Background:
The public health significance of the reported higher incidence of chronic kidney disease (CKD) with intensive systolic blood pressure (SBP) lowering is unclear.
Objective:
To examine the effects of intensive SBP lowering on kidney and cardiovascular outcomes and contrast its apparent beneficial and adverse effects.
Design:
Subgroup analyses of SPRINT (Systolic Blood Pressure Intervention Trial). (ClinicalTrials.gov: NCT01206062)
Setting:
Adults with high blood pressure and elevated cardiovascular risk.
Participants:
6662 participants with a baseline estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2.
Intervention:
Random assignment to an intensive or standard SBP goal (120 or 140 mm Hg, respectively).
Measurements:
Differences in mean eGFR during follow-up (estimated with a linear mixed-effects model), prespecified incident CKD (defined as a >30% decrease in eGFR to a value <60 mL/min/1.73 m2), and a composite of all-cause death or cardiovascular event, with surveillance every 3 months.
Results:
The difference in adjusted mean eGFR between the intensive and standard groups was −3.32 mL/min/1.73 m2 (95% CI, −3.90 to −2.74 mL/min/1.73 m2) at 6 months, was −4.50 mL/min/1.73 m2 (CI, −5.16 to −3.85 mL/min/1.73 m2) at 18 months, and remained relatively stable thereafter. An incident CKD event occurred in 3.7% of participants in the intensive group and 1.0% in the standard group at 3-year follow-up, with a hazard ratio of 3.54 (CI, 2.50 to 5.02). The corresponding percentages for the composite of death or cardiovascular event were 4.9% and 7.1% at 3-year follow-up, with a hazard ratio of 0.71 (CI, 0.59 to 0.86).
Limitation:
Long-term data were lacking.
Conclusion:
Intensive SBP lowering increased risk for incident CKD events, but this was outweighed by cardiovascular and all-cause mortality benefits.
Primary Funding Source:
National Institutes of Health.
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Author, Article and Disclosure Information
From University of Utah School of Medicine, Salt Lake City, Utah; Wake Forest School of Medicine, Winston-Salem, North Carolina; University of Texas Southwestern Medical Center, Dallas, Texas; Ohio State University, Columbus, Ohio; University of Pennsylvania, Philadelphia, Pennsylvania; University of Minnesota, Minneapolis, Minnesota; National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; University of Illinois at Chicago, Chicago, Illinois;
VA Medical Center, Washington, DC; Case Western Reserve University, Cleveland, Ohio; University of California, Los Angeles, Los Angeles, California; VA Medical Center, Albuquerque, New Mexico; VA Medical Center, Memphis, Tennessee; and Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.
Note: All components of the SPRINT study protocol were designed and implemented by the investigators. The investigative team collected, analyzed, and interpreted the data. All manuscript writing and revising were done by the authors.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the U.S. Department of Veterans Affairs, or the U.S. government.
Acknowledgment: The SPRINT investigators thank Takeda Pharmaceuticals International for contributing study medications (azilsartan and azilsartan–chlorthalidone).
Financial Support: SPRINT received federal funds from the National Institutes of Health, including the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute on Aging; and the National Institute of Neurological Disorders and Stroke, under contract numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and interagency agreement number A-HL-13-002-001. It was also supported in part with resources and use of facilities through the U.S. Department of Veterans Affairs. Additional support was provided by the following Clinical and Translational Science Awards funded by the 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 Medical Center: 9U54TR000017-06; University of Utah: UL1TR000105-05; Vanderbilt University: UL1 TR000445; George Washington University: UL1TR000075; University of California, Davis: UL1 TR000002; University of Florida: UL1 TR000064; University of Michigan: UL1TR000433; and Tulane University: P30GM103337 (National Institute of General Medical Sciences Centers of Biomedical Research Excellence Award).
Disclosures: Dr. Beddhu reports grants from Bayer and AbbVie outside the submitted work. Dr. Toto reports other support from Amgen, Boehringer Ingelheim, Reata Pharmaceuticals, Novo Nordisk, Bayer Pharmaceuticals, and AstraZeneca outside the submitted work. Dr. Greene reports personal fees from Janssen Pharmaceuticals and Pfizer outside the submitted work. Dr. Freedman reports a grant from Novartis Pharmaceuticals and personal fees from Ionis Pharmaceuticals and AstraZeneca outside the submitted work. Dr. Killeen reports personal fees from Roche Diagnostics outside the submitted work. Dr. Rahman reports a grant from Bayer outside the submitted work. Dr. Rastogi reports grants from Cubist, Relypsa, Sanofi, Kadmon, AMAG, Amgen, AstraZeneca, Bayer, Genzyme, GlaxoSmithKline, Omeros, Otsuka, Overture, Questcor, Sandoz, VPI, and SPRINT; personal fees from Cubist, Fresenius Medical Care, Medscape, Relypsa, and Sanofi; nonfinancial support from Relypsa, AstraZeneca, and Bayer; and other support from Fresenius Medical Care, Kadmon, and Janssen outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-2966.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: See the Supplement. Statistical code: Not available. Data set: Partially available at https://biolincc.nhlbi.nih.gov/studies/sprint_pop.
Corresponding Author: Srinivasan Beddhu, MD, Division of Nephrology & Hypertension, University of Utah School of Medicine, 295 Chipeta Way, Suite 4000, Salt Lake City, UT 84108; e-mail, Srinivasan.
Current Author Addresses: Drs. Beddhu, Greene, and Cheung: Division of Nephrology & Hypertension, University of Utah School of Medicine, 295 Chipeta Way, Suite 4000, Salt Lake City, UT 84108.
Drs. Rocco, Freedman, and Hawfield: Section on Nephrology, Wake Forest School of Medicine, 1 Medical Center Boulevard, Winston-Salem, NC 27157-1053.
Dr. Toto: Professor of Medicine, Associate Dean for Clinical and Translational Research, University of Texas Southwestern Medical Center, 5623 Harry Hines Boulevard, Dallas, TX 75390-8592.
Mr. Craven: Senior Biostatistician, Department of Biostatistical Sciences, Wake Forest School of Medicine, 1 Medical Center Boulevard, Winston-Salem, NC 27157-1063.
Dr. Bhatt: Ohio State University, Ground Floor, 395 West 12th Avenue, Columbus, OH 43210.
Dr. Cohen: Renal, Electrolyte and Hypertension Division, University of Pennsylvania, 1 Founders Building, 3400 Spruce Street, Philadelphia, PA 19104.
Dr. Killeen: Professor and Vice-Chair for Clinical Affairs, Department of Laboratory Medicine & Pathology, University of Minnesota, 420 Delaware Street SE, MMC 609, Minneapolis, MN 55455.
Dr. Kimmel: Senior Advisor, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 6707 Democracy Boulevard, Bethesda, MD 20892.
Dr. Lash: Division of Nephrology, University of Illinois at Chicago, 820 South Wood Street (M/C 793), Chicago, IL 60612-7315.
Dr. Papademetriou: VA Medical Center, 50 Irving Street NW, Room 1D137, Washington, DC 20422.
Dr. Rahman: Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44196.
Dr. Rastogi: Division of Nephrology, University of California, Los Angeles, 10630 Santa Monica Boulevard, Los Angeles, CA 90025-4837.
Dr. Servilla: New Mexico Veterans Administration Health Care System, Medicine Service, Renal Section, 120 San Pedro SE, Albuquerque, NM 87108.
Dr. Townsend: Nephrology & Hypertension, University of Pennsylvania, 122 Founders Building, 3400 Spruce Street, Philadelphia, PA 19104.
Dr. Wall: Section 111b, Division of Nephrology, VA Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104.
Dr. Whelton: Department of Epidemiology #8318, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street, Room 2018, New Orleans, LA 70112.
Author Contributions: Conception and design: S. Beddhu, M.V. Rocco, A.K. Cheung, P.L. Kimmel, J. Lash, M. Rahman, A. Rastogi, P.K. Whelton.
Analysis and interpretation of the data: S. Beddhu, R. Toto, T.E. Craven, T. Greene, A.K. Cheung, B.I. Freedman, A.T. Hawfield, P.L. Kimmel, J. Lash, V. Papademetriou, M. Rahman, A. Rastogi, R.R. Townsend, B. Wall, P.K. Whelton.
Drafting of the article: S. Beddhu, M.V. Rocco, T.E. Craven, U. Bhatt, B.I. Freedman, A.A. Killeen, P.L. Kimmel, J. Lash, K. Servilla, P.K. Whelton.
Critical revision of the article for important intellectual content: S. Beddhu, M.V. Rocco, R. Toto, T. Greene, U. Bhatt, A.K. Cheung, D. Cohen, B.I. Freedman, A.T. Hawfield, P.L. Kimmel, J. Lash, V. Papademetriou, M. Rahman, A. Rastogi, K. Servilla, R.R. Townsend, P.K. Whelton.
Final approval of the article: S. Beddhu, M.V. Rocco, R. Toto, T.E. Craven, T. Greene, U. Bhatt, A.K. Cheung, D. Cohen, B.I. Freedman, A.T. Hawfield, A.A. Killeen, P.L. Kimmel, J. Lash, V. Papademetriou, M. Rahman, A. Rastogi, K. Servilla, R.R. Townsend, B. Wall, P.K. Whelton.
Provision of study materials or patients: S. Beddhu, M.V. Rocco, A.K. Cheung, J. Lash, M. Rahman, A. Rastogi, K. Servilla, R.R. Townsend, B. Wall.
Statistical expertise: T.E. Craven, T. Greene, P.K. Whelton.
Obtaining of funding: S. Beddhu, A.K. Cheung, B.I. Freedman, J. Lash.
Administrative, technical, or logistic support: S. Beddhu, A.K. Cheung, A.A. Killeen, M. Rahman.
Collection and assembly of data: S. Beddhu, U. Bhatt, A.K. Cheung, B.I. Freedman, A.A. Killeen, J. Lash, V. Papademetriou, M. Rahman, A. Rastogi, R.R. Townsend.
This article was published at Annals.org on 5 September 2017.
* For a list of members of the SPRINT Research Group, see Appendix 1.
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