Srinivasan Beddhu1, Tom Greene2, Robert Boucher3, William C Cushman4, Guo Wei5, Gregory Stoddard2, Joachim H Ix6, Michel Chonchol7, Holly Kramer8, Alfred K Cheung9, Paul L Kimmel10, Paul K Whelton11, Glenn M Chertow12. 1. Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, UT, USA; Division of Nephrology and Hypertension, University of Utah School of Medicine, Salt Lake City, UT, USA. Electronic address: srinivasan.beddhu@hsc.utah.edu. 2. Division of Biostatistics, University of Utah School of Medicine, Salt Lake City, UT, USA. 3. Division of Nephrology and Hypertension, University of Utah School of Medicine, Salt Lake City, UT, USA. 4. Medical Service, Veterans Affairs Medical Center, Memphis, TN, USA. 5. Division of Nephrology and Hypertension, University of Utah School of Medicine, Salt Lake City, UT, USA; Division of Biostatistics, University of Utah School of Medicine, Salt Lake City, UT, USA. 6. Department of Medicine, University of California, San Diego, CA, USA. 7. Department of Medicine, University of Colorado, Denver, CO, USA. 8. Departments of Public Health Sciences and Medicine, Division of Nephrology and Hypertension, Loyola University Chicago, Maywood, IL, USA; Department of Medicine, Hines Veteran's Affairs Medical Center, Hines, IL, USA. 9. Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, UT, USA; Division of Nephrology and Hypertension, University of Utah School of Medicine, Salt Lake City, UT, USA. 10. Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD, USA. 11. School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA. 12. Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA, USA.
Abstract
BACKGROUND: Guidelines, including the 2017 American College of Cardiology and American Heart Association blood pressure guideline, recommend tighter control of systolic blood pressure in people with type 2 diabetes. However, it is unclear whether intensive lowering of systolic blood pressure increases the incidence of chronic kidney disease in this population. We aimed to compare the effects of intensive systolic blood pressure control on incident chronic kidney disease in people with and without type 2 diabetes. METHODS: The Systolic Blood Pressure Intervention Trial (SPRINT) tested the effects of a systolic blood pressure goal ofless than 120 mmHg (intensive intervention) versus a goal of less than 140 mm Hg (standard intervention) in people without diabetes. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure trial tested a similar systolic blood pressure intervention in people with type 2 diabetes. Our study is a secondary analysis of limited access datasets from SPRINT and the ACCORD trial obtained from the National Institutes of Health. In participants without chronic kidney disease at baseline (n=4311 in the ACCORD trial; n=6715 in SPRINT), we related systolic blood pressure interventions (intensive vs standard) to incident chronic kidney disease (defined as >30% decrease in estimated glomerular filtration rate [eGFR] to <60 mL/min per 1·73 m2). These trials are registered with ClinicalTrials.gov, numbers NCT01206062 (SPRINT) and NCT00000620 (ACCORD trial). FINDINGS: The average difference in systolic blood pressure between intensive and standard interventions was 13·9 mm Hg (95% CI 13·4-14·4) in the ACCORD trial and 15·2 mm Hg (14·8-15·6) in SPRINT. At 3 years, the cumulative incidence of chronic kidney disease in the ACCORD trial was 10·0% (95% CI 8·8-11·4) with the intensive intervention and 4·1% (3·3-5·1) with the standard intervention (absolute risk difference 5·9%, 95% CI 4·3-7·5). Corresponding values in SPRINT were 3·5% (95% CI 2·9-4·2) and 1·0% (0·7-1·4; absolute risk difference 2·5%, 95% CI 1·8-3·2). The absolute risk difference was significantly higher in the ACCORD trial than in SPRINT (p=0·0001 for interaction). INTERPRETATION:Intensive lowering of systolic blood pressure increased the risk of incident chronic kidney disease in people with and without type 2 diabetes. However, the absolute risk of incident chronic kidney disease was higher in people with type 2 diabetes. Our findings suggest the need for vigilance in monitoring kidney function during intensive antihypertensive drug treatment, particularly in adults with diabetes. Long-term studies are needed to understand the clinical implications of antihypertensive treatment-related reductions in eGFR. FUNDING: National Institutes of Health.
RCT Entities:
BACKGROUND: Guidelines, including the 2017 American College of Cardiology and American Heart Association blood pressure guideline, recommend tighter control of systolic blood pressure in people with type 2 diabetes. However, it is unclear whether intensive lowering of systolic blood pressure increases the incidence of chronic kidney disease in this population. We aimed to compare the effects of intensive systolic blood pressure control on incident chronic kidney disease in people with and without type 2 diabetes. METHODS: The Systolic Blood Pressure Intervention Trial (SPRINT) tested the effects of a systolic blood pressure goal of less than 120 mm Hg (intensive intervention) versus a goal of less than 140 mm Hg (standard intervention) in people without diabetes. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure trial tested a similar systolic blood pressure intervention in people with type 2 diabetes. Our study is a secondary analysis of limited access datasets from SPRINT and the ACCORD trial obtained from the National Institutes of Health. In participants without chronic kidney disease at baseline (n=4311 in the ACCORD trial; n=6715 in SPRINT), we related systolic blood pressure interventions (intensive vs standard) to incident chronic kidney disease (defined as >30% decrease in estimated glomerular filtration rate [eGFR] to <60 mL/min per 1·73 m2). These trials are registered with ClinicalTrials.gov, numbers NCT01206062 (SPRINT) and NCT00000620 (ACCORD trial). FINDINGS: The average difference in systolic blood pressure between intensive and standard interventions was 13·9 mm Hg (95% CI 13·4-14·4) in the ACCORD trial and 15·2 mm Hg (14·8-15·6) in SPRINT. At 3 years, the cumulative incidence of chronic kidney disease in the ACCORD trial was 10·0% (95% CI 8·8-11·4) with the intensive intervention and 4·1% (3·3-5·1) with the standard intervention (absolute risk difference 5·9%, 95% CI 4·3-7·5). Corresponding values in SPRINT were 3·5% (95% CI 2·9-4·2) and 1·0% (0·7-1·4; absolute risk difference 2·5%, 95% CI 1·8-3·2). The absolute risk difference was significantly higher in the ACCORD trial than in SPRINT (p=0·0001 for interaction). INTERPRETATION: Intensive lowering of systolic blood pressure increased the risk of incident chronic kidney disease in people with and without type 2 diabetes. However, the absolute risk of incident chronic kidney disease was higher in people with type 2 diabetes. Our findings suggest the need for vigilance in monitoring kidney function during intensive antihypertensive drug treatment, particularly in adults with diabetes. Long-term studies are needed to understand the clinical implications of antihypertensive treatment-related reductions in eGFR. FUNDING: National Institutes of Health.
Authors: Alexandra Barratt; Peter C Wyer; Rose Hatala; Thomas McGinn; Antonio L Dans; Sheri Keitz; Virginia Moyer; Gordon Guyatt For Journal: CMAJ Date: 2004-08-17 Impact factor: 8.262
Authors: Walter T Ambrosius; Kaycee M Sink; Capri G Foy; Dan R Berlowitz; Alfred K Cheung; William C Cushman; Lawrence J Fine; David C Goff; Karen C Johnson; Anthony A Killeen; Cora E Lewis; Suzanne Oparil; David M Reboussin; Michael V Rocco; Joni K Snyder; Jeff D Williamson; Jackson T Wright; Paul K Whelton Journal: Clin Trials Date: 2014-06-05 Impact factor: 2.486
Authors: Leo F Buckley; Dave L Dixon; George F Wohlford; Dayanjan S Wijesinghe; William L Baker; Benjamin W Van Tassell Journal: Diabetes Care Date: 2017-09-25 Impact factor: 19.112
Authors: William C Cushman; Gregory W Evans; Robert P Byington; David C Goff; Richard H Grimm; Jeffrey A Cutler; Denise G Simons-Morton; Jan N Basile; Marshall A Corson; Jeffrey L Probstfield; Lois Katz; Kevin A Peterson; William T Friedewald; John B Buse; J Thomas Bigger; Hertzel C Gerstein; Faramarz Ismail-Beigi Journal: N Engl J Med Date: 2010-03-14 Impact factor: 91.245
Authors: Tom F Brouwer; Jim T Vehmeijer; Deborah N Kalkman; Wouter R Berger; Bert-Jan H van den Born; Ron J Peters; Reinoud E Knops Journal: Diabetes Care Date: 2017-12-06 Impact factor: 19.112
Authors: Hertzel C Gerstein; Michael E Miller; Robert P Byington; David C Goff; J Thomas Bigger; John B Buse; William C Cushman; Saul Genuth; Faramarz Ismail-Beigi; Richard H Grimm; Jeffrey L Probstfield; Denise G Simons-Morton; William T Friedewald Journal: N Engl J Med Date: 2008-06-06 Impact factor: 91.245
Authors: Maryam Afkarian; Michael C Sachs; Bryan Kestenbaum; Irl B Hirsch; Katherine R Tuttle; Jonathan Himmelfarb; Ian H de Boer Journal: J Am Soc Nephrol Date: 2013-01-29 Impact factor: 10.121
Authors: Naveen Rathi; Paul K Whelton; Glenn M Chertow; William C Cushman; Alfred K Cheung; Guo Wei; Robert Boucher; Paul L Kimmel; Adam P Bress; Holly J Kramer; Catreena Al-Marji; Tom Greene; Srinivasan Beddhu Journal: Am J Hypertens Date: 2019-11-15 Impact factor: 2.689
Authors: Srinivasan Beddhu; Jincheng Shen; Alfred K Cheung; Paul L Kimmel; Glenn M Chertow; Guo Wei; Robert E Boucher; Michel Chonchol; Farid Arman; Ruth C Campbell; Gabriel Contreras; Jamie P Dwyer; Barry I Freedman; Joachim H Ix; Kent Kirchner; Vasilios Papademetriou; Roberto Pisoni; Michael V Rocco; Paul K Whelton; Tom Greene Journal: J Am Soc Nephrol Date: 2019-07-19 Impact factor: 10.121