Study Identifies Cardiac-Protection Mechanisms of Vitamin D in Kidney Failure

A study led by Michael Freundlich, M.D., professor of clinical pediatrics in the Division of Pediatric Nephrology, identified the renin-angiotensin system, which is known to regulate blood pressure, as a key molecular target through which vitamin D treatment improves cardiac hypertrophy in chronic kidney disease.

The study, “Paricalcitol Downregulates Myocardial Renin-Angiotensin and Fibroblast Growth Factor Expression and Attenuates Cardiac Hypertrophy in Uremic Rats,” was published online ahead of print September 26 in the American Journal of Hypertension.

Heart disease remains the primary cause of death in people with chronic kidney disease, which affects 26 million Americans and is usually associated with left ventricular hypertrophy, the enlargement of the left-side pumping chamber of the heart. Hypertrophy often precedes various adverse outcomes, such as congestive heart failure, cardiac arrhythmias and stroke.

Patients with chronic kidney disease who are treated with active vitamin D, or one of its analogs, like paricalcitol, have reduced mortality due largely to a reduction of their cardiac hypertrophy. However, the mechanisms by which vitamin D reduces heart hypertrophy in chronic kidney disease remains only partly understood and is the subject of intense research.

“Our study demonstrates increased expression of renin-angiotensin-system genes in the hypertrophic heart tissue of animals with kidney failure, and the ability of the vitamin D analog paricalcitol to correct the overexpression of these genes and prevent the development of cardiac hypertrophy without significantly affecting blood pressure,” Freundlich said. “These findings provide further insight on the cardioprotective properties of vitamin D observed in patients with CKD treated with this vitamin.”

The study is part of a collaborative ongoing research project involving investigators at the Miller School, the Institute of Scientific Investigations at University Hospital in Maracaibo, Venezuela, and the University of Chicago.

Other Miller School co-authors of the study include Wacharee Seeherunvong, M.D., assistant professor of clinical pediatrics, Jose R. Weisinger, M.D., professor of clinical medicine, and Christian Faul, Ph.D., assistant professor of medicine.

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