Time-updated systolic blood pressure and the progression of chronic kidney disease: a cohort study

Abstract

Background: Previous reports of the longitudinal association between achieved blood pressure (BP) and end-stage renal disease (ESRD) among patients with chronic kidney disease (CKD) have not incorporated time-updated BP with appropriate covariate adjustment.

Objective: To assess the association between baseline and time-updated systolic blood pressure (SBP) with CKD progression.

Design: Observational, prospective cohort study. (ClinicalTrials.gov: NCT00304148).

Setting: 7 U.S. clinical centers.

Patients: Patients in the Chronic Renal Insufficiency Cohort Study (n = 3708) followed for a median of 5.7 years (25th to 75th percentile, 4.6 to 6.7 years).

Measurements: The mean of 3 seated SBP measurements made up the visit-specific SBP. Time-updated SBP was the mean of that and all previous visits. Outcomes were ESRD and the composite end point of ESRD or halving of the estimated glomerular filtration rate. Analyses investigating baseline and time-updated SBP used Cox proportional hazards models and marginal structural models, respectively.

Results: Systolic blood pressure was 130 mm Hg or greater at all visits in 19.2% of patients. The hazard ratio for ESRD among patients with SBP of 130 to 139 mm Hg, compared with SBP less than 120 mm Hg, was 1.46 (95% CI, 1.13 to 1.88) using only baseline data and 2.37 (CI, 1.48 to 3.80) using time-updated data. Among patients with SBP of 140 mm Hg or greater, corresponding hazard ratios were 1.46 (CI, 1.18 to 1.88) and 3.37 (CI, 2.26 to 5.03) for models using only baseline data and those using time-updated data, respectively.

Limitation: Blood pressure was measured once annually, and the cohort was not a random sample.

Conclusion: Time-updated SBP greater than 130 mm Hg was more strongly associated with CKD progression than analyses based on baseline SBP.

Primary funding source: National Institute of Diabetes and Digestive and Kidney Diseases.

Figure 1

Crude event rates (95% confidence intervals) of ESRD and the renal composite endpoint of ESRD or halving of eGFR from baseline, overall and by level of SBP at baseline in the Chronic Renal Insufficiency Cohort (CRIC) Study. Abbreviations: eGFR – estimated glomerular filtration rate; ESRD – end-stage renal disease; p-y – person-years; SBP – systolic blood pressure.

Figure 2

Estimated cumulative incidence of ESRD across categories of time-updated SBP among participants of the Chronic Renal Insufficiency Cohort (CRIC) Study. Abbreviations: ESRD – end-stage renal disease; SBP – systolic blood pressure.

Figure 3

Forest plot of crude event rates (95% confidence intervals) and multivariable-adjusted hazard ratios per 10 mmHg increase in mean SBP over time on development of ESRD or halving of eGFR overall and by subgroups using marginal structural models. Stratified by clinical center, and adjusted for age, gender, race/ethnicity, education level, history of cardiovascular disease, number of anti-hypertensive medication drug classes taken, use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, hypertension awareness, BMI, diabetes, level of eGFR, urine protein-to-creatinine ratio and study time; Abbreviations: ACE – angiotensin converting enzyme inhibitor; ARB – angiotensin receptor blocker; Ca – calcium; CI – confidence interval; eGFR – estimated glomerular filtration rate; ESRD – end-stage renal disease; NH – non-Hispanic; PCR – protein-to-creatinine ratio; SBP – systolic blood pressure. Age units: years; eGFR units: mL/min/1.73m²; PCR units: mg/mmol.