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Kidney Disease Research Updates
Spring 2012

NIH Researchers Identify Elusive Connection Between CKD and CVD

 

Image of a stethoscope, an electrocardiogram printout, and an adult male with hand resting on chin.

 

People with chronic kidney disease (CKD) are more likely to die from a heart attack or stroke than they are to progress to kidney failure requiring dialysis or a transplant. It is well established that CKD is associated with an increased risk of cardiovascular disease (CVD).

Until recently, however, researchers have not been able to identify the precise mechanism that would explain the connection between the two diseases. But a recent study led by researchers at the University of Miami and funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health indicates that elevated levels of a certain hormone partially explain the connection between CKD and CVD. Results are in the November 1, 2011, issue of the Journal of Clinical Investigation.

In a previous study of patients beginning hemodialysis for treatment of kidney failure, individuals with elevated blood levels of the hormone fibroblast growth factor 23 (FGF23) were found to be at nearly six times greater risk of death compared to those with lower levels. However, the hormone had not been tested in the much larger population of patients with less advanced CKD. Then, in a study reported in the June 2011 Journal of the American Medical Association, researchers reported that patients with CKD and high levels of FGF23 are at three times higher risk of death compared to patients with lower levels of the hormone.

In the study reported in November, senior study author Myles Wolf, M.D., M.M.Sc., and colleagues at the University of Miami found that FGF23 plays a direct role in increasing the risk of CVD in people with CKD. Researchers have known that the presence of a high level of FGF23 is associated with the presence of left ventricular hypertrophy (LVH), enlargement of the left pumping chamber in the heart, an important mechanism in CVD. But it was not known whether FGF23 was the specific cause of LVH. Wolf and colleagues injected FGF23 into the bloodstream or into the heart of wild-type mice and found that these mice developed LVH. Furthermore, injecting an FGF23 blocker into mice with chronic kidney disease prevented the development of LVH.

The researchers also measured FGF23 levels in baseline plasma samples from thousands of individuals with CKD who underwent echocardiography 1 year later. The median plasma FGF23 level was more than three-fold greater than that in previous studies of predominantly non-CKD populations. Furthermore, the people with the largest mass on the left side of the heart corresponded with the people who had the highest levels of FGF23. Even after adjusting for several factors—such as weight, smoking, systolic blood pressure, and history of cardiovascular disease— FGF23 was still found to be an independent risk factor for LVH.

Furthermore, Wolf and colleagues determined that elevated FGF23 was associated with increased risk of new-onset LVH in CKD. The researchers followed 411 participants with CKD and normal sized hearts, measuring levels of FGF23 in their blood at baseline. After 3 years, 84 participants developed new-onset LVH. The researchers found that the participants with the highest levels of FGF23 had the greatest risk of developing LVH, even in patients with normal blood pressure.

“While many factors are involved in the complex pathogenesis of LVH, the results of this study indicate that FGF23 is one contributing molecular mediator,” concluded Wolf and colleagues.

The findings are based on data from 3,879 racially diverse participants with CKD who enrolled in the NIDDK-supported, multi-center, observational Chronic Renal Insufficiency Cohort (CRIC) Study between June 2003 and September 2008. During a median follow up period of 3.5 years, 266 patients died and 410 developed kidney failure.

An estimated 23 million American adults have CKD, and nearly 400,000 people in the United States and 2 million worldwide depend on dialysis to treat kidney failure. CKD costs the nation $57.5 billion per year, or roughly 23 percent of total Medicare expenditures, and end-stage renal disease carries a cost of $39.5 billion.

This research was also supported by the National Institutes of Health’s National Center for Research Resources.

For more information about the CRIC Study, visit http://archives.niddk.nih.gov/patient/cric/cric.aspx.

The National Kidney Disease Education Program, part of the NIDDK, offers health information about CKD. For more information, visit www.nkdep.nih.gov.

 

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NIH Publication No. 12–4531
June 2012

Page last updated June 26, 2012


 

The National Kidney and Urologic Diseases Information Clearinghouse is a service of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

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