Effects of Intensive Systolic Blood Pressure Control on Kidney and Cardiovascular Outcomes in Persons Without Kidney Disease: A Secondary Analysis of a Randomized Trial

Abstract

Background: The public health significance of the reported higher incidence of chronic kidney disease (CKD) with intensive systolic blood pressure (SBP) lowering is unclear.

Objective: To examine the effects of intensive SBP lowering on kidney and cardiovascular outcomes and contrast its apparent beneficial and adverse effects.

Design: Subgroup analyses of SPRINT (Systolic Blood Pressure Intervention Trial). (ClinicalTrials.gov: NCT01206062).

Setting: Adults with high blood pressure and elevated cardiovascular risk.

Participants: 6662 participants with a baseline estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2.

Intervention: Random assignment to an intensive or standard SBP goal (120 or 140 mm Hg, respectively).

Measurements: Differences in mean eGFR during follow-up (estimated with a linear mixed-effects model), prespecified incident CKD (defined as a >30% decrease in eGFR to a value <60 mL/min/1.73 m2), and a composite of all-cause death or cardiovascular event, with surveillance every 3 months.

Results: The difference in adjusted mean eGFR between the intensive and standard groups was -3.32 mL/min/1.73 m2 (95% CI, -3.90 to -2.74 mL/min/1.73 m2) at 6 months, was -4.50 mL/min/1.73 m2 (CI, -5.16 to -3.85 mL/min/1.73 m2) at 18 months, and remained relatively stable thereafter. An incident CKD event occurred in 3.7% of participants in the intensive group and 1.0% in the standard group at 3-year follow-up, with a hazard ratio of 3.54 (CI, 2.50 to 5.02). The corresponding percentages for the composite of death or cardiovascular event were 4.9% and 7.1% at 3-year follow-up, with a hazard ratio of 0.71 (CI, 0.59 to 0.86).

Limitation: Long-term data were lacking.

Conclusion: Intensive SBP lowering increased risk for incident CKD events, but this was outweighed by cardiovascular and all-cause mortality benefits.

Primary funding source: National Institutes of Health.

Appendix Figure 1.

CONSORT flow diagram of study participants. BP = blood pressure; CKD = chronic kidney disease; CONSORT = Consolidated Standards of Reporting Trials; CVD = cardiovascular disease; SBP = systolic blood pressure.

Appendix Figure 2.

Systolic blood pressure separation in the non-CKD population, by treatment group. The mean number of medications was the average number of antihypertensive medication classes prescribed per participant. Closed circles depict raw means. Error bars indicate 95% CIs. CKD = chronic kidney disease.

Appendix Figure 3.

Difference in eGFR during follow-up in the non-CKD population. Adjusted means (intensive minus standard group) with 95% CIs (error bars) are shown. Open circles depict fasting visits; closed circles depict nonfasting visits. CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate.

Appendix Figure 4.

Forest plot of HRs for incident CKD (>30% decrease from baseline) in the entire non-CKD population and in subgroups defined by age, sex, race, and albuminuria (urinary albumin–creatinine ratio <30 vs. ≥30 mg/g). CKD = chronic kidney disease; HR = hazard ratio.

Appendix Figure 5.

Cumulative incidence of albuminuria in non-CKD subgroup. CKD = chronic kidney disease.

Figure 1.

Predicted mean eGFRs and 95% CIs (error bars) from a linear model accounting for baseline eGFR in the non-CKD population. Results from nonfasting (left) and fasting (right) visits, including the raw (unadjusted) baseline mean. CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate.

Figure 2.

Cumulative incidence plots for incident CKD (A), primary CVD outcome (B), all-cause death (C), and the composite of primary CVD outcome or all-cause death (D) in the non-CKD population, by treatment group. CKD = chronic kidney disease; CVD = cardiovascular disease.

Figure 3.

Final status of participants with incident CKD. Final disposition (categorized as non-CKD, CKD with varying decreases in eGFR, ESRD, or death) of persons who met the criteria for incident CKD during follow-up in the intensive (top) and standard (bottom) groups. The mean (SD) end-of-study eGFR is provided for each category. The 180 incident CKD events occurred a median of 21.0 mo (range, 1.2 to 47.9 mo) after randomization. The final eGFR assessments for patients with incident CKD occurred 42.4 mo (range, 11.4 to 58.9 mo) after randomization. CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease.