Blood pressure targets for the prevention of chronic kidney disease: the discrepancies between observational studies and randomized controlled trials
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Hypertension is a major cause of chronic kidney disease (CKD), with a strong bidirectional relationship between the two conditions. Although hypertension is highly prevalent among CKD patients, most studies in the general population focus on its association with the risk of cardiovascular disease and mortality rather than CKD incidence as an outcome. Moreover, while many hypertension guidelines suggest target blood pressure (BP) levels for CKD patients, there is no specific BP target recommended for the prevention of CKD incidents in the general population. Lim et al. [1] reported the association between systolic BP (SBP) and the risk of incident CKD in a large cohort. They studied 195,970 participants from Korea’s nationally representative sample cohort, all of whom had no clinical CKD at baseline. The absence of CKD at baseline was defined by an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 and no dipstick proteinuria. Time-dependent SBP was treated as both a continuous and categorical variable (<110, 110–119, 120–129, 130–139, and ≥140 mmHg). After 5 years of follow-up, CKD was defined as a composite event of a decrease in eGFR <60 mL/min/1.73 m2 or a newly developed proteinuria (higher than 1+ level on a urine dipstick test). The authors used three different statistical models to estimate the association between SBP and the risk of incident CKD.
During the 5-year follow-up period, the authors noted that a total of 3,355 participants (1.7%) developed an incident of CKD. The study found that increasing SBP was significantly associated with a higher risk of CKD, particularly when analyzed as a continuous variable. In contrast, when SBP was treated as a categorical variable, SBP of 130–139 and ≥140 mmHg groups were associated with a higher risk of incident CKD, while the SBP <110 mmHg group was associated with a lower risk compared to the SBP of 120–129 mmHg group, regardless of the statistical model used. However, a lower risk of incident CKD was observed for the SBP of 110–119 mmHg group only with the marginal structural model (MSM). These analyses were adjusted for demographics, social covariables, and medical comorbidities. Interestingly, the results remained consistent across different follow-up periods. The strengths of the study include the large sample size and availability of detailed sociodemographic information, comorbidities, and laboratory data. Various statistical models were used to obtain consistent results and enhance the reliability of the study. In particular, the application of the MSM, which accounts for time-dependent confounding and causal inference, addresses the shortcomings of previous studies that relied on the simple Cox regression model. The MSM analysis also revealed a more linear relationship between SBP and incident CKD.
Previous observational studies have also demonstrated that lower BP is associated with a decreased incident CKD and end-stage kidney disease (ESKD) in the general population [2–4]. For instance, SBP >120 mmHg was significantly associated with a higher risk of CKD or ESKD. However, randomized controlled trials (RCT) and meta-analyses have shown different results from observational studies. Meta-analysis results showed that intensive BP lowering to <130/80 mmHg did not provide additional beneficial effects on renal outcomes in both diabetic and non-diabetic patients [5,6], and no randomized trial has demonstrated a renal benefit from intensive BP control beyond standard treatment [7]. The discrepancies between observational studies and RCT are not merely due to differences in research methods but may also be partly explained by the differences in the baseline characteristics of the study populations (Fig. 1). Observational studies often include healthier participants with fewer comorbidities, while the RCT participants tend to be higher-risk patients, especially those with high cardiovascular risk and comorbidities. In high-risk patients, intensive BP control could lead to complications such as acute kidney injury due to hemodynamic effects [8,9]. Based on these results, we can infer that the optimal BP target will differ for healthy individuals with few comorbidities and those at high risk with many comorbidities.
Discrepancies in optimal BP between observational studies and randomized controlled trials.
Current guidelines set target BP based on the results of randomized controlled trials. However, observational cohort study results show that the optimal BP may be lower than the target BP range suggested by the current guidelines.
BP, blood pressure; CKD, chronic kidney disease.
As the authors note, this study inherits the limitations of observational cohort studies using claims data. The impact of diastolic BP on incident CKD has not been extensively studied to date [10]. In a similar context, research on the lower limit of BP with renal benefit is also an area that should be addressed in the future. Furthermore, the study population consisted of both hypertensive and no-hypertensive individuals, as well as those on antihypertensive medication and those not. Although adjustments were made for antihypertensive medication history, this remains an important potential confounder. To overcome these limitations and provide clear BP targets for preventing incident CKD in the general population, a well-designed, RCT with carefully selected subjects and defined BP targets is essential. Additionally, a personalized treatment strategy is necessary, with different BP targets for each individual.
Notes
Conflicts of interest
Eun Hui Bae is an Associate Editor of Kidney Research and Clinical Practice and was not involved in the review process of this article. All authors have no other conflicts of interest to declare.
Data sharing statement
The data presented in this study are available from the corresponding author upon reasonable request.