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Effects of Intensive Blood Pressure Lowering on Kidney Tubule Injury in CKD: A Longitudinal Subgroup Analysis in SPRINT
Open accessAbstract
Background Random assignment to the intensive systolic blood pressure (SBP) arm (<120 mm Hg) in the Systolic Blood Pressure Intervention Trial (SPRINT) resulted in more rapid declines in estimated glomerular filtration rates (eGFRs) than in the standard arm (SBP < 140 mm Hg). Whether this change reflects hemodynamic effects or accelerated intrinsic kidney damage is unknown. Study Design Longitudinal subgroup analysis of clinical trial participants. Settings & Participants Random sample of SPRINT participants with prevalent chronic kidney disease (CKD) defined as eGFR < 60 mL/min/1.73 m2 by the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation at baseline. Outcomes & Measurements Urine biomarkers of tubule function (β2-microglobulin [B2M], α1-microglobulin [A1M]), and uromodulin), injury (interleukin 18, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin), inflammation (monocyte chemoattractant protein 1), and repair (human cartilage glycoprotein 40) at baseline, year 1, and year 4. Biomarkers were indexed to urine creatinine concentration and changes between arms were evaluated using mixed-effects linear models and an intention-to-treat approach. Results 978 SPRINT participants (519 in the intensive and 459 in the standard arm) with prevalent CKD were included. Mean age was 72 ± 9 years and eGFR was 46.1 ± 9.4 mL/min/1.73 m2 at baseline. Clinical characteristics, eGFR, urinary albumin-creatinine ratio, and all 8 biomarker values were similar across arms at baseline. Compared to the standard arm, eGFR was lower by 2.9 and 3.3 mL/min/1.73 m2 in the intensive arm at year 1 and year 4. None of the 8 tubule marker levels was higher in the intensive arm compared to the standard arm at year 1 or year 4. Two tubule function markers (B2M and A1M) were 29% (95% CI, 10%−43%) and 24% (95% CI, 10%−36%) lower at year 1 in the intensive versus standard arm, respectively. Limitations Exclusion of persons with diabetes, and few participants had advanced CKD. Conclusions Among participants with CKD in SPRINT, random assignment to the intensive SBP arm did not increase any levels of 8 urine biomarkers of tubule cell damage despite loss of eGFR. These findings support the hypothesis that eGFR declines in the intensive arm of SPRINT predominantly reflect hemodynamic changes rather than intrinsic damage to kidney tubule cells.
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“Moreover, a measure of markers for AKI showed no significant increase of any markers with increased creatinine (37).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [37]
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“An analysis of the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD BP) trial demonstrated that participants randomized to intensive blood pressure lowering with up to a 30% increase in serum creatinine did not have any increase in mortality or progressive kidney disease (36,37).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [37]
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“An analysis of the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD BP) trial demonstrated that participants randomized to intensive blood pressure lowering with up to a 30% increase in serum creatinine did not have any increase in mortality or progressive kidney disease (36,37).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [37]
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Metadata
- Authors
- Malhotra, R., Craven, T., Ambrosius, W. T., Killeen, A. A., Haley, W. E., Cheung, A. K., Chonchol, M., Sarnak, M., Parikh, C. R., Shlipak, M. G., & Ix, J. H.
- Affiliations
- University of California San Diego (US)
- Wake Forest University Health Sciences (US)
- University of Minnesota (US)
- Mayo Clinic in Florida (US)
- University of Utah (US)
- University of Colorado Denver (US)
- Tufts Medical Center (US)
- Yale University (US)
- San Francisco VA Medical Center (US)
- Corresponding author
- Ix, Joachim H.
- ORCID
- Venue
- American Journal of Kidney Diseases
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 73
- Issue
- 1
- Pages
- 21-30
- ISSN
- 0272-6386 (ISSN-L)
- PMC
- PMC7325694
- OpenAlex
- W2895157652
- Semantic Scholar
- 7d67f77b1830c29b36fa820e21fb195dbdb9ff18
- Cited by
- 132
- References
- 33
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 12 · 2023: 15 · 2022: 11 · 2021: 17 · 2020: 30 · 2019: 18
- FWCI
- 14.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Kidney Diseases (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK098234, K24DK110427)
- American Heart Association (14EIA18560026)
- NIH (HHSN268200900040C)
- National Heart, Lung, and Blood Institute (HHSN268200900046C)
- NIDDK (HHSN268200900047C)
- National Institute on Aging (HHSN268200900048C)
- National Institute of Neurological Disorders and Stroke (HHSN268200900049C)
- National Center for Advancing Translational Sciences of the NIH (UL1TR000439, UL1RR025755, UL1RR024134, UL1TR000003, UL1RR025771, UL1TR000093, UL1RR025752, UL1TR000073, UL1TR001064, UL1TR000050, UL1TR000005, 9U54TR000017-06, UL1TR000105-05, UL1TR000445, UL1TR000075, UL1TR000002, UL1TR000064, UL1TR000433, P30GM103337)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- intensive blood pressure lowering, chronic kidney disease, SPRINT trial, estimated glomerular filtration rate decline, urinary biomarkers, beta2-microglobulin, alpha1-microglobulin, uromodulin, KIM-1, neutrophil gelatinase-associated lipocalin, IL-18, MCP-1, renal inflammation, kidney repair, hemodynamic effects
- MeSH terms
- Aged, Aged, 80 and over, Female, Glomerular Filtration Rate, Humans, Hypertension, Kidney Tubules, Male, Middle Aged, Biomarkers, Renal Insufficiency, Chronic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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