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PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT.

Authors
  • Ginsberg, Charles1, 2
  • Craven, Timothy E3
  • Chonchol, Michel B4
  • Cheung, Alfred K5
  • Sarnak, Mark J6
  • Ambrosius, Walter T3
  • Killeen, Anthony A7
  • Raphael, Kalani L5
  • Bhatt, Udayan Y8
  • Chen, Jing9
  • Chertow, Glenn M10
  • Freedman, Barry I11
  • Oparil, Suzanne12
  • Papademetriou, Vasilios13
  • Wall, Barry M14
  • Wright, Clinton B15
  • Ix, Joachim H16, 2
  • Shlipak, Michael G17, 18
  • 1 Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California; [email protected]
  • 2 Division of Nephrology-Hypertension, University of California, San Diego, San Diego, California.
  • 3 Department of Biostatistical Sciences and.
  • 4 Division of Renal Diseases and Hypertension, University of Anschutz Medical Center, Aurora, Colorado.
  • 5 Division of Nephrology and Hypertension, University of Utah, Salt Lake City, Utah.
  • 6 Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts.
  • 7 Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.
  • 8 Division of Nephrology, The Ohio State University, Wexner Medical Center, Columbus, Ohio.
  • 9 Nephrology and Hypertension Section, Tulane University School of Medicine, New Orleans, Louisiana.
  • 10 Division of Nephrology, Stanford University School of Medicine, Palo Alto, California.
  • 11 Nephrology Section, Wake Forest School of Medicine, Winston-Salem, North Carolina.
  • 12 Division of Cardiovascular Disease, University of Alabama School of Medicine, Birmingham, Alabama.
  • 13 Division of Cardiology, Georgetown University Medical Center, Washington, DC.
  • 14 Division of Nephrology, Veterans Affairs Medical Center, Memphis, Tennessee.
  • 15 Department of Neurology, University of Miami, Miami, Florida.
  • 16 Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California.
  • 17 Kidney Health Research Collaborative, Veterans Affairs Medical Center, San Francisco, California; and.
  • 18 Department of Medicine, University of California, San Francisco, San Francisco, California.
Type
Published Article
Journal
Clinical Journal of the American Society of Nephrology
Publisher
American Society of Nephrology
Publication Date
Dec 07, 2018
Volume
13
Issue
12
Pages
1816–1824
Identifiers
DOI: 10.2215/CJN.05390518
PMID: 30425104
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. We measured PTH and FGF23 in 2486 SPRINT participants with eGFR<60 ml/min per 1.73 m2 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. The mean age of this subcohort was 73 years, 60% were men, and mean eGFR was 46±11 ml/min per 1.73 m2. 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. SPRINT participants with CKD and a high serum PTH received less cardiovascular protection from intensive BP therapy than participants with a lower serum PTH. Copyright © 2018 by the American Society of Nephrology.

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