Inflammation and Apparent Treatment-Resistant Hypertension in Patients With Chronic Kidney Disease

Hypertension. 2019 Apr;73(4):785-793. doi: 10.1161/HYPERTENSIONAHA.118.12358.


Apparent treatment-resistant hypertension (ATRH) is highly prevalent and associated with cardiovascular disease risk in patients with chronic kidney disease. We analyzed the association of inflammatory biomarkers with ATRH and its complications in patients with chronic kidney disease. ATRH was defined as blood pressure ≥140/90 mm Hg while taking ≥3 antihypertensive medications or blood pressure <140/90 mm Hg while taking ≥4 medications. Analyses included 1359 CRIC study (Chronic Renal Insufficiency Cohort) participants with ATRH and 2008 hypertensive participants without. Logistic regression was used to examine cross-sectional associations of inflammatory biomarkers and ATRH adjusting for demographic, lifestyle, and clinical risk factors and treatments. Cox proportional hazards models were used to assess the impact of inflammatory biomarkers on associations of ATRH with composite cardiovascular disease and mortality beyond conventional risk factors. Multivariable-adjusted odds ratio (95% CI) of ATRH for the highest tertile versus the lowest tertile of inflammatory biomarker levels was 1.29 (95% CI, 1.05-1.59) for IL (interleukin)-6, 1.49 (95% CI, 1.20-1.85) for TNF-α (tumor necrosis factor-α), and 0.77 (95% CI, 0.63-0.95) for TGF-β (transforming growth factor-β). High-sensitivity CRP (C-reactive protein), fibrinogen, IL-1β, and IL-1 receptor antagonist were not significantly associated with ATRH. Adding inflammatory biomarkers to Cox models did not attenuate the significant association of ATRH with cardiovascular disease and mortality. Our findings show higher levels of IL-6 and TNF-α and lower levels of TGF-β were independently associated with odds of ATRH. Targeting specific inflammatory pathways may improve blood pressure control in patients with chronic kidney disease.

Keywords: cardiovascular diseases; hypertension; inflammation; patients; renal insufficiency, chronic.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Biomarkers / blood
  • Blood Pressure / physiology*
  • Comorbidity
  • Cross-Sectional Studies
  • Cytokines / blood*
  • Drug Resistance
  • Female
  • Glomerular Filtration Rate / physiology*
  • Humans
  • Hypertension / blood
  • Hypertension / drug therapy
  • Hypertension / epidemiology*
  • Inflammation / blood*
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / epidemiology*
  • Renal Insufficiency, Chronic / physiopathology
  • Risk Factors
  • United States / epidemiology
  • Young Adult


  • Antihypertensive Agents
  • Biomarkers
  • Cytokines