Chronic kidney disease (CKD) describes a cluster of conditions resulting from various factors that cause the kidneys to have abnormal structure or function for a duration exceeding 3 months. According to relevant research reports (1, 2), the global prevalence of CKD is about 9.1%. Chronic kidney disease has induced a heavy burden on the global public health system. Currently, the prevalence of CKD in the US health insurance system has reached 14.5% (3, 4). The development of CKD is intimately linked to genetic factors, environmental factors, and nutritional factors (5–7). Current research indicates that trace elements play a pivotal role in preventing and treating various diseases (8). Studies have also found that CKD is closely related to nutrition and diet (9, 10). Therefore, identifying these controllable factors, such as diet and the intake of natural compounds, might help to prevent and treat CKD.

Selenium is crucial for human and animal life activities, affecting many physiological functions of the human body, and playing a key role in anti-inflammatory and antioxidant processes (11). Humans cannot synthesize selenium, which must be obtained from external intake. Selenium is mainly enriched in the human kidney, where it can be used to synthesize various selenoproteins. The essential role of selenium in the human body is primarily fulfilled by 25 selenoproteins, with selenocysteine serving as the active component (12, 13). These selenoproteins function as inhibitors of non-specific immune responses and inflammatory reactions, as well as factors affecting reproduction and oxidative stress. During the recovery period after injury, some selenoproteins (such as glutathione peroxidase 4 (GPX4), GPX1, selenoprotein P, and selenoprotein S) can interact to produce numerous anti-inflammatory and antioxidant activities, and can reduce the production of certain superoxide radicals that cause inflammatory reactions (14, 15). Previous studies have shown that the serum selenium content of patients with CKD is lower than that of healthy people, and selenium deficiency is closely related to the occurrence of CKD. and the decrease is more pronounced in patients receiving hemodialysis (15, 16). Studies have shown that selenium administered orally or by intravenous injection can improve the immune function of patients with CKD and reduce oxidative stress-induced kidney damage (17–19). Therefore, appropriate selenium supplementation might help to reduce the risk of CKD.

Currently, most selenium-containing drugs have different limitations and side effects, such as causing gastroenteritis, acropachy, and cognitive function decline (20). Therefore, increased research attention has been paid to dietary methods of selenium supplementation. Many natural compounds, such as phosphorus, vitamin D, magnesium and other nutrients have also been shown to have a certain preventive and therapeutic effect on CKD (21–23). However, according to our investigation, there is no study directly discussing the correlation between dietary selenium and CKD at present.

Therefore, in this study, we used 4 years of NHANES data (2015–2018) to investigate the relationship between dietary selenium intake and CKD. In addition, we explored whether this relationship varied among individuals according to age, sex, weight, and disease status. We hypothesized that a higher selenium intake is inversely associated with the incidence of CKD.

To the best of our knowledge, there have been few studies concerning the connection between dietary selenium and CKD. In this cross-sectional study, after adjusting for confounding factors such as sex, age, race, marital status, education level, smoking status, poverty rate, carbohydrate intake, BMI, diabetes, hypertension, C-reactive protein, triglycerides, total cholesterol, serum uric acid, and dietary selenium supplement intake, we confirmed the reliability of the significant negative correlation between dietary selenium intake and the incidence of CKD. In the population studied, we found that after adjusting for other confounding factors, the risk of CKD decreased by 7.7% for every additional 0.1 mg of dietary selenium intake.

The United States Food and Nutrition Board (FNB) has found that the demand for selenium increases with age, and it is recommended that people under the age of 30 consume 50–100 micrograms of selenium per day, while people over the age of 30 should consume 100–200 micrograms of selenium per day to help prevent genetic diseases and related chronic diseases (29–31). We took into account the different recommended doses for people over and under the age of 30, and primarily focused on examining the association between dietary selenium intake and CKD among individuals aged 30 and above in the United States.

Compared with other trace elements, selenium plays an important role in the human body, especially in anti-inflammatory, antioxidant, and immune regulation processes (32, 33). Currently, the association between selenium intake and CKD is controversial. In this study, we confirmed the negative correlation between selenium and the occurrence of CKD. Similarly, Xie et al. (34) found that among 5,381 middle-aged and elderly people in the China Health and Nutrition Survey (CHNS) database, the CKD prevalence was 23.33 and 9.25% in people with daily selenium intake levels of 21.5 ± 4.82 μg/day and 67.0 ± 13.97 μg/day, respectively. The occurrence of CKD was 2.5 times greater in the group with low selenium intake compared with that in the group with high selenium intake. A higher selenium intake might play a positive role in renal function. This finding is consistent with the results of the present study. Zhu et al. (35) studied 3,063 CKD patients in the NHANES database (during 1999–2000, 2003–2004, and 2011–2018) found that the serum selenium levels <156.8 μg/L and 201.5–734.8 μg/L had a 10-year mortality risk ratio (HRs; 95% CI) of 0.866 (0.724–1.035) and 0.684 (0.549–0.852) (P trend<0.001), respectively. However, the serum selenium content in CKD patients receiving dialysis treatment may be affected by blood dialysis, there may be survivor bias in analyzing the relationship between serum selenium levels and mortality risk in CKD patients. Compared with serum selenium, the dietary structure of the population is often more stable, so there are fewer factors that can interfere with the study of dietary selenium.

Fu et al. (36) conducted a Mendelian randomization analysis of 9,639 large-scale genome-wide association studies in Europe and found that the serum selenium level exhibits a negative correlation with the estimated glomerular filtration rate (eGFR) among European individuals (HR = −0.0042, 95% CI: −0.0053–0.0031, p = 2.186 × 10⁻¹³), which seems to be contrary to our results. We speculate that there are several possible explanations for this difference. First, dietary selenium intake levels and baseline serum selenium levels have distinct differences. Second, studies have shown that serum selenium levels are easily affected by oxidative stress status in the human body (37), while daily dietary conditions are less affected by oxidative stress status. Finally, the study population is different, and the results may be affected by geographical, ethnic, genetic, and other relevant factors.

Some animal clinical trials have also found that dietary intake or oral selenium supplements can alleviate kidney injury and renal fibrosis to a certain extent in rats, thereby improving renal function (38, 39). Based on this, we analyzed the relationship between dietary selenium intake and CKD patients. This may provide a theoretical basis for future researchers to conduct clinical controlled trials of selenium and CKD.

The biological mechanism between dietary selenium intake and CKD is currently unclear but it might be linked to the following mechanisms. Selenium can reduce oxidative stress injury by regulating immune responses, inhibiting inflammatory factor release, and downregulating TGF-β1 expression of cytokines to reduce kidney damage and improve renal function in patients (14, 33, 40). Selenium is an important component of several antioxidant enzyme substances and can also enhance the antioxidant effects of non-enzyme substances such as vitamin E and coenzyme Q-10. Therefore, selenium can reduce oxidative stress reactions in the human body to a certain extent and protect the kidneys (12). Finally, our study results supported the positive role of selenium in preventing CKD.

Since our current research aims to verify or explore a specific hypothesis or theory, The formula for converting serum creatinine in the CKD-Dietary Modification of Renal Disease (CKD-MDRD) study into estimated glomerular filtration rate (eGFR) has undergone long-term validation, comparison with the latest formula this formula has higher authority. Therefore, we chose the CKD-MDRD equation, published in the Journal of the American Society of Nephrology in 2006, to calculate the glomerular filtration rate when assessing the renal function of the included population.

There are some advantages in our current study. As far as we know, this is the initial study to examine the relationship between dietary selenium intake and CKD among American adults. Additionally, we have also evaluated the correlation between selenium intake and CKD, and provided some practical suggestions. However, there are also some disadvantages in this study. Firstly, our findings are specific to the American adult population and may not be generalized to other global populations. Secondly, in this study, we diagnosed CKD based on serum creatinine levels and proteinuria, the NHANES database lacks kidney imaging data, and we may miss some patients with CKD. Therefore, to some extent, we may have missed some CKD patients. Future studies can appropriately incorporate renal imaging results for diagnosis if possible. Thirdly, we only studied the sample data of American adults from 2015 to 2018. Future studies can conduct more extensive and larger sample size studies. At last, our current study is a cross-sectional investigation, and as such, it cannot establish a valid cause-and-effect relationship. Therefore, in future studies, we need to conduct prospective longitudinal studies to further confirm the relationship between selenium and CKD.

In conclusion, through our study, we found that the daily dietary selenium intake of American adults is significantly negatively correlated with the incidence of CKD.

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: http://www.cdc.gov/nchs/nhanes.htm.

The research conducted in this study involved the analysis of a nationally representative public dataset that has been openly published online and is accessible for download and analysis by anyone. The studies were conducted in accordance with the local legislation and institutional requirements. The human samples used in this study were acquired from the blood samples were provided by the NHANES database. Written informed consent for participation was not required from the participants or the participants' legal guardians/next of kin in accordance with the national legislation and institutional requirements.

YP: Writing – original draft, Formal analysis. XL: Writing – original draft. XS: Validation, Writing – review & editing. YC: Writing – review & editing, Validation. XT: Writing – review & editing, Formal analysis. GL: Writing – review & editing, Conceptualization. YZ: Writing – review & editing, Conceptualization.