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Randomized Controlled Trial Multicenter Study
Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort.
- Basma Merhi, Theresa Shireman, Myra A Carpenter, John W Kusek, Paul Jacques, Marc Pfeffer, Madhumathi Rao, Meredith C Foster, S Joseph Kim, Todd E Pesavento, Stephen R Smith, Clifton E Kew, Andrew A House, Reginald Gohh, Daniel E Weiner, Andrew S Levey, Joachim H Ix, and Andrew Bostom.
- Division of Hypertension and Kidney Diseases, Department of Medicine, Rhode Island Hospital, Providence, RI.
- Am. J. Kidney Dis. 2017 Sep 1; 70 (3): 377-385.
BackgroundMild hyperphosphatemia is a putative risk factor for cardiovascular disease [CVD], loss of kidney function, and mortality. Very limited data are available from sizable multicenter kidney transplant recipient (KTR) cohorts assessing the potential relationships between serum phosphorus levels and the development of CVD outcomes, transplant failure, or all-cause mortality.Study DesignCohort study.Setting & ParticipantsThe Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial, a large, multicenter, multiethnic, controlled clinical trial that provided definitive evidence that high-dose vitamin B-based lowering of plasma homocysteine levels did not reduce CVD events, transplant failure, or total mortality in stable KTRs.PredictorSerum phosphorus levels were determined in 3,138 FAVORIT trial participants at randomization.ResultsDuring a median follow-up of 4.0 years, the cohort had 436 CVD events, 238 transplant failures, and 348 deaths. Proportional hazards modeling revealed that each 1-mg/dL higher serum phosphorus level was not associated with a significant increase in CVD risk (HR, 1.06; 95% CI, 0.92-1.22), but increased transplant failure (HR, 1.36; 95% CI, 1.15-1.62) and total mortality risk associations (HR, 1.21; 95% CI, 1.04-1.40) when adjusted for treatment allocation, traditional CVD risk factors, kidney measures, type of kidney transplant, transplant vintage, and use of calcineurin inhibitors, steroids, or lipid-lowering drugs. These associations were strengthened in models without kidney measures: CVD (HR, 1.14; 95% CI, 1.00-1.31), transplant failure (HR, 1.72; 95% CI, 1.46-2.01), and mortality (HR, 1.34; 95% CI, 1.15-1.54).LimitationsWe lacked data for concentrations of parathyroid hormone, fibroblast growth factor 23, or vitamin D metabolites.ConclusionsSerum phosphorus level is marginally associated with CVD and more strongly associated with transplant failure and total mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of phosphorus-lowering therapy on these hard outcomes may be warranted.Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.
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