The results published in the JAMA Network Open indicate that the effects of intensive vs. standard blood pressure (BP) targets seen in clinical trials may not translate in clinical practice when patients with chronic kidney disease (CKD), particularly those with comorbidities, and cardiovascular risk factors.
The management of CKD focuses on reducing morbidity associated with hypertension. According to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines the treatment aims to achieve a blood pressure (BP) target of <120 mm Hg by using the methods to maximize patient tolerance. Recommendations from the SPRINT prespecified subgroup analysis of CKD participants would suggest that treatment to a systolic BP target of <120 mm Hg compared to <140 mm Hg is associated with lower mortality by reducing cardiovascular events and decreased risk of mild cognitive impairment. However, this approach carries a high risk of adverse events like acute kidney injury.
The generalization of SPRINT findings of the U.S. population is limited, due to the small number of NHANES subjects with advanced CKD making its applicability to routine practice questionable. Another key controversy of the KDIGO BP target is the difficulty in extrapolating SPRINT results of adults with CKD in typical clinical settings. While randomized trials have high internal validity they often fail to account for the risks and benefits in broader clinical populations. Trial eligibility criteria and enrollment procedures result in study populations with characteristics distinct from routine patients by leading to biased treatment effect estimates and potentially invalid conclusions about the clinical value of new interventions.
Intensive BP treatment offers limited benefits for adults with CKD, collected with insufficient data on associated adverse events. This uncertainty raises concerns about the net benefit of intensive BP control in this population. While SPRINT subgroup analyses of CKD status suggested potential modifications in cardiovascular outcomes as they did not provide definitive evidence to support the findings.
Cardiovascular benefits from intensive BP treatment may be decreased in patients with advanced CKD as suggested by post hoc analyses of SPRINT, large meta-analyses, and observational studies.
The study includes 3 different data sources. Various target populations of interest are defined in SPRINT and 2 distinct electronic health record databases, of which publicly available data is used. Results of primary outcomes in SPRINT have been reported previously. Adults without diabetes and with hypertension and elevated cardiovascular risk due to the presence of CKD or other cardiovascular risk factors were enrolled in the SPRINT, an open-label, nonblinded randomized clinical trial.
The SPRINT trial included 9,361 participants, and the CKD subgroup included 2,646 participants. Participants in SPRINT were followed from randomization (August 2003) until dropout, death, or trial termination (August 20, 2015) with a median follow-up of 3.3 years. Here, the team included a total of 85,938 VHA (mean [SD] age 75.7 [10.0] years, 81,628 [95.0%] male) and 13,983 KPSC (mean [SD] age 77.4 [9.6] years, 5,371 [38.4%] male) adults from the VHA and CKD and hypertension cohort.Â
In this study, a total of 85,938 patients (mean [SD] age, 75.7 [10.0] years; 81 628 [95.0%] male) from the VHA and 13 983 patients (mean [SD] age, 77.4 [9.6] years; 5371 [38.4%] male) from KPSC were included. Adults with VHA CKD and hypertension cohort were older, predominantly male, and more likely to be White or of another ethnicity. The SPRINT population was less likely to have cardiovascular conditions and more likely to smoke, they were also more likely to be treated with statins. Also, they had a higher Framingham risk score, UACR, fewer BP medications, and lower HDL and LDL. The KPSC CKD and hypertension cohort adults were older, more female, more Hispanic or other race or ethnicity, and different from the SPRINT population. People in the Kleim population were more likely to have cardiovascular disease, smoke, and use statins than a SPRINT population.
The primary outcome was a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, and cardiovascular-related mortality all adjudicated. Secondary outcomes included all-cause mortality, individual major adverse cardiovascular events, adjudicated dementia or mild cognitive impairment, and CKD progression which was defined as a composite of 50% decline in eGFR or development of kidney failure requiring chronic dialysis or kidney transplant.
Reference: Kurella Tamura M, Huang M, An J, et al. SPRINT Treatment Among Adults With Chronic Kidney Disease From 2 Large Health Care Systems. JAMA Network Open. 2025;8(1):e2453458. doi:https://doi.org/10.1001/jamanetworkopen.2024.53458Â
