Low Achieved Systolic Blood Pressure Related to Kidney Protection in Diabetic and Non-Diabetic High-Risk Hypertensive Patients

Am J Hypertens. 2025 Nov 17;38(12):1106-1119. doi: 10.1093/ajh/hpaf093.

Abstract

Background: Protecting the kidneys by lowering systolic blood pressure (SBP) in hypertensive patients is not unequivocally settled. We tested the hypothesis that achieving lower average SBP in middle-aged and older high-risk hypertensive patients with and without type-2 diabetes mellitus through several years would clarify kidney protection.

Methods: We analyzed patients 50-80 years with no cardiovascular events during the first 6 months of drug up-titration after randomization to valsartan or amlodipine, and with 3 or more visits onwards with standardized BP measurements. Adjusted Cox analyzes compared worsened kidney function defined as a 50% rise in se-creatinine on a minimum of two occasions at least 4 weeks apart or end-stage kidney disease (ESKD) in achieved SBP quartiles and in patients who achieved SBP < 130 and 130-139 mmHg with patients whose SBP remained ≥140 mmHg.

Results: A total of 13,803 patients were investigated of whom 4,655 had DM. Patients with DM had less worsened kidney function at SBP 130-139 mmHg (HR = 0.524, 95% CIs 0.375-0.733, n = 1849, P < 0.001) and at SBP < 130 mmHg (HR = 0.538, CIs 0.316-0.915, n = 674, P = 0.022) compared with patients at ≥ 140 mmHg. They also had less ESKD at SBP 130-139 mmHg (HR = 0.442, CIs 0.196-1.000, P = 0.050) with a similar trend at SBP < 130 mmHg and in quartile analysis with only 1 ESKD in the lowest quartile. Findings in patients without DM (n = 9,148) were similar to DM.

Conclusions: In high-risk hypertensive patients aged 50-80 years, with and without DM, targeting SBP of 130-139 mmHg confers kidney protection with possible further benefit at the lower target of SBP < 130 mmHg.

Clinical trials registration: Trial Number NCT06395194, www.clinicaltrials.gov.

Keywords: blood pressure; chronic kidney disease; creatinine; end-stage kidney disease; hypertension; kidney function; the VALUE Trial.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amlodipine* / therapeutic use
  • Antihypertensive Agents* / therapeutic use
  • Blood Pressure* / drug effects
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / diagnosis
  • Diabetes Mellitus, Type 2* / physiopathology
  • Female
  • Humans
  • Hypertension* / complications
  • Hypertension* / diagnosis
  • Hypertension* / drug therapy
  • Hypertension* / physiopathology
  • Kidney Failure, Chronic* / etiology
  • Kidney Failure, Chronic* / physiopathology
  • Kidney Failure, Chronic* / prevention & control
  • Kidney* / drug effects
  • Kidney* / physiopathology
  • Male
  • Middle Aged
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Valsartan / therapeutic use

Substances

  • Amlodipine
  • Antihypertensive Agents
  • Valsartan

Associated data

  • ClinicalTrials.gov/NCT06395194