Sunday, April 21, 2013

New Kidney Function Tied to Vitamin D Status

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Low vitamin D after a kidney transplant is associated with worse kidney function and increased fibrosis, researchers reported.
In a single-institution prospective cohort, low 25-hydroxyvitamin D (25-OHD) levels 3 months after transplant predicted a lower measured glomerular filtration rate (mGFR) after a year, according to Frank Bienaimé, MD, and colleagues at the Université Paris Descartes in Paris.
Low 25-OHD levels also predicted increased interstitial fibrosis progression, but not death or loss of the graft, Bienaimé and colleagues reported online in the Journal of the American Society of Nephrology.
An "important corollary" of the findings is the possible therapeutic effect of vitamin D supplements in end-stage renal disease patients getting a transplant, Bienaimé and colleagues concluded.
"This result suggests that maintaining vitamin D concentration within the normal range would prevent renal function deterioration after renal transplantation," Bienaimé said in a statement.
"Vitamin D supplementation, a simple and inexpensive treatment, may improve transplantation outcomes," he added. He and colleagues said there's a need for randomized controlled trials that would evaluate the effect of supplements and measure the magnitude of any benefit.
Vitamin D plays several important physiological roles, but kidney recipients often have low levels of 25-OHD and hormonally active calcitriol or 1,25 dihydroxyvitamin D (1,25-OHD), the researchers noted.
Those levels are potentially modifiable, but it's not known if levels affected kidney function or transplant outcome. To help clarify the issue, Bienaimé and colleagues looked at 634 patients who had a kidney transplant between January 2005 and June 2010.
At their institution, standard care includes measurement of GFR and mineral metabolism variables – including 25-OHD -- 3 and 12 months after transplantation.
Overall, 25-OHD concentrations were low, with a median concentration of 13 ng/mL, and were lower than 30 ng/mL in 91.7% of patients.
On the other hand, concentrations of calcitriol were within the normal range in most patients, they found.
After a median follow-up of 48.6 months, 19 patients were lost to follow-up, 30 patients had lost their graft, 28 patients had died with a functioning graft, and three had died after losing their kidney.
A Kaplan-Meier analysis showed that the risk of death was similar regardless of 3-month levels of 25-OHD and calcitriol, while regression analysis showed no association between vitamin D and the risk of death.
Similarly, there was no association between graft loss and the 3-month levels of either hormone, the researchers reported.
On the other hand, patients with 3-month 25-OHD levels below 15 ng/mL -- the definition of insufficient in this analysis -- had an average 12-month mGFR of 55 mL/min.
Patients with sufficient 3-month 25-OHD levels had a 12-month mGFR of 59 mL/min for a difference that was significant (P=0.006).
Multivariate analysis showed that two factors -- donor age and 3-month 25-OHD concentrations -- were independently and significantly associated with progressive interstitial fibrosis and tubular atrophy (P=0.01).
Bienaimé and colleagues cautioned that the low incidence of death and graft loss means the study was underpowered to assess renal survival. Also the follow-up was relatively short and "precludes conclusions" about the effect of 25-OHD levels on GFR after the first year of transplantation.
However, they noted that a "striking" finding in their study was the association between 25-OHD, and the lack of one for 1,25-OHD, and allograft function at 12 months plus interstitial fibrosis-tubular atrophy progression from 3 months to 1 year after transplantation.
"Our finding that low concentration of 25-OHD but not of 1,25-OHC predicted GFR decline and [interstitial fibrosis-tubular atrophy] progression in the first year after kidney transplantation raises important questions," they wrote.
They pointed out that 25-OHD is generally considered an inactive compound that reflects vitamin D stocks while circulating 1,25-OHD is thought to represent biologically active vitamin D.
In this study, parathyroid levels correlated negatively with 25-OHD, but not with 1,25-OHD concentration, "suggesting that circulating 25-OHD is the main determinant of vitamin D receptor signaling in parathyroid cells," they wrote.
The authors did not report any external support for the study or report any conflicts of interest.
Primary source: Journal of the American Society of Nephrology
Source reference:
Bienaimé F, et al "Vitamin D status and outcomes after renal transplantation" J Am Soc Nephrol 2013; 24.
Michael Smith
North American Correspondent
North American Correspondent for MedPage Today, is a three-time winner of the Science and Society Journalism Award of the Canadian Science Writers' Association. After working for newspapers in several parts of Canada, he was the science writer for the Toronto Star before becoming a freelancer in 1994. His byline has appeared in New ScientistScience, the Globe and MailUnited Press International,Toronto LifeCanadian Business, the Toronto StarMarketing Computers, and many others. He is based in Toronto, and when not transforming dense science into compelling prose he can usually be found sailing.

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