Loop diuretics are used to manage the hypertension and congestion often caused by chronic kidney disease (CKD), but they also activate the renin-angiotensin system, leading to potential cardiovascular and kidney damage. Renin-angiotensin system (RAS) inhibitors may help protect against this damage.
In a post hoc analysis published in Kidney360, Sunil Bhandari, MBChB, MRCP, PhD, MClinEd, and colleagues investigated the interaction between RAS inhibitors and loop diuretics among patients with advanced CKD. The study used data from the STOP-ACEi (angiotensin-converting enzyme inhibitor) trial, in which patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2 and progressive CKD were randomized to either stop or continue treatment with a RAS inhibitor.
The researchers compared outcomes between the 133 patients who were being treated with loop diuretics and 278 who were not. At baseline, eGFR, arterial pressure, and proteinuria were similar between these two groups. However, the researchers identified differences in kidney function at 3 years relating to whether patients stopped or continued treatment with a RAS inhibitor.
Among patients being treated with loop diuretics, researchers observed a trend toward better kidney function in those who stopped taking a RAS inhibitor, with a least-squares mean eGFR (± standard error) of 12.3 (±1.1) at 3 years in this group compared with 10.1 (±1.2) for those continuing treatment with a RAS inhibitor. However, the eGFR slope over this period was similar regardless of RAS inhibitor discontinuation (–7.2 vs –7.7 mL/min/1.73 m2). Among participants not receiving loop diuretics, worse outcomes were observed for those who stopped treatment with a RAS inhibitor, with eGFR of 8.8 (±0.8) compared with 11.6 (±0.8) among those who continued the treatment. A steeper eGFR slope was noted among those who discontinued treatment with a RAS inhibitor (–9.9 vs –7.6 mL/min/1.73 m2).
In addition, those taking loop diuretics had poorer outcomes in terms of mortality, with 55% developing end-stage kidney disease (ESKD) or initiating kidney replacement therapy (KRT) and 17% dying, whereas 61% of those not taking loop diuretics developed ESKD or initiated KRT, and only 7% died.
In summary, the interaction between treatment with a loop diuretic and the effect of a RAS inhibitor on eGFR was statistically significant at 3 years (P=0.01). These findings indicate that treatment with a RAS inhibitor leads to different outcomes depending on whether a patient is receiving loop diuretics, with evidence showing that treatment with loop diuretics and a RAS inhibitor in combination can improve patient outcomes but also that loop diuretics may have adverse effects on mortality. The researchers conclude that further research is needed to investigate the efficacy and safety of loop diuretic therapy among patients with advanced CKD.