American Journal of Kidney Diseases

Effects of Intensive Blood Pressure Lowering on Kidney Tubule Injury in CKD: A Longitudinal Subgroup Analysis in SPRINT

Published:October 02, 2018DOI:


      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.


      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.


      Exclusion of persons with diabetes, and few participants had advanced CKD.


      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.

      Graphical Abstract

      Index Words

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      Linked Article

      • Estimated GFR Decline and Tubular Injury Biomarkers With Intensive Blood Pressure Control
        American Journal of Kidney DiseasesVol. 73Issue 1
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          Current clinical practice guidelines recommend a blood pressure (BP) target of 130/80 mm Hg in those with and without chronic kidney disease (CKD) to reduce morbidity and mortality.1 These guidelines are supported by recent evidence from clinical trials, including the Systolic Blood Pressure Intervention Trial (SPRINT), which showed reduced cardiovascular events and all-cause mortality with more intensive systolic BP (SBP) control in this high-risk population.2 Commendably, the investigators thoroughly investigated and reported adverse effects associated with intense BP control.
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