Meta-analysis associates active vitamin D therapy with lower risk of mortality among kidney disease patients over up to eleven years of follow-up
Tuesday, October 8, 2013. On September 25, 2013 the journal BMC Nephrology published the results of a meta-analysis of chronic kidney disease patients which found an association between supplementation with active forms of vitamin D and a lower risk of dying over follow-up.
For their analysis, researchers at China's Tianjin Medical University selected 17 studies involving a total of 489,254 end stage renal disease patients receiving dialysis and three studies that included 2,603 chronic kidney patients not on dialysis. The subjects were treated with active vitamin D sterols that included alfacalcidol, doxercalciferol, calcitriol, maxacalcitol, falecalcitriol or paricalcitol. Follow-up periods ranging from 12 to 140 months.
In comparison with no treatment, subjects who received active vitamin D compounds had a 26% lower risk of dying from all causes over follow-up. Pooled analysis of dialysis patients associated active vitamin D therapy with a 20% lower adjusted risk of dying and among those not on dialysis, the risk was 41% lower compared to no treatment over follow-up. When cardiovascular mortality was examined, active vitamin D was associated with a 41% lower adjusted risk of death over follow-up.
"Vitamin D down regulates the renin-angiotensin system, improves insulin secretion and sensitivity, inhibits vascular smooth-muscle cell proliferation, protects normal endothelial cell function, modulates inflammatory processes, inhibits anticoagulant activity, and inhibits myocardial cell hypertrophy and proliferation," write Zhenfeng Zheng and colleagues. "These findings suggest that vitamin D may decrease mortality through multiple pathways."
"Large, well designed randomized trials of active vitamin D supplements with different doses are needed to elucidate the role of vitamin D supplementation in reducing mortality," they conclude.
Biochemistry professor Coleen E. Hayes and her associates at the University of Wisconsin-Madison tested the effect of calcitriol and vitamin D3 in mice with experimental autoimmune encephalitis, a condition in which demyelination of the nerves occurs as in MS. While vitamin D3 alone was not effective, the combination of calcitriol followed by supplementation with the vitamin resulted in improvement.
"All of the animals just got better and better, and the longer we watched them, the more neurological function they regained," Dr Hayes reported. "The treatment shows potential to help halt the disease's progress in humans, for whom currently available therapies have limited effectiveness. And in the long term they don't halt the disease process that relentlessly eats away at the neurons. So there's an unmet need for better treatments."
The experimental treatment was more effective than methylprednisone, which is used to treat neurological problems experienced by MS patients. "So, at least in the animal model, calcitriol is more effective than what's being used in the clinic right now," Dr Hayes noted.
"If the treatment works in people, patients with early symptoms of MS may never need to receive an official diagnosis," she added. "It's my hope that one day doctors will be able to say, 'We're going to give you an oral calcitriol dose and ramp up the vitamin D in your diet, and then we're going to follow you closely over the next few months. You're just going to have this one neurological episode and that will be the end of it. That's my dream."
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