"We've been administering vitamin D injections for decades, but the potential benefit on survival has never been studied," says Ravi Thadhani, MD, MPH, director of clinical research in MGH Nephrology, the study's senior author. "This finding was a surprise and should force us to think more broadly about who should be treated."
Among the approximately 300,000 U.S. patients who receive dialysis for chronic kidney failure, the annual mortality rate is 20 percent, with cardiovascular disease the primary cause of death. In healthy individuals, the kidneys convert vitamin D from food and over-the-counter supplements into an activated form that the body can use. Kidney failure patient cannot utilize dietary vitamin D and must receive activated forms of the nutrient to avoid deficiency. Currently only 50 percent of kidney failure patients are treated with activated vitamin D, since the therapy is recommended only for those who also have elevated parathyroid levels.
In 2003 the same research group published a study finding that a particular form of activated vitamin D, paricalcitol, was associated with better survival than was calcitriol, previously the standard activated vitamin D therapy. For the current study, the reseachers asked the broader question of whether dialysis patients receiving any form of activated vitamin D therapy would live longer than those who did not.
Working with collaborators from Fresenius Medical Care North America, based in Lexington, Mass., the researchers compiled information on more than 50,000 patients who started dialysis at Fresenius centers across the country between 1996 and 1999 and were followed into 2002. More than 37,000 of those patients received injections of some form of activated vitamin D.
At the end of the two-year study period, 76 percent of those receiving any form of activated vitamin D were still alive, compared with 59 percent of those not receiving the therapy. That more than 20 percent reduction in mortality was seen across all categories of patients in the study - all races, ages and both genders. Even patients with elevated calcium or phosphorus levels, which often lead to the discontinuation of vitamin D therapy, lived longer if they received the treatment.
These results must be confirmed by follow-up studies - including randomized clinical trials - before more precise recommendations for treatment can be made, but the researchers note that even many patients who meet current guidelines for vitamin D therapy are not receiving it.
"While these results need to be verified, we at least need to be more aggressive in treating people that meet the current criteria," Thadhani says. "Thereafter we need to investigate what is the mechanism conferring this survival benefit. We are actively pursuing that with a focus on the effects on cardiovascular disease." Thadhani is an assistant professor of Medicine at Harvard Medical School.
The study's co-authors are first author Ming Teng, MD, MS, of Fresenius Medical Care; Myles Wolf, MD, MMSC, and Carlos Camargo, MD, of the MGH; Norma Ofsthun, PhD, and Michael Lazarus, MD, of Fresenius, and Miguel Hernan, PhD, of the Harvard School of Public Health. The research was supported entirely by internal MGH resources.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $450 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.