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

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.

Fig 1. Flowchart of the study participants.

Abbreviations: eGFR: estimated glomerular filtration rate; BP: blood pressure; HT: hypertension; aTRH: apparent treatment-resistant hypertension; cHT: controlled HT; ucHT: uncontrolled hypertension with ≤ 2 antihypertensive drugs; Persistent cHT: controlled hypertension during the 4-year follow-up; Persistent ucHT: uncontrolled hypertension with ≤ 2 antihypertensive drugs during the 4-year follow-up.

Fig 2. Prevalence of hypertension control status according to GFR estimated from the MDRD, the CKD-EPI and the BIS1 equations at baseline.

Abbreviations: cHT: controlled hypertension; aTRH: apparent treatment resistant hypertension; ucHT: uncontrolled nonresistant hypertension with ≤ 2 antihypertensive drugs; eGFR: estimated glomerular filtration rate; MDRD: Modification of Diet in Renal Disease study; CKDP-EPI: Chronic kidney disease epidemiology collaboration; BIS1: the Berlin Initiative Study equation 1. eGFR categories in mL/min per 1.73m²: ≥60, 45–59 and <45. p-value for global comparison of frequencies of aTRH, cHT and ucHT according to eGFR levels was < 0.001 for each equation.