Study paves the way for new therapeutic targets which can potentially improve heart disease in patients with end-stage kidney failure

Oct 4 2005

Night-time hemodialysis patients may have a greater capacity to repair their hearts and blood vessels compared to those on conventional dialysis three times a week, according to a study in the October issue of the American Journal of Physiology - Renal Physiology, published by the American Physiological Society.

"This study paves the way for new therapeutic targets which can potentially improve heart disease in patients with end-stage kidney failure," said Christopher T. Chan, the lead author of the study entitled "Nocturnal hemodialysis is associated with restoration of impaired endothelial progenitor cell biology in end-stage renal disease." Chan is a nephrologist at Toronto General Hospital (TGH) University Health Network, as well as the medical director of the Home Hemodialysis Program at TGH and assistant professor of medicine, University of Toronto. Co-investigator Subodh Verma of the Division of Cardiac Surgery, St. Michael's Hospital and assistant professor, University of Toronto, studies endothelial function.

This study specifically examined endothelial progenitor cells (EPCs) which reside in the bone marrow and contribute to the regeneration and repair of blood vessel walls, and may well play a significant role in generating new blood vessels at the site of an injury. Studies have shown that an infusion of EPCs into the heart after a heart attack or into limbs that have constricted blood flow do improve blood flow and aid in healing injured tissue.

"Endothelial progenitor cells are like 'handymen' entering the bloodstream to get into areas of blood vessel injury to help repair the damage which occurs on a daily basis," Chan explained, adding that depletion or reduced function of these cells likely contributes to blood vessel disease. "If we can manipulate EPCs to directly target vascular and cardiac injury, we may unlock an important mechanism by which we can address the high cardiovascular morbidity and mortality of this patient population," Chan said.

The study found that there was a five-fold decrease in EPCs in patients on conventional dialysis compared to the healthy participants and the patients on night hemodialysis. Moreover, patients on conventional hemodialysis also had higher blood pressure than patients on night-time dialysis (mean of 143 vs.128) and significantly higher left ventricular mass index (LVMI) scores, indicating abnormal left ventricular heart mass.

Chan and Verma studied and compared three groups of patients cross-matched for age, gender and reasons for dialysis: 12 conventional dialysis patients, 10 nocturnal hemodialysis patients and 10 healthy patients who do not need dialysis.

The four key outcome measures included: Numbers of EPCs circulating in the blood stream; migration function of these cells, measuring whether the cells were able to migrate into the blood stream to get to an injury site; LVMI, which measures the weight of the heart (a thickened heart cannot pump blood efficiently and results in eventual heart failure); and blood pressure.

Results on all measures showed a significant difference between the patients on conventional hemodialysis and the two other groups: those patients receiving night hemodialysis and the healthy control group. Compared with the healthy participants and the ones on night hemodialysis, EPC number and migration function were markedly impaired in conventional dialysis patients, along with a poorer LVMI and higher blood pressure. In contrast, EPC number and migration function were normal in night-time dialysis patients.

"These results show that with night-time dialysis, the numbers and function of these specific cells are similar to our healthy study participants," said Chan, "and given the critical importance of these cells in vascular repair and regeneration, this study adds support to the growing evidence of cardiovascular benefits of night-time hemodialysis."

Verman note that "In the Sept. 8, 2005 issue of the The New England Journal of Medicine, we learned that the number of circulating endothelial progenitor cells predicts the occurrence of cardiovascular events and death from cardiovascular causes, further reinforcing the importance of the current findings."

Cardiovascular disease is the principal cause of death in end-stage renal (kidney) disease patients, with many patients also having high blood pressure and diabetes. However, these additional illnesses only partially explain the high cardiovascular risk associated with end-stage renal failure. In particular, conventional dialysis does not substantially decrease this risk. Of the 15 – 20% annual mortality rate of conventional dialysis patients, about 50% is due to cardiovascular diseases.

Chan noted that nocturnal hemodialysis is the more optimal therapy for patients with end-stage renal disease since it more closely mimics what our own kidneys do in our bodies.

The increased frequency and duration of night hemodialysis (about six sessions per week, approximately 8 hours per session) has previously shown to improve blood pressure, lower use of anti-hypertensive medications and improve cardiovascular measures compared to patients on conventional dialysis. Additionally, patients on the thrice-weekly conventional dialysis (about four hours per session) have complications such as abnormal thickness of the heart, low energy and retention of fluids in the body, necessitating a strict diet and liquid-intake regimen.

TGH currently has 67 patients on nightly home hemodialysis, making it one of the largest programs in the world. Patient training for nightly home hemodialysis takes from six to eight weeks, and includes hands-on learning about the dialysis machine, medications, problem-solving in the event of a machine malfunction, IV medications and blood work.

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