Heart failure: High levels of 2 substances in urine may increase risk

Evan Walker
Evan Walker TheMediTary.Com |
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Elevated levels of two substances may indicate a higher risk of new-onset heart failure. Herman Lumanog/Pacific Press/LightRocket via Getty Images
  • High, stable levels of urinary albumin excretion (UAE) and serum creatinine are associated with a higher risk of first-time heart failure, according to a new study.
  • Such levels of urinary albumin excretion were also tied to a higher risk of all-cause mortality.
  • However, the study could not establish that kidney dysfunction was the cause of heart failure or that both are not the products of comorbidities.
  • The study presents a potentially valuable diagnostic biomarker of heart failure.

People with consistently high levels of urinary albumin excretion (UAE) and serum creatinine in their urine are at higher risk of developing heart failure, a new study finds. This finding supports the known connection between kidney (renal) failure and heart failure.

For the study, researchers analyzed urine-sample data from nearly 7,000 Dutch participants. Individuals were 28 to 75 years of age at the start of the study, which followed them for 11 years.

According to the results, participants with stable and high levels of both UAE and serum creatinine in their urine samples had a higher risk of experiencing heart failure for the first time, while those with elevated levels of UAE had an increased risk of dying from all causes.

Similarly, high levels of serum creatinine were not found to be linked to all-cause mortality.

The study is an attempt to explore the potential health risks for people whose UAE and serum creatinine levels remain high over the long term instead of fluctuating as they do in most people. These findings may provide physicians with a new biomarker of susceptibility for heart failure.

The study is published in the European Journal of Heart Failure.

“Circulating in the bloodstream are lots of substances. Some of them are very tiny substances like, for example, sodium or glucose molecules, and some of them are large substances like proteins and antibodies, and that kind of thing,” explained Dr. Richard Wright, a cardiologist specializing in heart failure and transplantation cardiology at Providence Saint John’s Health Center, who was not involved in the study.

An important function of the kidneys is to filter extra fluid and waste, including acids produced by cells. When they are functioning properly, the kidneys help maintain a healthy balance of chemicals in one’s blood.

According to Dr. Wright, albumin is the most common protein circulating in the bloodstream. As a large molecule, “the filter of the kidney normally does not allow albumin to appear in the urine because it’s too large to make it through the filter.”

For example, smaller molecules such as sugar pass through to the urine easily.

As the health of kidneys and their filtration degrade, albumin passes into the urine. This makes its presence there a valuable marker of kidney dysfunction.

“Serum creatinine is a waste product of muscle use and is found in the blood. It is filtered out of the blood by the kidneys,” said Dr. Jayne Morgan, cardiologist and clinical director of the COVID Task Force at Piedmont Healthcare Corporation, who was also not involved in the study.

Higher levels of serum creatinine in the urine are often considered a sign of declining kidney function, though there are some exceptions.

Why creatinine levels may be misleading

Dr. Wright pointed out, for example, that weightlifters consume unusually high amounts of protein, so high levels of serum creatinine in their urine do not necessarily signify kidney dysfunction.

He added that there is some discussion in the heart failure community regarding older patients who typically have little muscle mass.

“Creatinine may not be as good a reflection of their kidney function because the creatinine is a derivative of broken-down protein. And if you don’t eat a lot of protein or have a lot of protein in your body, then the creatinine clearance may be misleading,” he said.

“This [study] continues to connect the kidney and the heart in a cardiorenal loop,” said Dr. Morgan. “Early albumin excretion is an opportunity to be alerted to not only developing kidney disease but heart failure risk as well.”

Dr. Morgan felt that the study’s findings might affect medications prescribed and medical follow-up, “providing the opportunity for preventive cardiac care, as opposed to interventive cardiac care.”

Dr. Andrew Clark, chair of clinical cardiology and head of the department of Academic Cardiology at Hull York Medical School, who was also not involved in the study, cautioned against basing all patient care on these new findings.

“The study is looking at associations between abnormalities in renal function and outcomes and cannot prove a causative link,” he said, pointing out a limitation of an observational study.

“In more-or-less any clinical scenario, worsening renal function is associated with worse outcomes, but that doesn’t mean it is the renal dysfunction causing the problem. Any causative association might be the other way round: heart failure potentially causes proteinuria, [abnormal amounts of protein in the urine],” explained Dr. Clark.

He also noted the link the researchers found between these substances and heart failure “might simply arise from the fact that the same precursors cause both outcomes. So, for example, high blood pressure and diabetes both cause renal and heart damage.”

“I think they did a good job, as good as can be done with this type of database. I do believe the conclusions are sound that people who are having worse renal function markers are more likely to develop heart failure. The question is then, ‘what do you do with that?’,” said Dr. Wright.

One thing, he suggested, was including a simple urine test measuring UAE and serum creatinine during checkups—a test he suspects few doctors prescribe.

“It’s an inexpensive, easy-to-do test, and it carries a lot of prognostic information,” he concluded.

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