PTH, FGF23, and intensive blood pressure lowering in chronic kidney disease participants in SPRINT

SPRINT Research Group

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6 Scopus citations

Abstract

Background and objectives The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that intensive BP lowering reduced the risk of cardiovascular disease, but increased eGFR decline. Serum parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) concentrations are elevated in CKD and are associated with cardiovascular disease. We evaluated whether intact PTH or intact FGF23 concentrations modify the effects of intensive BP control on cardiovascular events, heart failure, and all-cause mortality in SPRINT participants with CKD. Design, setting, participants, & measurements We measured PTH and FGF23 in 2486 SPRINT participants with eGFR<60 ml/min per 1.73 m 2 at baseline. Cox models were used to evaluate whether serum PTH and FGF23 concentrations were associated with cardiovascular events, heart failure, and all-cause mortality, and whether PTH and FGF23 modified the effects of intensive BP control. Results The mean age of this subcohort was 73 years, 60% were men, and mean eGFR was 46±11 ml/min per 1.73 m 2 . Median PTH was 48 (interquartile range [IQR], 35–67) pg/ml and FGF23 was 66 (IQR, 52–88) pg/ml. There were 261 composite cardiovascular events, 102 heart failure events, and 179 deaths within the subcohort. The adjusted hazard ratio (HR) per doubling of PTH concentration for cardiovascular events, heart failure, and all-cause mortality were 1.29 (95% confidence interval [95% CI], 1.06 to 1.57), 1.32 (95% CI, 0.96 to 1.83), and 1.04 (95% CI, 0.82 to 1.31), respectively. There were significant interactions between PTH and BP arm for both the cardiovascular (P-interaction=0.01) and heart failure (P-interaction=0.004) end points. Participants with a PTH above the median experienced attenuated benefits of intensive BP control on cardiovascular events (adjusted HR, 1.02; 95% CI, 0.72 to 1.42) compared with participants with a PTH below the median (adjusted HR, 0.67; 95% CI, 0.45 to 1.00). FGF23 was not independently associated with any outcome and did not modify the effects of the intervention. Conclusions SPRINT participants with CKD and a high serum PTH received less cardiovascular protection from intensive BP therapy than participants with a lower serum PTH.

Original languageEnglish (US)
Pages (from-to)1816-1824
Number of pages9
JournalClinical Journal of the American Society of Nephrology
Volume13
Issue number12
DOIs
StatePublished - Dec 7 2018

Bibliographical note

Funding Information:
The Systolic Blood Pressure Intervention Trial (SPRINT) investigators acknowledge the contribution of study medications (azil-sartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. All components of the SPRINT study protocol were designed and implemented by the investigators. The investigative team collected, analyzed, and interpreted the data. All aspects of manuscript writing and revision were carried out by the coauthors. This work was supported by the National Institutes of Health (NIH) and the National Research Service Award through the National In-stitutes of Diabetes and Digestive and Kidney Diseases (NIDDK;grants RO1DK098234 and K24DK110427 to J.H.I. and T32DK104717 and F32DK116476 to C.G.), the NIH Loan Repayment Program to C.G., the American Society of Nephrology Ben J. Lipps Research Fellowship Program award to C.G., and the American Heart Association (grant 14EIA18560026toJ.H.I.).SPRINT is funded with federal funds from the NIH, including the National Heart, Lung, and Blood Institute, the NIDDK, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke (contracts HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C, and interagency agreement A-HL-13-002-001). It was also supported in part with resources and use of facilities through the Department of Veterans Affairs. We also acknowledge the support from the following Clinical and Translation Science Awards funded by National Center for Advancing Translational Sciences: Case Western Reserve University: UL1TR000439; Ohio State University: UL1RR025755; University of Pennsylvania: UL1RR024134 and UL1TR000003; Boston University: UL1RR025771; Stanford University: UL1TR000093; Tufts University: UL1RR025752, UL1TR000073, and UL1TR001064; University of Illinois: UL1TR000050; University of Pittsburgh: UL1TR000005; University of Texas, Southwestern: 9U54TR000017-06; University of Utah: UL1TR000105-05; Vanderbilt University: UL1 TR000445; George Washington University: UL1TR000075; University of CA, Davis: UL1 TR000002; University of Florida: UL1 TR000064; University of Michigan:UL1TR000433;TulaneUniversity: P30GM103337Centers of Biomedical Research Excellence Award National Institute of General Medical Sciences; and Wake Forest University: UL1TR001420. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of Veterans Affairs, or the US Government. For a full list of contributors to SPRINT, please see the supplementary acknowledgment list: https://www.nejm.org/doi/suppl/10.1056/NEJMoa1511939/suppl_file/nejmoa1511939_ appendix.pdf. Because M.B.C. is a Deputy Editor of the Clinical Journal of the American Society of Nephrology, he was not involved in the peer review process for this manuscript. Another editor oversaw the peer review and decision-making process for this manuscript.

Publisher Copyright:
© 2018 by the American Society of Nephrology.

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