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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Disclosures: Dr. Beddhu reports grants from Bayer and Ab-bVie 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, Gen-zyme, 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/ConflictOfInterest Forms.do?msNum=M16-2966.
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, HHSN268200 900048C, 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: P30GM10 3337 (National Institute of General Medical Sciences Centers of Biomedical Research Excellence Award).