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Stopping RAS Inhibitors May Worsen Outcomes in CKD

FRIDAY, Jan. 15, 2021 -- The decision to stop renin-angiotensin system (RAS) inhibitor therapy in patients with advanced chronic kidney disease (CKD) should take into account both cardiovascular risk and the risk for kidney replacement therapy, according to a study published online Dec. 28 in the Journal of the American Society of Nephrology.

Edouard L. Fu, from Leiden University Medical Center in the Netherlands, and colleagues assessed whether outcomes are affected by stopping RAS inhibitor therapy in patients with advanced chronic kidney disease. The Swedish Renal Registry (2007 to 2017) was used to identify 10,254 nephrologist-referred patients (median age, 72 years; 36 percent women) who reached advanced CKD (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) while on RAS inhibitor therapy.

The researchers found that 15 percent of patients stopped RAS inhibitors within six months. Compared with continuing therapy, stopping RAS inhibitors was associated with a higher absolute five-year risk for death (40.9 versus 54.5 percent) and major adverse cardiovascular events (47.6 versus 59.5 percent) and a lower risk for kidney replacement therapy (36.1 versus 27.9 percent). Whether patients stopped at higher or lower eGFR, after adjustment and stratification for albuminuria and potassium, and when modeling RAS inhibition as a time-dependent exposure using a marginal structural model, results remained consistent across prespecified subgroups.

"Rather than routinely discontinuing treatment, our results show that the issue is a complex one and that doctors must carefully weigh the protective effects of RAS inhibitors on the cardiovascular system against the potential harms on the kidneys," a coauthor said in a statement. "Until clinical trials are performed, this evidence supports continued use of this lifesaving therapy in patients with advanced CKD who are doing well on the medications."

Several authors disclosed financial ties to the pharmaceutical industry.

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