Stopping RAS inhibitors is associated with a risk of adverse outcomes in patients with chronic kidney disease

Small studies have suggested that a group of medications called RAS inhibitors may be harmful in people with advanced kidney disease, so physicians often discontinue treatment in such patients. Researchers at Karolinska Institutet now show that while cessation of treatment is associated with a lower risk for seeking dialysis, it is also associated with a higher risk of cardiovascular events and death. The results are published in Journal of the American Nephrology Society.

Chronic kidney disease (CKD) affects about ten percent of the world’s population. Hip-suffering is the most common comorbidity. Patients with CKD are at increased risk for cardiovascular disease and death.

Advanced kidney disease is classified as ‘significantly reduced kidney function’ and is defined as the ability of the kidneys to cleanse the blood less than about 30 percent of normal for a young adult. In some patients, CKD progresses to the point that it requires dialysis or transplantation as a renal replacement to prolong life.

Renin-angiotensin system protectors (RAS protectors), include both ACE inhibitors (ending in ‘pril’) and ARBs (ending in ‘sartans’) , are common medications for the treatment of hip wasting, cardiovascular disease, heart failure and CKD. However, their efficacy and safety in patients with advanced CKD are not well known, as this population was underrepresented in the landmark randomized trials.

“Small studies have suggested that discontinuation of RAS inhibitors in these patients may promote renal activity and delay the need for renal transplant therapy,” says Edouard Fu, MD and PhD candidate at the Department of Clinical Epidemiology, Leiden University Medical Center and the study’s first author. “However, stopping these medications could also increase the risk of heart attacks, stroke and death. We wanted to help practitioners evaluate the risks and benefits of this decision, and Swedish Quality Records is the perfect place to answer this question. “

Researchers at Karolinska Institutet and colleagues have conducted an epidemiological study using data from the Swedish Renal Registry to evaluate more than 10,000 patients with advanced CKD who have acquired RAS protectors over the decade gone.

Comparing morbidity and mortality rates in patients who were discontinued with those who followed the drug regimen, the researchers found that discontinuation of these medications was associated with an eight percent lower risk for requiring renal replacement therapy.

However, stopping was also associated with a thirteen percent higher risk of death at five years, and a twelve percent higher risk for suffering a heart attack or stroke.

The use of RAS inhibitors in patients with advanced CKD is controversial, and many doctors deregister them. Instead of routinely stopping treatment, our results show that the case is complex and that doctors need to emphasize the protective effects of RAS inhibitors on the cardiovascular system against the possible damage to the kidneys. Until clinical trials are conducted, this evidence supports the continued use of this life-saving treatment in patients with advanced CKD who are doing well on the medications. “

Juan Jesus Carrero, Principal Investigator, Professor, Department of Medical Epidemiology and Biostatistics, Karolinska Institute in Sweden

He says these medications sometimes need to be stopped for other reasons, for example, if patients have high blood potassium levels that do not respond to management.

The study was conducted in collaboration with Leiden University Medical Center (The Netherlands), McMaster University (Canada) and the London (UK) School of Hygiene and Tropical Medicine. It has been supported by grants from the Swedish Research Council, the Swedish Heart and Lung Foundation, and the Westman Foundation. Some authors receive funding and honoraria from pharmaceutical companies for issues unrelated to this study; the scientific paper lists potential conflicts of interest as a whole.