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

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 meds) 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.

Associations of Proteomics With Hypertension and Systolic Blood Pressure: KORA S4/F4/FF4 and KORA Age1/Age2 Cohort Studies

“…Two cohort studies have reported that urinary KIM1 was not associated with incident hypertension. 33 , 34 In contrast, our present study observed strong positive associations of plasma KIM1 with SBP and hypertension, which is consistent with several cross-sectional studies that have demonstrated positive associations of plasma/serum KIM1 with BP and hypertension. 35 – 37 The difference in biosamples used to measure KIM1 may partially explain these distinct findings.…”

Urine Epidermal Growth Factor and Kidney Function Decline in Middle-Aged Adults

“…In this same group of participants from the CARDIA cohort, we previously found that lower urine EGF levels were uniquely and independently associated with a higher risk of incident hypertension. 35 In combination with our current findings, this work in CARDIA might suggest that early reductions in kidney tubule function may have a causal role in the development of both hypertension and CKD in parallel.…”