What question did this study set out to answer?

This analysis aims to determine how loop diuretics interact with renin-angiotensin system inhibitors on kidney function in patients with chronic kidney disease.

January 22, 2026Open Access

Impact of Loop Diuretics on Long-Term Kidney Outcome

Key Result

In patients with advanced CKD taking loop diuretics, withdrawal of RASi led to a similar eGFR decline, contrasting with a steeper decline in those not taking diuretics.

Key Points

This analysis aims to determine how loop diuretics interact with renin-angiotensin system inhibitors on kidney function in patients with chronic kidney disease.
Analyzed data from the STOP-ACEi trial participants with eGFR <30 ml/min/1.73m²
Used repeated-measures, mixed-effects linear regression models for eGFR assessment
Employed Cox models to evaluate time-to-event outcomes like ESKD and KRT
At 3-years, those with loop diuretics showed a mean eGFR of 12.3 (±1.1) when stopping RASi and 10.1 (±1.2) when continuing it, favoring stopping RASi by +2.2 (95% CI, -0.9 to +5.4)
Among those not receiving loop diuretics, eGFR was 8.8 (±0.8) for discontinuing RASi and 11.6 (±0.8) for continuing, favoring continued RASi by -2.8 (95% CI, -4.9 to -0.8)
55% of loop diuretics users developed ESKD/KRT against 61% of non-users, with mortality rates of 17% and 7% respectively.

Structured PICO

Does stopping RASi improve eGFR over 3 years in patients with advanced CKD, and is this effect modified by loop diuretic use?

Population

411 patients with advanced progressive chronic kidney disease (eGFR <30ml/min/1.73m2)

Intervention

Stopping renin-angiotensin system inhibitors (RASi)

Comparator

Continuing renin-angiotensin system inhibitors (RASi)

Outcome

eGFR over 3-yearssurrogate

In patients with advanced CKD, withdrawing RASi therapy leads to a steeper decline in kidney function among those not taking loop diuretics, whereas this detrimental effect is not observed in those on loop diuretics.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Background: In the STOP-ACEi trial, patients with advanced CKD were randomised to continue or stop renin–angiotensin system inhibitors (RASi) and showed no difference in kidney outcomes. This post-hoc analysis investigates interactions with loop diuretic use. Methods: Patients with eGFR<30ml/min/1.73m 2 and progressive CKD were randomized, to stop or continue RASi. Primary outcome was eGFR over 3-years using repeated-measures, mixed-effects linear regression, random-slope models. Cox models were used to calculate hazard ratios for time-to-event outcomes, including ESKD and KRT. Results: At baseline, eGFR, arterial pressure and proteinuria were similar for 133 patients taking loop diuretics and 278 who were not. Those receiving loop diuretics at randomization, least-squares mean (±SE) eGFR at 3-years was 12.3 (±1.1) for those stopping compared to 10.1 (±1.2) for those continuing RASi, trend favouring stopping RASi (+2.2; 95% CI, –0.9 to +5.4), but eGFR slope over 3-years was similar (-7.2 vs -7.7 ml/min/1.73m 2 ). Those not receiving loop diuretics, eGFR at 3-years was 8.8 (±0.8) and 11.6 (±0.8) (discontinue and continue RASi groups), a difference favouring continuing RASi (–2.8; 95% CI, –4.9 to -0.8), and a steeper eGFR slope for those discontinuing RASi (-9.9 vs -7.6 ml/min/1.73m 2 ). The interaction between loop diuretic use and the effect of RASi on eGFR at 3-years and the three-way interaction between diuretic subgroup, effect of RASi and time were both statistically significant (p=0.01 and p=0.04 respectively). Of patients taking loop diuretics, 73 (55%) developed ESKD/KRT, and 23 (17%) died. Of patients not taking loop diuretics, 170 (61%) developed ESKD/KRT and 19 (7%) died. Conclusions: Withdrawal of RASi was associated with a steeper decline in eGFR over 3-years in those not receiving loop diuretics but this was not observed in those who were taking loop diuretics. Patients receiving loop diuretics had a high mortality. These data support the need for randomised trials investigating the efficacy and safety of loop diuretics in patients with advanced CKD.