; p = 0.61). In the monotherapy cohort (N = 283), there was no difference in adjusted yearly change in cfPWV between RASI (0.11 m/s per year, 95% CI 0.02 to 0.21) and non-RASI users (0.03 m/s per year, 95% CI −0.14 to 0.20; p = 0.41). In both cohorts, there was no significant difference in systolic blood pressure over time between RASI and non-RASI users. Future research to mitigate the accelerated large artery stiffness in patients with CKD should focus on targetable mechanisms beyond the renin-angiotensin system.

Discussion

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Cite This Study

Shulman et al. (2026) conducted a cohort in Chronic kidney disease (CKD) (n=1,201). Renin-angiotensin system inhibitors (RASIs) vs. Non-RASI antihypertensive medications (diuretic, beta-blocker, calcium channel blocker, vasodilator, or alpha2-agonist) was evaluated on Adjusted yearly change in carotid-femoral pulse wave velocity (cfPWV, m/s per year) (p=0.61). Renin-angiotensin system inhibitors did not significantly alter yearly arterial stiffness progression (cfPWV 0.19 vs 0.15 m/s/year; p=0.61) compared to non-RASI antihypertensives in CKD patients.

synapsesocial.com/papers/6ae7d421edffb496294104c4 https://doi.org/10.1038/s41371-026-01241-7

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Renin-angiotensin system inhibitors and arterial stiffness in chronic kidney disease: results from the chronic renal insufficiency cohort

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Renin-angiotensin system inhibitors and arterial stiffness in chronic kidney disease: results from the chronic renal insufficiency cohort

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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