Associations of Urine Biomarkers of Kidney Tubule Health With Incident Hypertension and Longitudinal Blood Pressure Change in Middle-Aged Adults: The CARDIA Study

Hypertension. 2023 Jun;80(6):1353-1362. doi: 10.1161/HYPERTENSIONAHA.123.21084. Epub 2023 Mar 29.

Abstract

Background: Urine biomarkers of kidney tubule injury associate with incident hypertension in older adults with comorbidities, but less is known about these associations in younger adults.

Methods: In 1170 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults; mean age, 45 years; 40% Black people; 56% women) without hypertension, cardiovascular disease, or kidney disease at baseline, we examined associations of urine MCP-1 (monocyte chemoattractant protein-1), α1m (alpha-1-microglobulin), KIM-1 (kidney injury molecule-1), EGF (epidermal growth factor), IL (interleukin)-18, YKL-40 (chitinase-3-like protein 1), and UMOD (uromodulin) with incident hypertension (onset of systolic blood pressure [BP] ≥130 mm Hg or diastolic BP ≥80 mm Hg or initiation of hypertension medications) and longitudinal BP change in models adjusted for hypertension risk factors, estimated glomerular filtration rate, and albuminuria.

Results: After a median 9.9 (interquartile range, 5.9-10.2) years, 376 participants developed incident hypertension. In demographic-adjusted analyses, higher tertiles of EGF associated with lower risk of incident hypertension in both Black and White participants. After multivariable adjustment, the risk of incident hypertension remained lower in tertile 2 (hazard ratio, 0.70 [95% CI, 0.50-0.97]) and tertile 3 (hazard ratio, 0.58 [0.39-0.85]) of EGF versus tertile 1. In fully adjusted models, participants in EGF tertile 3 had smaller 10-year increases in systolic (-3.4 [95% CI, -6.1 to -0.7] mm Hg) and diastolic BP (-2.6 [95% CI, -4.6 to -0.6] mm Hg) than tertile 1. Other biomarkers showed inconsistent associations with incident hypertension and BP change.

Conclusions: In middle-aged adults without hypertension, cardiovascular disease, or kidney disease, higher urine EGF associated with lower risk of incident hypertension and lower 10-year BP elevations.

Keywords: biomarkers; blood pressure; cardiovascular diseases; hypertension; kidney diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers
  • Blood Pressure / physiology
  • Cardiovascular Diseases*
  • Epidermal Growth Factor / therapeutic use
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Hypertension* / complications
  • Hypertension* / diagnosis
  • Hypertension* / epidemiology
  • Hypotension*
  • Kidney Diseases*
  • Kidney Tubules
  • Male
  • Middle Aged
  • Risk Factors
  • Young Adult

Substances

  • Epidermal Growth Factor
  • Biomarkers