Kidney Function Decline and Apparent Treatment-Resistant Hypertension in the Elderly

PLoS One. 2016 Jan 25;11(1):e0146056. doi: 10.1371/journal.pone.0146056. eCollection 2016.

Abstract

Background: Cross-sectional studies show a strong association between chronic kidney disease and apparent treatment-resistant hypertension, but the longitudinal association of the rate of kidney function decline with the risk of resistant hypertension is unknown.

Methods: The population-based Three-City included 8,695 participants older than 65 years, 4265 of them treated for hypertension. We estimated the odds ratios (OR) of new-onset apparent treatment-resistant hypertension, defined as blood pressure ≥ 140/90 mmHg despite use of 3 antihypertensive drug classes or ≥ 4 classes regardless of blood pressure, associated with the mean estimated glomerular filtration rate (eGFR) level and its rate of decline over 4 years, compared with both controlled hypertension and uncontrolled nonresistant hypertension with ≤ 2 drugs. GFR was estimated with three different equations.

Results: Baseline prevalence of apparent treatment-resistant hypertension and of controlled and uncontrolled nonresistant hypertension, were 6.5%, 62.3% and 31.2%, respectively. During follow-up, 162 participants developed apparent treatment-resistant hypertension. Mean eGFR decline with the MDRD equation was 1.5±2.9 mL/min/1.73 m² per year: 27.7% of the participants had an eGFR ≥3 and 10.1% ≥ 5 mL/min/1.73 m² per year. After adjusting for age, sex, obesity, diabetes, and cardiovascular history, the ORs for new-onset apparent treatment-resistant hypertension associated with a mean eGFR level, per 15 mL/min/1.73 m² drop, were 1.23 [95% confidence interval 0.91-1.64] compared to controlled hypertension and 1.10 [0.83-1.45] compared to uncontrolled nonresistant hypertension; ORs associated with a decline rate ≥ 3 mL/min/1.73 m² per year were 1.89 [1.09-3.29] and 1.99 [1.19-3.35], respectively. Similar results were obtained when we estimated GFR with the CKDEPI and the BIS1 equations. ORs tended to be higher for an eGFR decline rate ≥ 5 mL/min/1.73 m² per year.

Conclusion: The speed of kidney function decline is associated more strongly than kidney function itself with the risk of apparent treatment-resistant hypertension in the elderly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Albuminuria / epidemiology
  • Albuminuria / etiology
  • Antihypertensive Agents / therapeutic use
  • Causality
  • Comorbidity
  • Creatinine / blood
  • Diabetes Mellitus / epidemiology
  • Disease Progression
  • Drug Resistance
  • Drug Therapy, Combination
  • Follow-Up Studies
  • France / epidemiology
  • Glomerular Filtration Rate
  • Humans
  • Hypercholesterolemia / epidemiology
  • Hypertension / drug therapy*
  • Hypertension / epidemiology
  • Hypertension / etiology
  • Hypertension, Renal / diagnosis
  • Hypertension, Renal / epidemiology
  • Middle Aged
  • Obesity / epidemiology
  • Odds Ratio
  • Prevalence
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / physiopathology
  • Sensitivity and Specificity
  • Sex Factors

Substances

  • Antihypertensive Agents
  • Creatinine

Grants and funding

The Three-City Study was conducted under a partnership agreement between the Institut National de la Santé et de la Recherche Médicale (INSERM), the Victor Segalen– Bordeaux II University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The Fondation Plan Alzheimer partly funded the follow-up of the study. The 3C Study was also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques”. The study also received a grant from the Agence Nationale de la Recherche (ANR). The CKD ancillary study at the 4-year follow-up was granted by the French-speaking Society of Nephrology. Jean Kaboré was supported by a research grant from the French Ministry of Research. No donors played a role in the design and the conduct of the study.