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Randomized Controlled Trial
. 2017 Sep;70(3):377-385.
doi: 10.1053/j.ajkd.2017.04.014. Epub 2017 Jun 2.

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  1 , Theresa Shireman  2 , Myra A Carpenter  3 , John W Kusek  4 , Paul Jacques  5 , Marc Pfeffer  6 , Madhumathi Rao  7 , Meredith C Foster  7 , S Joseph Kim  8 , Todd E Pesavento  9 , Stephen R Smith  10 , Clifton E Kew  11 , Andrew A House  12 , Reginald Gohh  1 , Daniel E Weiner  7 , Andrew S Levey  7 , Joachim H Ix  13 , Andrew Bostom  14
Affiliations
Randomized Controlled Trial

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 et al. Am J Kidney Dis. 2017 Sep.

Abstract

Background: Mild 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 design: Cohort study.

Setting & participants: The 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.

Predictor: Serum phosphorus levels were determined in 3,138 FAVORIT trial participants at randomization.

Results: During 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).

Limitations: We lacked data for concentrations of parathyroid hormone, fibroblast growth factor 23, or vitamin D metabolites.

Conclusions: Serum 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.

Keywords: Renal transplantation; cardiovascular disease (CVD); chronic kidney disease (CKD); death; graft failure; hyperphosphatemia; kidney failure; kidney transplant recipient (KTR); phosphate toxicity; serum phosphorus.

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Conflict of interest statement

Financial Disclosure: The authors declare that they have no other relevant financial interests.

In line with AJKD’s procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal policies, an Acting Editor-in-Chief (Associate Editor Peter P. Reese, MD, MSCE) handled the peer-review and decision-making processes.

Figures

Figure 1
Figure 1
Derivation of phosphorus analysis cohort. *Phosphorus cohort– eligible Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) participants were the 3,530 who were not missing baseline creatinine, estimated glomerular filtration rate, cholesterol, triglyceride, or follow-up values and who had urine sent for determination of albumin-creatinine ratio. Abbreviations: BMI, body mass index; CVD, cardiovascular disease; SBP, systolic blood pressure.
See this image and copyright information in PMC

References

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