Effect of Intensive Blood Pressure Lowering on Kidney Tubule Injury: Findings From the ACCORD Trial Study Participants

Girish N. Nadkarni, Kinsuk Chauhan, Veena Rao, Joachim H. Ix, Michael G. Shlipak, Chirag Parikh, Steven G. Coca

Research output: Contribution to journalArticle

Abstract

Rationale & Objective: Random assignment to intensive blood pressure (BP) lowering (systolic BP < 120 mm Hg) compared to a less intensive BP target (systolic BP < 140 mm Hg) in the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD-BP) trial resulted in a more rapid decline in estimated glomerular filtration rate (eGFR). Whether this reflects hemodynamic effects or intrinsic kidney damage is unknown. Study Design: Longitudinal analysis of a subgroup of clinical trial participants. Settings & Participants: A subgroup of 529 participants in ACCORD-BP. Exposures: Urine biomarkers of tubular injury (kidney injury molecule 1, interleukin 18 [IL-18]), repair (human cartilage glycoprotein 39 [YKL-40]), and inflammation (monocyte chemoattractant protein 1) at baseline and year 2. Outcomes: Changes in eGFR from baseline to 2 years. Analytical Approach: We compared changes in biomarker levels and eGFRs across participants treated to an intensive versus less intensive BP goal using analysis of covariance. Results: Of 529 participants, 260 had been randomly assigned to the intensive and 269 to the standard BP arm. Mean age was 62 ± 6.5 years and eGFR was 90 mL/min/1.73 m2. Baseline clinical characteristics, eGFRs, urinary albumin-creatinine ratios (ACRs), and urinary biomarker levels were similar across BP treatment groups. Compared to less intensive BP treatment, eGFR was 9.2 mL/min/1.73 m2 lower in the intensive BP treatment group at year 2. Despite the eGFR reduction, within this treatment group, ACR was 30% lower and 4 urinary biomarker levels were unchanged or lower at year 2. Also within this group, participants with the largest declines in eGFRs had greater reductions in urinary IL-18 and YKL-40 levels. In a subgroup analysis of participants developing incident chronic kidney disease (sustained 30% decline and eGFR < 60 mL/min/1.73 m2; n = 77), neither ACR nor 4 biomarker levels increased in the intensive treatment group, whereas the level of 1 biomarker, IL-18, increased in the less intensive treatment group. Limitations: Few participants with advanced baseline chronic kidney disease. Comparisons across treatment groups do not represent comparisons of treatment arms created solely through randomization. Conclusions: Among a subset of ACCORD-BP trial participants, intensive BP control was associated with reductions in eGFRs, but not with an increase in injury marker levels. These findings support that eGFR decline observed with intensive BP goals in ACCORD participants may predominantly reflect hemodynamic alterations.

Original languageEnglish (US)
Pages (from-to)31-38
Number of pages8
JournalAmerican Journal of Kidney Diseases
Volume73
Issue number1
DOIs
StatePublished - Jan 1 2019

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Kidney Tubules
Blood Pressure
Wounds and Injuries
Glomerular Filtration Rate
Biomarkers
Interleukin-18
Albumins
Creatinine
Chronic Renal Insufficiency
Hemodynamics
Kidney
Chemokine CCL2
Random Allocation

Keywords

  • blood pressure (BP)
  • Chronic kidney disease (CKD)
  • CKD progression
  • eGFR decline
  • estimated glomerular filtration rate (eGFR)
  • hemodynamics
  • hypertension
  • intensive BP control
  • kidney tubule
  • renal perfusion
  • tubular injury
  • urinary biomarkers
  • urine

ASJC Scopus subject areas

  • Nephrology

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Effect of Intensive Blood Pressure Lowering on Kidney Tubule Injury : Findings From the ACCORD Trial Study Participants. / Nadkarni, Girish N.; Chauhan, Kinsuk; Rao, Veena; Ix, Joachim H.; Shlipak, Michael G.; Parikh, Chirag; Coca, Steven G.

In: American Journal of Kidney Diseases, Vol. 73, No. 1, 01.01.2019, p. 31-38.

Research output: Contribution to journalArticle

Nadkarni, Girish N. ; Chauhan, Kinsuk ; Rao, Veena ; Ix, Joachim H. ; Shlipak, Michael G. ; Parikh, Chirag ; Coca, Steven G. / Effect of Intensive Blood Pressure Lowering on Kidney Tubule Injury : Findings From the ACCORD Trial Study Participants. In: American Journal of Kidney Diseases. 2019 ; Vol. 73, No. 1. pp. 31-38.
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AU - Nadkarni, Girish N.

AU - Chauhan, Kinsuk

AU - Rao, Veena

AU - Ix, Joachim H.

AU - Shlipak, Michael G.

AU - Parikh, Chirag

AU - Coca, Steven G.

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N2 - Rationale & Objective: Random assignment to intensive blood pressure (BP) lowering (systolic BP < 120 mm Hg) compared to a less intensive BP target (systolic BP < 140 mm Hg) in the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD-BP) trial resulted in a more rapid decline in estimated glomerular filtration rate (eGFR). Whether this reflects hemodynamic effects or intrinsic kidney damage is unknown. Study Design: Longitudinal analysis of a subgroup of clinical trial participants. Settings & Participants: A subgroup of 529 participants in ACCORD-BP. Exposures: Urine biomarkers of tubular injury (kidney injury molecule 1, interleukin 18 [IL-18]), repair (human cartilage glycoprotein 39 [YKL-40]), and inflammation (monocyte chemoattractant protein 1) at baseline and year 2. Outcomes: Changes in eGFR from baseline to 2 years. Analytical Approach: We compared changes in biomarker levels and eGFRs across participants treated to an intensive versus less intensive BP goal using analysis of covariance. Results: Of 529 participants, 260 had been randomly assigned to the intensive and 269 to the standard BP arm. Mean age was 62 ± 6.5 years and eGFR was 90 mL/min/1.73 m2. Baseline clinical characteristics, eGFRs, urinary albumin-creatinine ratios (ACRs), and urinary biomarker levels were similar across BP treatment groups. Compared to less intensive BP treatment, eGFR was 9.2 mL/min/1.73 m2 lower in the intensive BP treatment group at year 2. Despite the eGFR reduction, within this treatment group, ACR was 30% lower and 4 urinary biomarker levels were unchanged or lower at year 2. Also within this group, participants with the largest declines in eGFRs had greater reductions in urinary IL-18 and YKL-40 levels. In a subgroup analysis of participants developing incident chronic kidney disease (sustained 30% decline and eGFR < 60 mL/min/1.73 m2; n = 77), neither ACR nor 4 biomarker levels increased in the intensive treatment group, whereas the level of 1 biomarker, IL-18, increased in the less intensive treatment group. Limitations: Few participants with advanced baseline chronic kidney disease. Comparisons across treatment groups do not represent comparisons of treatment arms created solely through randomization. Conclusions: Among a subset of ACCORD-BP trial participants, intensive BP control was associated with reductions in eGFRs, but not with an increase in injury marker levels. These findings support that eGFR decline observed with intensive BP goals in ACCORD participants may predominantly reflect hemodynamic alterations.

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KW - hemodynamics

KW - hypertension

KW - intensive BP control

KW - kidney tubule

KW - renal perfusion

KW - tubular injury

KW - urinary biomarkers

KW - urine

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