Effect Of Stopping RAS Inhibitors In Patients With Chronic Kidney Disease

In patients with chronic kidney disease, stopping RAS inhibitors is linked to a lower risk of dialysis but it increases the risk of cardiovascular events, and death.

Certain small studies suggest that a group of medications called RAS inhibitors which are used for the treatment of hypertension, may be harmful in patients with advanced chronic kidney disease. Therefore physicians often stop the treatment with these drugs in such patients.

Research conducted at Karolinska Institutet shows that although stopping RAS inhibitors is linked to a lower risk of requiring dialysis, it is also linked to a higher risk of cardiovascular events, and death.

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‘In patients with chronic kidney disease, stopping RAS inhibitors is linked to a lower risk of dialysis but it increases the risk of cardiovascular events, and death.’
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The research conducted at Karolinska Institutet is published in the The Journal of the American Society of Nephrology.

Approximately ten percent of the global population suffers from Chronic kidney disease (CKD) and hypertension is the most common co morbid condition. Patients suffering from CKD have an increased risk of cardiovascular disease, and death.

Advanced chronic kidney disease classified as 'severely decreased kidney function' is defined as the kidney's ability to remove the toxic waste from the blood being less than approximately 30 percent of normal for a young adult. In certain cases, CKD progresses to the point that dialysis or transplantation is required as a kidney replacement therapy to prolong life.

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Renin-angiotensin system inhibitors (RAS inhibitors) include class of drugs like Angiotensin Converting Enzyme (ACE) inhibitors (ending in 'pril') and Angiotensin Receptor Blockers (ARBs ending in 'sartan'), are the commonly used medications for the treatment of hypertension, cardiovascular disease, heart failure and CKD. However, not enough is known about the efficacy and safety of these medications in patients with advanced CKD, since this population was underrepresented in the landmark randomized trials.

Study’s first author, Edouard Fu, MD and PhD Candidate at the Department of Clinical Epidemiology, Leiden University Medical Center said, "Small-scale studies have suggested that stopping RAS inhibitors in these patients may improve kidney function and delay the need for kidney replacement therapy. However, stopping these medications may also increase the risk of heart attacks, stroke and death. We wanted to help practitioners by evaluating the risks and benefits of this decision, and Swedish Quality Registers are uniquely suited to answer this question."

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The researchers conducted an epidemiological study using data from the Swedish Renal Registry to evaluate over 10,000 patients with advanced CKD who received RAS inhibitors over the past decade.

When the morbidity and mortality rates were compared between the patients whose treatment was discontinued with those who continued the drug regimen, the researchers found that discontinuing these medications were associated with an eight percent lower risk of requiring kidney replacement therapy.

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However, discontinuing the drug lead to a thirteen percent higher risk of death at five years, and a twelve percent higher risk of suffering a heart attack or stroke.

Principal investigator Juan Jesus Carrero, professor at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet in Sweden said, "The use of RAS inhibitors in patients with advanced CKD is controversial, and many doctors deprescribe them. 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. 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."

If patients have persistently high blood potassium levels that don't respond to management, these medications can be stopped.

Source-Medindia