Association between high fat diet and kidney stones based on the National Health and Nutrition Examination Survey (NHANES) 2007–2020: a cross-sectional study

Introduction

Kidney stones (KS) represent a significant clinical and public health challenge, characterized not only by high initial incidence but also by a pronounced tendency for recurrence—with rates reaching 50% within five years and 75% within 20 years (1,2). Despite effectively removing existing stones, current treatments often fail to address the underlying predispositions, as evidenced by the high recurrence rate. Beyond recurrence, KS are associated with a range of acute and chronic complications, including lower back pain, haematuria, urinary tract infections, and in severe cases, progressive kidney damage or even end-stage renal disease (3-5). Collectively, these clinical manifestations contribute to substantial physical discomfort, reduced quality of life, and considerable financial and social burdens in affected individuals (6). Thus, identifying modifiable risk factors remains a critical priority in KS prevention.

High fat diet (HFD) is becoming increasingly common worldwide. From 1980 to 2013, fat intake as a proportion of total nutritional intake has increased (7). In addition, the percentage of energy from total dietary fat consumed by American adults increased from 32% to 33.2% from 1999 to 2016 (8). An HFD accelerates the process of lipid precipitation in both fat cells and other cells (9), which further leads to diet-induced obesity (DIO). Obesity and metabolic problems are considered contributors to the development of KS (10,11).

Although HFD is a recognized driver of DIO and metabolic diseases, its role as an independent dietary pattern in KS development remains inadequately characterized. A recent study by Tan and Zhang provided important insights by demonstrating that specific dietary fatty acids—saturated, monounsaturated, and polyunsaturated—are individually associated with KS risk (12). However, this nutrient-specific approach does not address the collective impact of a generalized high fat dietary pattern, which is more relevant for practical dietary guidance. Furthermore, while previous studies by D’Amico et al. and Taylor et al. have linked composite dietary patterns to nephrolithiasis risk, they did not isolate the specific contribution of overall dietary fat content (13,14). To address this gap, our study was performed to identify the association between HFD and the formation of KS and to provide a novel way to prevent the formation and progression of KS. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-333/rc).

Methods

Study population

This study was performed to explore the association between HFD and KS based on publicly available data from the National Health and Nutrition Examination Survey (NHANES, 2007–2020) database. The NHANES database collects representative samples of the non-institutionalized civilian population in the United States via a national, multi-stage, stratified cluster design. The NHANES collects information on the health and dietary status of U.S. civilians every two years through questionnaires, physical examinations, and laboratory tests. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Initially, our research included 66,148 participants based on data collected from 2007 to 2020. The exclusion criteria included: age under 20 years, missing HFD or KS information, and missing covariate data. Thus, the final dataset consisted of 31,059 participants, as shown in Figure 1.

Figure 1 Flowchart of the sample selection from NHANES 2007–2020. NHANES, National Health and Nutrition Examination Survey.

Definition of HFD and KS

On the basis of the World Health Organization (WHO) recommended intake for healthy diets, a daily fat energy ratio >30% was regarded as an HFD in our study (13). The dietary data for each participant were collected through 24-hour dietary recall interviews. In this phase, every NHANES participant completed two interviews: first, a dietary memory interview was conducted at the Mobile Examination Center, and then three to ten days later, the other interviews were conducted over the phone. Considering the large amount of missing dietary data for the second interview, these data were not included in our data analysis. The daily fat intake (g) and total daily dietary energy intake (kcal) of the participants were extracted. Using the standard conversion of 9 kcal/g of fat, we calculated the dietary fat energy supply ratio according to the following formula:

Fat energy ratio =the daily fat intake(g)×9the total daily dietary energy intake(Kcal)[1]

The diagnosis of KS was based on self-reported data from a face-to-face interview questionnaire. During the interviews, the participants were asked “Have you ever had kidney stones?” The participants were classified as suffering from KS or having a history of KS if they gave a positive answer.

Ascertainment of covariates

The covariates considered in this study included demographic details (age, gender, race, marital status, educational levels), body mass index (BMI), smoking, alcohol consumption, diabetes and hypertension prevalence, metabolic syndrome (MetS) and dietary composition (energy, protein, carbohydrate, cholesterol, calcium, phosphorus, magnesium, and potassium intake). According to the WHO standards (14), BMI was converted into a categorical variable, where a BMI <25 kg/m² was considered normal, a BMI ≥25 and <30 kg/m² was considered overweight, and a BMI ≥30 kg/m² was considered obese. In our paper, the energy intake data is in kcal, protein and carbohydrate intake is measured in gram (g), and we use milligram (mg) as the unit of electrolyte intake such as cholesterol, sodium, calcium, magnesium, and phosphorus.

Statistical analysis

Consistent with NHANES analytical guidelines, weighted analyses accounting for the survey’s complex sampling design were conducted to produce nationally representative estimates of the U.S. Weighted categorical variables are presented as percentages, and the survey-weighted mean ± standard deviation (SD) was the formula used for descriptive statistics of continuous data. Several models were employed to adjust for covariates. Adjustment pattern 1 adjusted for sex, age and BMI. Adjustment pattern 2 included additional adjustments for BMI, energy, protein, carbohydrate, cholesterol, calcium, phosphorus, magnesium and potassium intake. Adjustment pattern 3 included all the covariates in adjustment pattern 2 and ethnicity, education levels, marital status, smoking, alcohol consumption, diabetes, hypertension and MetS. Subgroup analyses were used to further explore the association between HFD and KS among the different groups. R software (version 4.4.1) was used to conduct all the statistical analyses in our research. A P value <0.05 indicated statistical significance.

Results

Baseline characteristics of study participants

In total, 31,059 American participants were included in the weighted analysis. As shown in Table 1, individuals with KS were more frequently male (55.69%, 1,672/3,003), older in age, and of White ethnicity (75.68%, 1,633/3,003), though no significant difference was detected in educational attainment between the groups. The KS group exhibited a higher BMI and a greater prevalence of diabetes, hypertension, and MetS compared to the non-KS group. While smoking status did not differ significantly between groups, alcohol consumption was less common among KS individuals. Dietary assessment indicated a higher proportion of HFD consumption in the KS group, accompanied by lower intake of magnesium and phosphorus, with no other significant differences observed in the remaining nutrients. When participants were categorized by dietary pattern (Table 2), the HFD group tended to be older, have a higher proportion of White individuals, higher education levels, higher marriage rates, elevated BMI, and increased prevalence of KS, diabetes, hypertension, and MetS. Additionally, significant differences were found in the intake of various nutrients between the two dietary groups.

Association between HFD and KS

The relationship between HFD and KS was analysed through several different regression models (Table 3). In the unadjusted model, HFD was positively associated with a high risk of KS [odds ratio (OR) =1.19, 95% confidence interval (CI): 1.05–1.35, P=0.007]. This relationship remained significant in adjustment pattern 1, which accounted for sex and age (OR =1.16, 95% CI: 1.02–1.32, P=0.03). After additional adjustment for BMI, energy, protein, carbohydrate, cholesterol, calcium, phosphorus, magnesium and potassium intake, adjustment pattern 2 still suggested that HFD increased the risk of KS (OR =1.24, 95% CI: 1.08–1.44, P=0.003). This relationship persisted in the fully adjusted model 3, which further adjusted for ethnicity, education levels, marital status, smoking, alcohol consumption, diabetes, hypertension and MetS (OR =1.23, 95% CI: 1.06–1.42, P=0.008).

Subgroup analysis

Subgroup analyses were conducted to assess the association between HFD and the risk of KS across sex, age, and BMI categories (Figure 2). The association was more pronounced in males (OR =1.30, 95% CI: 1.10–1.54) than in females (OR =1.07, 95% CI: 0.89–1.30). Age-stratified analysis indicated no significant association between HFD and KS in either the older (OR =1.19, 95% CI: 0.96–1.46) or the younger group (OR =1.16, 95% CI: 0.97–1.38). BMI-based stratification revealed a trend toward increased KS risk in the mild BMI group (OR =1.24, 95% CI: 0.98–1.58), while no significant association was observed in the low (OR =0.99, 95% CI: 0.77–1.27) or high BMI groups (OR =1.18, 95% CI: 0.99–1.41). Notably, no significant interaction effects were detected across any of these subgroups (all P for interaction > 0.05).

Figure 2 Subgroup analysis for the association between HFD and kidney stones. BMI, body mass index; CI, confidence interval; HFD, high fat diet; OR, odds ratio.

Discussion

The global obesity rate is expected to increase to 21% for women and 18% for men by 2025, which reflects the fact that the consumption of HFD has become widespread due to economic development (15). However, studies on variations in the prevalence of KS caused by changes in dietary patterns are relatively rare. This cross-sectional study explored the relationship between HFD and KS, revealing a positive association between the consumption of HFD and an increased incidence of KS. These findings offer new insights into the risk factors for KS and contribute to the development of strategies for its prevention.

HFD usually refers to a dietary pattern with a high proportion of fats, especially saturated fats and trans fats, and the consumption of HFD is closely linked with the presence of cardiovascular diseases, obesity, diabetes and other chronic diseases (16-18). Current research indicates that HFD is associated with the progression of diseases such as obesity and MetS, both of which are strongly linked to the onset and recurrence of KS (19-21). MetS, characterized by a cluster of metabolic abnormalities such as hypertension, hyperglycemia, central obesity, elevated triglyceride (TG) levels, and reduced high-density lipoprotein cholesterol (HDL-C) levels, has been strongly associated with an increased risk of KS formation (22). Specifically, hypertriglyceridemia and low HDL-C levels are thought to contribute to stone formation through several mechanisms. Elevated TG levels may lead to increased urinary excretion of calcium, oxalate, and uric acid, promoting supersaturation and subsequent stone formation (23). Additionally, low HDL-C levels are often linked to insulin resistance, which impairs renal calcium handling and enhances urinary calcium excretion, further increasing the risk of stone development (24). A recent study demonstrated a significant association between hypertriglyceridemia, a high cholesterol-to-HDL ratio, and KS (25). Participants with hypertriglyceridemia (67–93 mg/dL) had a 1.463-fold increased risk of developing KS, while higher HDL-C levels (>63 mg/dL) appeared protective against stone formation. These findings underscore the role of lipid metabolism in the pathogenesis of KSs. Central obesity increases the risk of KS by affecting serum calcium concentrations. This effect may be attributed to the transcriptional and adipokine profiles of visceral adipose deposits influencing calcium homeostatic pathways (26).

Several observational studies have revealed a strong association between KS and systemic inflammation, and an antioxidant diet may help reduce the risk of KS (27,28). HFD promotes the progression of low-grade systemic inflammation by contributing to intestinal barrier dysfunction and the entry of toxic bacterial metabolites into the circulation, ultimately causing a range of pathophysiological changes (29). Zhang and colleagues reported that HFD influences serum levels of adipokines and cytokines, leading to elevated levels of inflammatory factors, such as TNF-α, IL-6, and CXCL10 (30). Studies have shown that the renal tissue surrounding Randall’s plaque, which is considered the initial site of KS development, is related to the activation of proinflammatory macrophages (M1) and the downregulation of anti-inflammatory macrophages (M2) (31). Thus, HFD may contribute to the development of KS by inducing a systemic low-grade inflammatory response.

Gut microorganisms play important roles in HFD-related diseases. Intestinal dysbiosis is involved in the development and progression of KS, particularly calcium oxalate stones (32). Oxalate, the major component of stones in 75% of KS patients, is influenced by the gut microbiota via effects on oxalate homeostasis (33,34). Intestinal bacteria may alter oxalate metabolism and increase oxalate secretion by intestinal epithelial cells (35).

In this study, the stone group showed less magnesium intake than the non-stone group, which may suggest that higher magnesium intake may play a preventive role in KS survival. Shringi et al. conducted correlation and regression analysis of dietary magnesium data in NHANES data, and the results and hypothesis were consistent with our study (36). Our team previously conducted an umbrella review of multitudinous literature studies based on the risk factors for the development of KS, which also found that dietary magnesium has a protective effect on KS (11). Based on our paper, the high-fat diet group showed higher levels of magnesium intake, which may be related to the fact that foods rich in magnesium are often rich in fat, such as nuts, dark chocolate, etc. However, the specific mechanism is still unclear, and more studies on magnesium and KS are still to be carried out.

There are several limitations of our study. First, there is no universal definition of HFD. Therefore, we defined HFD as a daily fat energy ratio exceeding 30%. However, HFD is regarded as a diet in which the daily fat energy ratio exceeds 50% or more of the total caloric intake in some clinical studies (37-39). Second, the dietary data for each participant were collected through 24-hour dietary recall interviews. Twenty-four-hour dietary recalls are associated with underreporting of energy intake, and the underreporting bias in energy intake is proportionally related to total energy intake (40). But the degree of such underreporting was substantially lower than that observed with other dietary intake assessment tools (41). Due to a large volume of missing dietary data, our study only included the first dietary recall interview, which may introduce potential self-reporting bias. And owing to the intrinsic limitations of cross-sectional studies, our findings cannot establish a causal relationship between HFD and KS. This relationship may need to be validated through further research, such as Mendelian randomization studies. Additionally, since both exposure and outcome variables were self-reported, the risk of self-report and recall bias exists, which could result in the underreporting of asymptomatic KS cases. Larger, well-designed clinical trials may be necessary in the future to explore the causal relationship between HFD and KS.

Conclusions

Our study indicated that HFD increases the risk of KS development. This study provides new ideas for the subsequent prevention of KS formation via dietary control. However, it is still necessary to verify the causal relationship between HFD and KS in more prospective studies.

Acknowledgments

We sincerely thank all those who participated in the NHANES study.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-333/rc

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-333/prf

Funding: This study was supported by the Foundation of Science & Technology of Sichuan Province (No. 2023YFS0029) and Scientific Research Fund of the Administration of Traditional Chinese Medicine of Sichuan Province (No. 2023MS092).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-333/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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