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Randomized Controlled Trial
. 2024 Feb 1;19(2):213-223.
doi: 10.2215/CJN.0000000000000335. Epub 2023 Oct 25.

Effect of Intensive Blood Pressure Control on Kidney Outcomes: Long-Term Electronic Health Record-Based Post-Trial Follow-Up of SPRINT

Paul E Drawz  1 , Kristin M Lenoir  2 , Nayanjot Kaur Rai  1 , Anjay Rastogi  3 , Chi D Chu  4 , Frederic F Rahbari-Oskoui  5 , Paul K Whelton  6 , George Thomas  7 , Andrew McWilliams  8 , Anil K Agarwal  9 , Maritza Marie Suarez  10 , Mirela Dobre  11 , James Powell  12 , Michael V Rocco  13 , James P Lash  14 , Suzanne Oparil  15 , Dominic S Raj  16 , Jamie P Dwyer  17 , Mahboob Rahman  11 , Sandeep Soman  18 , Raymond R Townsend  19 , Priscilla Pemu  20 , Edward Horwitz  21 , Joachim H Ix  22 , Delphine S Tuot  4 , Areef Ishani  1   23 , Nicholas M Pajewski  2
Affiliations
Randomized Controlled Trial

Effect of Intensive Blood Pressure Control on Kidney Outcomes: Long-Term Electronic Health Record-Based Post-Trial Follow-Up of SPRINT

Paul E Drawz et al. Clin J Am Soc Nephrol. .

Abstract

Background: Intensive BP lowering in the Systolic Blood Pressure Intervention Trial (SPRINT) produced acute decreases in kidney function and higher risk for AKI. We evaluated the effect of intensive BP lowering on long-term changes in kidney function using trial and outpatient electronic health record (EHR) creatinine values.

Methods: SPRINT data were linked with EHR data from 49 (of 102) study sites. The primary outcome was the total slope of decline in eGFR for the intervention phase and the post-trial slope of decline during the observation phase using trial and outpatient EHR values. Secondary outcomes included a ≥30% decline in eGFR to <60 ml/min per 1.73 m 2 and a ≥50% decline in eGFR or kidney failure among participants with baseline eGFR ≥60 and <60 ml/min per 1.73 m 2 , respectively.

Results: EHR creatinine values were available for a median of 8.3 years for 3041 participants. The total slope of decline in eGFR during the intervention phase was -0.67 ml/min per 1.73 m 2 per year (95% confidence interval [CI], -0.79 to -0.56) in the standard treatment group and -0.96 ml/min per 1.73 m 2 per year (95% CI, -1.08 to -0.85) in the intensive treatment group ( P < 0.001). The slopes were not significantly different during the observation phase: -1.02 ml/min per 1.73 m 2 per year (95% CI, -1.24 to -0.81) in the standard group and -0.85 ml/min per 1.73 m 2 per year (95% CI, -1.07 to -0.64) in the intensive group. Among participants without CKD at baseline, intensive treatment was associated with higher risk of a ≥30% decline in eGFR during the intervention (hazard ratio, 3.27; 95% CI, 2.43 to 4.40), but not during the postintervention observation phase. In those with CKD at baseline, intensive treatment was associated with a higher hazard of eGFR decline only during the intervention phase (hazard ratio, 1.95; 95% CI, 1.03 to 3.70).

Conclusions: Intensive BP lowering was associated with a steeper total slope of decline in eGFR and higher risk for kidney events during the intervention phase of the trial, but not during the postintervention observation phase.

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Conflict of interest statement

A.K. Agarwal reports employment with VA Central California Health Care System; consultancy from Akebia; honoraria from Amgen; advisory or leadership role for ASDIN, Clinical Nephrology, Frontiers in Nephrology, International Journal of Nephrology, ISN, Journal of Vascular Access, KSAP, NKF, and The Open Urology & Nephrology Journal—all unpaid; and other interests or relationships with ASDIN, ASN, ISN, and NKF. C.D. Chu reports research support from Bayer Healthcare. M. Dobre reports employment with Case Western Reserve University, NIH grant funding (NHLBI HL141846), and consultancy for CareDx, Inc. (<$3,000). J.P. Dwyer reports employment with University of Utah Health; consultancy for Acuta Capital, Akebia, Applied Therapeutics, Ardelyx, AstraZeneca, Aurinia, Bayer, BI, BioRasi, BioVie, Botanix, Caladrius, Cincor, Eli Lilly, ES Therapeutics, Fibrogen, Genentech, GSK, Icon, Inversago, Ionis, Keros Therapeutics, Medpace, MicuRx, Novo Nordisk, ProKidney, PSI CRO, Rarestone, Reata, RenalytixAI, Sanofi, Tricida, ValenzaBio, and Worldwide clinical trials; ownership interest in Acelyrin, BioRasi, Inc., Innovative Renal Care, LLC, PathEx, Inc., and Venostent, Inc.; research funding from AstraZeneca and CinCor; and advisory or leadership roles for Collaborative Study Group (Board of Directors and President) and The Bolles School (Board of Trustees). E. Horwitz reports other interests or relationships as medical director for in-patient dialysis services at MetroHealth Medical Center contracted with Fresenius Kidney Care, a member of American Society of Nephrology, and a member of the International Society for Peritoneal Dialysis. J.H. Ix reports consultancy for Akebia, AstraZeneca, Bayer, Cincor, and Sanifit; research funding from Baxter International and Juvenile Diabetes Research Foundation; honoraria from Akebia, AstraZeneca, Bayer, Cincor, and Sanifit; advisory or leadership role for AlphaYoung; and other interests or relationships with Executive Board for Kidney Disease: Improving Global Outcomes. J.P. Lash reports employment with University of Illinois at Chicago and advisory or leadership role for Kidney360. A. McWilliams reports employment with Atrium Health and ownership interest in iEnroll, LLC. S. Oparil reports ownership interest in CinCor Pharma Inc.; research funding from CinCor Pharma Inc. (site PI-primary aldosterone study), George Clinical Pty (site PI-GMRx2 treatment of hypertension), Higi (site PI-BP validation study), and Mineralys (site PI-uncontrolled hypertension); patents or royalties from Elsevier; and other interests or relationships as Editor-in-Chief of Current Hypertension Reports (Springer Science Business Media LLC) until December 2023 with annual stipend of $5,000 (Springer). N.M. Pajewski reports ownership interest in Eyenovia, Longeveron, and Ocuphire Pharma. P. Pemu reports research funding from Amgen and Janssen; patents or royalties for a system and method for chronic illness care; and advisory or leadership role for American Heart Association Southeast Board (not paid). J. Powell reports employment with ECU Physicians and research funding from Idorsia as a site PI for a study done by Idorsia. J. Powell was not compensated directly. F.F. Rahbari-Oskoui reports consultancy for Otsuka and UpToDate; research funding from Duke University, Kadmon, NIH, Reata, and Sanofi/Genzyme; honoraria from Otsuka; author royalties from UpToDate; advisory or leadership roles for BMC Nephrology (Associate Editor), Journal of Cardiology and Vascular Medicine (Editorial Board member), and PKD Foundation Scientific Advisory Board Panel member; and unbranded speaker bureau for Otsuka (only raising disease awareness in ADPKD without any reference to commercial products). M. Rahman reports employment with Case Western Reserve University; research funding from Bayer Pharmaceuticals and Duke Clinical Research Institute; honoraria from Barologics for consulting for a one-time discussion and from AstraZeneca for consultant meeting; and advisory or leadership roles as an Associate Editor of CJASN and an Editorial Board member of American Journal of Nephrology. D.S. Raj reports employment with The George Washington University School of Medicine; consultancy for Novo Nordisk; research funding from NIH; honoraria from Novo Nordisk; advisory or leadership roles for NHLBI, NIDDK, and Novo Nordisk; and other interests or relationships with American Association of Kidney Patients. A. Rastogi reports consultancy for Akebia, Amicus, Ardelyx, AstraZeneca, Aurinia, Chiesi Global Inc., Chinook Therapeutics, Fresenius Medical Care-Vifor, GlaxoSmithKline, Novartis, Otsuka, Sanofi S. A., Travere Therapeutics, and Vifor Pharma Inc.; research funding from Alnylam Pharmaceuticals, AstraZeneca, Bayer, GlaxoSmithKline, Idorsia Pharmaceuticals, Ltd., Kadmon Corporation, LLC, NIH, Novo Nordisk, Omeros Inc., Palladio Biosciences, Pfizer, Protalix Biotherapeutics Ltd., Reata Pharmaceuticals, Inc., Regulus Therapeutics, Summit Therapeutics, and Sanofi; honoraria from Amgen, AstraZeneca, Aurinia, Baxter, Bayer, Fresenius Medical Care, Genzyme/Sanofi, Janssen, Natera, and Vifor Pharma Inc.; research grants and consulting fees from Amgen, AstraZeneca, Bayer, CSL Vifor, Gilead, GlaxoSmithKline, Janssen, Otsuka, Pfizer, and Sanofi; advisory or leadership roles for Akebia, Amicus, Ardelyx, AstraZeneca, Aurinia, Chiesi Global Inc., Chinook Therapeutics, Fresenius Medical Care-Vifor, GlaxoSmithKline, Novartis, Otsuka, Sanofi S. A., Travere Therapeutics, and Vifor Pharma Inc.; and speakers bureau for Amgen, AstraZeneca, Aurinia, Baxter, Bayer, Fresenius Medical Care, Genzyme/Sanofi, Natera, and Vifor Pharma Inc. M.V. Rocco reports consultancy for Bayer and George Clinical, research funding from Bayer and Boehringer Ingelheim, advisory or leadership role for National Kidney Foundation, and other interests or relationships as co-chair of International Society of Nephrology Kidney Care Network Project and as NKF KDOQI chair. S. Soman reports ownership interest in Nephroceuticals and Pfizer; advisory or leadership roles for American Medical Informatics Association, National Kidney Foundation, and National Kidney Foundation, MI; and other interests or relationships with American Medical Informatics Association, National Kidney Foundation Education Committee, and National Kidney Foundation Michigan Scientific Advisory Board. G. Thomas reports research funding from Boehringer Ingelheim and honoraria from UpToDate. R.R. Townsend reports employment with University of Pennsylvania School of Medicine; consultancy for BARD, BD, Cytel, IONIS, Janssen, Medtronic, Orchestra, and Regeneron; DSMB for Cytel and Novartis; research funding from NIH; and royalties from UpToDate. D.S. Tuot reports honoraria from Projects in Knowledge and advisory or leadership roles for BluePath Health eConsult Workgroup and National Kidney Foundation Bay Area Medical Advisory Board. P.K. Whelton reports employment with Tulane University School of Public Health and Tropical Medicine. All remaining authors have nothing to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Consolidated standards of reporting trials diagram. Cr, creatinine; EHR, electronic health record; SPRINT, Systolic Blood Pressure Intervention Trial.
Figure 2
Figure 2
Mean eGFR during long-term follow-up. Estimates and 95% CIs on the basis of generalized least squares model including trial and EHR creatinine measurements with an autoregressive correlation structure allowing variation for intraindividual and intraclinic site on the basis of days from randomization, with days from randomization modeled using nine restricted cubic splines. Date of randomization is aligned for every participant at time 0, which causes the trial and observational phases to overlap because the intervention ends at varying times with respect to randomization for each participant. CI, confidence interval.
Figure 3
Figure 3
Intensive BP lowering was not consistently associated with higher risk for decline in eGFR. Cumulative incidence of GFR decline in (A) participants without CKD (top, ≥30% decline) and in (B) participants with CKD at baseline (bottom, ≥50% decline in eGFR or kidney failure).
Figure 4
Figure 4
Agreement between SPRINT and EHR estimates of eGFR decline. Decline in eGFR was similar when evaluated using SPRINT and EHR measurements with modest differences among those randomized to intensive treatment (A) and concordance between trial and EHR estimates of total eGFR slope during the intervention phase (B). Size of dots is proportional to the number of outpatient EHR creatinine measurements.
See this image and copyright information in PMC

References

    1. Lewis CE Fine LJ Beddhu S, et al. .; SPRINT Research Group. Final report of a trial of intensive versus standard blood-pressure control. N Engl J Med. 2021;384(20):1921–1930. doi:10.1056/NEJMoa1901281 - DOI - PMC - PubMed
    1. Xie X Atkins E Lv J, et al. . Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet. 2016;387(10017):435–443. doi:10.1016/S0140-6736(15)00805-3 - DOI - PubMed
    1. Drawz PE Rai NK Lenoir KM, et al. . Effect of intensive versus standard BP control on AKI and subsequent cardiovascular outcomes and mortality: findings from the SPRINT EHR study. Kidney360. 2022;3(7):1253–1262. doi:10.34067/KID.0001572022 - DOI - PMC - PubMed
    1. Rocco MV Sink KM Lovato LC, et al. .; SPRINT Research Group. Effects of intensive blood pressure treatment on acute kidney injury events in the Systolic Blood Pressure Intervention Trial (SPRINT). Am J Kidney Dis. 2018;71(3):352–361. doi:10.1053/j.ajkd.2017.08.021 - DOI - PMC - PubMed
    1. Appel LJ Wright JT Jr. Greene T, et al. .; AASK Collaborative Research Group. Intensive blood-pressure control in hypertensive chronic kidney disease. N Engl J Med. 2010;363(10):918–929. doi:10.1056/NEJMoa0910975 - DOI - PMC - PubMed

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