Chronic kidney disease (CKD) is a global health concern worldwide. It is currently estimated [1] that nearly 700 million patients worldwide suffer from CKD, which poses a heavy burden on the medical and economic system. CKD patients have a protracted disease course and poor prognosis and are frequently susceptible to numerous organ abnormalities, increasing the risk of death [2]. As one of the top 10 non-communicable causes of death worldwide [3], clinicians are looking for ways to prevent CKD from occurring and developing.

Some novel therapies for CKD treatment have become widely available for clinicians, and new hypoglycemic medications, such as sodium glucose cotransporter-2 inhibitors, have been shown to improve cardiac and renal outcomes in diabetic and non-diabetic CKD patients [4, 5]. In addition to pharmacological therapies, lifestyle interventions such as healthy diets, sodium restriction, and physical activity (PA) are also critical to improving patients’ conditions [6, 7]. For the general population, PA has been proven to reduce the risk of mortality and improve the status of insulin resistance and mental health [8, 9, 10]. Furthermore, some studies demonstrated that PA might reduce the cardiovascular risk of death and improve cardiopulmonary function in CKD patients [11, 12, 13]. Other related research also implied that a certain degree of PA is associated with a reduced risk of mortality and cardiovascular death in CKD patients regardless of diabetes [14]. However, there is currently a lack of studies focusing on the association of leisure-time physical activity (LTPA) intensity and daily duration with the risk of mortality in CKD patients with or without cardiovascular diseases (CVD). There is great heterogeneity among CKD patients [15]. For CKD patients complicated with CVD, their cardiorespiratory fitness is often worse, and the risk of death from CVD and other cerebrovascular diseases is significantly increased [16]. In addition, such patients may be more intolerant of a high-level LTPA that is superior to their own exercise capacity. Therefore, this study aims to conduct a secondary analysis of an observational cohort study based on information collected from the National Health and Nutrition Examination Survey (NHANES) database to investigate the association of LTPA intensity and duration with the risk of all-cause death.

PA has been demonstrated to improve cardiorespiratory fitness and reduce the risk of cardiovascular and renal outcomes in the general population [9, 19]. According to the guidelines from the Kidney Disease: Improving Global Outcomes (KDIGO), physical activities should be recommended as a routine treatment for patients with CKD [20]. Nevertheless, the association of LTPA intensity and daily exercise time with mortality risk in CKD patients complicated with CVD remains unclear.

Our study is the first to focus on investigating the survival benefits of LTPA in patients with CVD. We found that moderate LTPA is associated with a reduced risk of mortality for general CKD patients. However, vigorous LTPA did not have any significant benefits in their conditions. These results raise questions about whether patients with CKD can benefit from vigorous exercise. We assume that there might be different reasons behind our primary results. First, the inclusion of some covariates (e.g., eGFR and age, which may reflect the progression of diseases and is associated with a certain level of mortality) may modify the benefit of LTPA on CKD patients. Secondly, the number of patients who exercised vigorously was considerably smaller than the samples in other studies, which may cause a particular risk of bias. It is important to mention that several studies also have similar results as us, Beddhu et al. [12] conducted a study based on the NHANES database and found that light-intensity LTPA may help reduce the risk of mortality in CKD patients. while moderate or vigorous intensity was not associated with a lower risk of death. Differently, Kim J. et al. [21] demonstrated that a low and moderate amount of PA was associated with a lower risk of all-cause death; however, vigorous exercise still did not have considerable benefits. It is unclear whether vigorous PA intensity can help improve the prognosis of CKD patients. Given most of the research was observational and relied on self-reported data, further high-quality studies are needed to validate the association between vigorous PA intensity and potential benefits for patients diagnosed with CKD.

Cardiovascular diseases are the leading cause of death in patients with CKD [16, 22], which sheds light on the importance of a reasonable PA prescription for patients with CVD complications. Our subgroup analysis identified different survival benefits for patients with or without CVD. LTPA did not see a clear survival benefit for patients complicated with CVD, suggesting that physical exercise may have individual differences in the survival benefits of the CKD population. It’s worth mentioning that research on the impact of LTPA on these patients has been limited. Some studies have demonstrated that regular exercise can reduce the risk of cardiovascular and all-cause death in individuals with heart failure [23, 24]. Furthermore, several studies also revealed that higher levels of PA were associated with a lower risk of mortality in patients with coronary artery calcification [25]. Nonetheless, these studies did not analyze the subgroups of patients with CKD. According to our research, LTPA may not bring survival benefits for CKD patients complicated with CVD. However, our results also pointed out that moderate LTPA reduced mortality risk in patients without cardiovascular disease, showing that physical exercise may have varying survival benefits for CKD patients with various baseline characteristics. In the future, more high-quality studies are needed to find out how physical activity affects patients with CKD with different individual features.

The ideal duration of daily physical activity for those with CKD is still unclear. Our study found that LTPA for more than 30 minutes per day is associated with a reduced risk of mortality for general CKD patients. However, when the time went beyond 110 min/d, the relative risk value reached a plateau effect. Previously, an observational study conducted by Zhang NH pointed out that the risk of mortality was relatively increased in CKD patients who reported more than 900 min/week of LTPA. However, it was not statistically significant [11]. In light of these findings, we propose that the dose of LTPA should be reasonably controlled for patients with CKD rather than being excessive or too low.

It is noteworthy that different exercise periods did not diminish the mortality risk in CKD patients with CVD. This demonstrates that LTPA does not improve survival outcomes in CKD patients complicated with CVD, which is consistent with the findings related to LTPA intensity in our study. We assume that this may be due to the high heterogeneity among CKD patients [15] and the critical condition of patients complicated with CVD, since most patients with CVD are exposed to a higher risk of disease progression and all-cause mortality [16]. In contrast, patients without CVD had better tolerance to physical exercise. Our results showed that, in these cases, LTPA for more than 30 minutes per day was associated with reduced mortality risk. Our outcomes challenge the results presented by Kim MH in a previous study that indicated that longer weekly periods of PA were associated with lower risks of all-cause death in the general population, regardless of whether or not they had CVD [26]. The varying conclusions may be because the enrolled patients in our study were different since the proportion of CKD in that study only accounted for 5%, and those who had their conditions complicated with CVD had a lower mean eGFR level (53 versus 67 mL/min/1.73 m${}^2$). In addition, the survey method we applied focuses on the patient’s weekly fixed exercise intensity and frequency rather than the exercise level recalled in the past 7 days, so the results are more reliable. According to our observations, patients with CKD who engage in at least 30 minutes of moderate LTPA each day are associated with lower mortality risk. This dose is also in line with the standard recommendation of the KDIGO guideline.

It is equally important to acknowledge the limitations of our study. First, the population enrolled in our study involved mainly stage 1–4 CKD individuals, while stage 5 CKD patients and those who undergo dialysis (who are high-risk groups for CVD complications) still need to be included in more detailed research. Second, since CKD patients are exposed to weakened cardiopulmonary systems and prone to a high level of frailty index, they may have a lower PA capacity compared with healthy individuals. The use of MET as a metric for assessing exercise intensity may result in some bias. This is also the limitation of most current observational studies. Future studies should focus on using an individual’s PA capacity as a way to measure the intensity of PA. Third, most of the baseline characteristics of the various LTPA intensity groups were different. Although we were dedicated to controlling the confounding factors in the regression model, there may still be other factors interfering with the reliability of the results.

We have concluded that moderate LTPA for more than 30 minutes is directly associated with a reduced risk of mortality in general CKD patients. This advantage was also evident in individuals without CVD. Nonetheless, LTPA was not associated with an improved survival outcome in CKD patients complicated with CVD. Our findings indicate that the survival benefit of LTPA in patients with CKD appears to vary depending on the individual with or without CVD, emphasizing the significance of tailoring PA prescriptions to the individual characteristics of the CKD population.

The datasets used and analyzed in this study are available from the first author and corresponding author on reasonable request.

NL, LZ contributed to the concept and design of this study. NL, WGZ, YWZ were responsible for statistical analysis and writing of the report, RYH, JCZ, and MYK assisted in statistical analysis, ECZ, WS reviewed the article and provided critical feedback to improve and structure the report. All authors read and approved the final manuscript.

Since the current study was a secondary analysis of data from the NHANES database, which are publicly available, no institutional review board approval was necessary or obtained. In the NHANES database, written informed consent was obtained from all participants. And for this analysis, no informed consent was required from patients since all the data were de-identified when we conducted the investigation.

Not applicable.

This study was supported by the Special Project of National Clinical Research Base of Traditional Chinese Medicine (No. JDZX2015094).

The authors declare no conflict of interest.