What is the clinical evidence from this study?

Study design: Cohort. Population: Chronic kidney disease (n=157). Intervention: Prior ARNI use vs. Prior ARB use. Primary outcome: Incidence of an initial dip, defined as a ≥ 5% decline in eGFR within 2 months after SGLT2 inhibitor initiation (OR 0.30, 95% CI 0.10-0.89, p=0.02).

What question did this study set out to answer?

This study investigates the effect of prior ARNI use on the initial decline in eGFR after starting SGLT2 inhibitors in chronic kidney disease patients.

August 6, 2026Clinical and Experimental NephrologyOpen Access

Association of prior Angiotensin receptor-neprilysin inhibitor use with the initial eGFR dip after initiation of SGLT2 inhibitors in patients with chronic kidney disease

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Why the study?

The impact of prior ARNI use on the initial eGFR dip following SGLT2 inhibitor initiation in patients with chronic kidney disease remains unclear.

Does prior ARNI use reduce the initial eGFR dip after SGLT2 inhibitor initiation in patients with chronic kidney disease compared to prior ARB use?

Population

157 patients with chronic kidney disease newly starting SGLT2 inhibitors

Comparison

Prior ARNI use vs prior ARB use

Design

Retrospective cohort study

Follow-up

1 year

Key result

Prior ARNI use was independently associated with a lower risk of an initial eGFR dip following SGLT2 inhibitor initiation compared to prior ARB use (OR 0.30).

Authors

YUYusuke Ushio HKHiroshi Kataoka RTRina Takahashi

Discussion

Member takes

Overview

Prior ARNI use may blunt SGLT2i eGFR dip in CKD; leaves open effects on long-term outcomes.

Key Points

This study investigates the effect of prior ARNI use on the initial decline in eGFR after starting SGLT2 inhibitors in chronic kidney disease patients.
Retrospective evaluation of 157 chronic kidney disease patients starting SGLT2 inhibitors between 2022 and 2025.
Patients classified into ARNI and ARB groups to compare outcomes.
Primary outcome measured was incidence of initial dip defined as ≥ 5% decline in eGFR.
Initial dip incidence was 30.0% in the ARNI group vs. 46.5% in the ARB group (p = 0.10).
Prior ARNI use was linked to a lower risk of the initial dip (odds ratio 0.30, 95% CI 0.10-0.89, p = 0.02).
No significant difference in longitudinal eGFR or urine protein changes at 1 year.

Study Design

Type

Cohort (n=157)

Multicenter

Structured PICO

Does prior ARNI use reduce the initial eGFR dip after SGLT2 inhibitor initiation in patients with chronic kidney disease compared to prior ARB use?

Population

157 patients with non-dialysis chronic kidney disease who newly initiated SGLT2 inhibitors while on prior ARNI or ARB therapy, followed for 1 year.

Exposure

Prior Angiotensin receptor-neprilysin inhibitor (ARNI) therapy before initiating SGLT2 inhibitors

Comparator

Prior angiotensin receptor blocker (ARB) therapy before initiating SGLT2 inhibitors

Outcome

Incidence of an initial dip, defined as a ≥ 5% decline in eGFR within 2 months after SGLT2 inhibitor initiationsurrogate

Main Result

Odds Ratio: 0.3 (95% CI 0.1–0.89)

Absolute Event Rate: 30% vs 46.5%

p-value: p=0.02

Prior ARNI use may mitigate the initial eGFR dip following SGLT2 inhibitor initiation in patients with CKD, though it does not significantly alter the 1-year eGFR trajectory.

Limitations

Retrospective design with limited sample size and event number
Generally mild proteinuria and relatively small proportion of patients with diabetic kidney disease
Potential residual or unmeasured confounding, including confounding by indication
Lack of consideration of ARNI or ARB doses and dose changes
Use of a ≥ 5% eGFR decline threshold instead of a more clinically meaningful ≥ 10% cutoff due to limited events
True nadir eGFR may have been missed as the cohort consisted mainly of outpatients
Generally mild proteinuria and a relatively small proportion of patients with diabetic kidney disease
Potential residual or unmeasured confounding
Confounding by indication and treatment selection dependent on physician judgment

Cite This Study

Ushio et al. (2026) conducted a cohort in Chronic kidney disease (n=157). Prior ARNI use vs. Prior ARB use was evaluated on Incidence of an initial dip, defined as a ≥ 5% decline in eGFR within 2 months after SGLT2 inhibitor initiation (OR 0.30, 95% CI 0.10-0.89, p=0.02). Prior ARNI use was independently associated with a lower risk of an initial eGFR dip following SGLT2 inhibitor initiation compared to prior ARB use (OR 0.30).

synapsesocial.com/papers/6a7437ba764cddc9499d54dd https://doi.org/10.1007/s10157-026-02928-4

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August 6, 2026Clinical and Experimental NephrologyOpen Access

Association of prior Angiotensin receptor-neprilysin inhibitor use with the initial eGFR dip after initiation of SGLT2 inhibitors in patients with chronic kidney disease

View Full Paper

Ask AI

Bookmark

Why the study?

The impact of prior ARNI use on the initial eGFR dip following SGLT2 inhibitor initiation in patients with chronic kidney disease remains unclear.

Does prior ARNI use reduce the initial eGFR dip after SGLT2 inhibitor initiation in patients with chronic kidney disease compared to prior ARB use?

Population

157 patients with chronic kidney disease newly starting SGLT2 inhibitors

Comparison

Prior ARNI use vs prior ARB use

Design

Retrospective cohort study

Follow-up

1 year

Key result

Prior ARNI use was independently associated with a lower risk of an initial eGFR dip following SGLT2 inhibitor initiation compared to prior ARB use (OR 0.30).

Authors

YUYusuke Ushio HKHiroshi Kataoka RTRina Takahashi

Discussion

Member takes

Overview

Prior ARNI use may blunt SGLT2i eGFR dip in CKD; leaves open effects on long-term outcomes.

Key Points

This study investigates the effect of prior ARNI use on the initial decline in eGFR after starting SGLT2 inhibitors in chronic kidney disease patients.
Retrospective evaluation of 157 chronic kidney disease patients starting SGLT2 inhibitors between 2022 and 2025.
Patients classified into ARNI and ARB groups to compare outcomes.
Primary outcome measured was incidence of initial dip defined as ≥ 5% decline in eGFR.
Initial dip incidence was 30.0% in the ARNI group vs. 46.5% in the ARB group (p = 0.10).
Prior ARNI use was linked to a lower risk of the initial dip (odds ratio 0.30, 95% CI 0.10-0.89, p = 0.02).
No significant difference in longitudinal eGFR or urine protein changes at 1 year.

Study Design

Type

Cohort (n=157)

Multicenter

Structured PICO

Does prior ARNI use reduce the initial eGFR dip after SGLT2 inhibitor initiation in patients with chronic kidney disease compared to prior ARB use?

Population

157 patients with non-dialysis chronic kidney disease who newly initiated SGLT2 inhibitors while on prior ARNI or ARB therapy, followed for 1 year.

Exposure

Prior Angiotensin receptor-neprilysin inhibitor (ARNI) therapy before initiating SGLT2 inhibitors

Comparator

Prior angiotensin receptor blocker (ARB) therapy before initiating SGLT2 inhibitors

Outcome

Incidence of an initial dip, defined as a ≥ 5% decline in eGFR within 2 months after SGLT2 inhibitor initiationsurrogate

Main Result

Odds Ratio: 0.3 (95% CI 0.1–0.89)

Absolute Event Rate: 30% vs 46.5%

p-value: p=0.02

Prior ARNI use may mitigate the initial eGFR dip following SGLT2 inhibitor initiation in patients with CKD, though it does not significantly alter the 1-year eGFR trajectory.

Limitations

Retrospective design with limited sample size and event number
Generally mild proteinuria and relatively small proportion of patients with diabetic kidney disease
Potential residual or unmeasured confounding, including confounding by indication
Lack of consideration of ARNI or ARB doses and dose changes
Use of a ≥ 5% eGFR decline threshold instead of a more clinically meaningful ≥ 10% cutoff due to limited events
True nadir eGFR may have been missed as the cohort consisted mainly of outpatients
Generally mild proteinuria and a relatively small proportion of patients with diabetic kidney disease
Potential residual or unmeasured confounding
Confounding by indication and treatment selection dependent on physician judgment

Cite This Study

synapsesocial.com/papers/6a7437ba764cddc9499d54dd https://doi.org/10.1007/s10157-026-02928-4

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