Kidney stones are a very prevalent disease worldwide, with severe pain as the main symptom and a worldwide prevalence of 14.8% [1]. The prevalence of kidney stones among men in the United States is 10.6%, compared to 7.1% among women [2]. Dietary and lifestyle factors are strongly associated with kidney stones [3]. Higher consumption of tea, legumes, and fermented vinegar is associated with a reduced risk of kidney stone formation [4]. The beneficial effect of tea on kidney stones may be mainly due to the diuretic effect of a high intake of caffeine and the action of components with antioxidant properties [5]. Legumes may increase urine volume and improve urine biochemical parameters such as oxalic acid and uric acid levels, which may inhibit the aggregation and progression of crystals in the urine [6, 7]. Fermented vinegar is an alkaline food that increases urine pH and citrate excretion, which may be the potential to reduce kidney stones [8, 9]. The increasing high prevalence of kidney stones enhances the economic burden on society [10].
Lead is one of the most common toxic heavy metals, and most lead-exposure mixtures come from a wide range of industrial products, including ceramics, paints, solder, and batteries [11]. Lead exposure routes also include some water sources and foods such as seafood and meat [12]. In addition, people's poor lifestyles such as smoking are also closely associated with lead exposure, and significantly elevated lead concentrations were found in blood and lung tissue samples from smokers [13–15]. Lead poisoning is a major public health problem worldwide, and studies have indicated that lead toxicity can damage the human central nervous system and affect neurocognitive and behavioral development [16]. Lead poisoning can promote oxidative stress and inflammation, alter vascular endothelial function, and disrupt vascular smooth muscle Ca2 + signaling, leading to atherosclerosis and various cardiovascular diseases [17]. One study indicated that an increase in blood lead concentration from 1.0 µg/dL to 6.7 µg/dL was associated with all-cause mortality, cardiovascular disease mortality, and ischemic heart disease mortality [18]. Oxidative stress has also been implicated as a cause of nephrotoxicity from lead exposure [19].
A study on the non-occupational population in Nandan of China showed that high blood lead exposure was significantly associated with higher kidney stone risk in males [20]. However, in another study, blood lead levels were observed to be associated with a reduced incidence of kidney stones in men and non-Hispanic whites [21]. As there are few epidemiological studies on lead exposure and kidney stones, and the results are conflicting. Urine lead measurements reflected lead diffused from plasma and excreted through the kidneys, and these measurements are useful for long-term biomonitoring.Therefore, our study analyzed data from NHANES 2007–2020 to investigate the association between urinary lead levels and kidney stones. We hypothesized that urinary lead exposure showed a positive association with the risk of kidney stones.
Materials and Methods
1.1 Study Population
We obtained data from NHANES, a study with the primary purpose of assessing the health and nutritional status of the U.S. population, which was administered by the National Center for Health Statistics (NCHS) and approved by the NCHS Ethics Review Board, with all participants signing the informed consent form. The data sample included in NHANES is representative due to the complex stratified multilevel probability sampling method used in the study design. NHANES mainly includes demographic data, physical examinations, laboratory tests, prescribed medications, and health-related questionnaires. All NHANES data are publicly available at https://www.cdc.gov/nchs/nhanes/.
Our study was based on seven NHANES survey cycles from 2007 to 2018, during which data on both kidney stones and urinary lead levels were included. We initially included 75,402 participants, excluding individuals under 18 years of age (n = 29,129), lacking urinary lead data (n = 37517) and kidney stone data (n = 431), and ultimately 8325 participants were included in our final analysis.
1.2 Exposure and Outcome Definitions
Urinary lead levels (ULL) were designed as an exposure variable. For the determination of urine lead concentration, if the test result is below the lower limit of detection (LLOD), the value is LLOD divided by the square root of 2.
The primary outcome of the analysis was the answer to the question, "Have you ever had kidney stones ?" We considered any subject who reported passing at least one stone to have a history of symptomatic stones.
1.3 Measurement of urine lead
The Division of Laboratory Sciences, National Center for Environmental Health, and Centers for Disease Control and Prevention in Atlanta, Georgia, Georgia, used inductively coupled plasma dynamic reaction cell-mass spectrometry to accurately measure lead concentrations in urine (ICS-MS) [14]. All QC procedures recommended by the manufacturers were followed.
1.4. Covariates
Potential covariates that might confound the association between urinary lead concentrations and kidney stones were summarized in the multivariable-adjusted models. The variables in our study included age, gender, race, education level, the ratio of income to poverty (PIR), body mass index (BMI), serum creatinine, serum uric acid, total cholesterol, triglycerides, urinary albumin to creatinine ratio (ACR), elevated glomerular filtration rate (eGFR), total water intake, intakes of calcium, phosphorus, magnesium, sodium and potassium, hypertension, diabetes, smoking, and alcohol consumption status. Hypertension was defined based on a self-reported diagnosis of hypertension, diastolic blood pressure ≥ 90 mmHg or systolic blood pressure ≥ 140 mmHg, or the use of antihypertensive medications [22]. Diabetes mellitus was defined based on a self-reported diagnosis of diabetes mellitus, 2-h plasma glucose ≥ 200 mg/dL in an oral glucose tolerance test, HbAlc ≥ 6.5%, use of oral hypoglycemic agents, or fasting glucose ≥ 126 mg/dL [23]. BMI was categorized as < 25, 25-29.9, and ≥ 30 kg/m2, which corresponded to the normal weight, overweight and obese population of participants. All detailed measurement processes of these variables are publicly available at www.cdc.gov/nchs/nhanes/.
1.5. Statistical Analysis
All statistical analyses were performed according to Centers for Disease Control and Prevention (CDC) guidelines with appropriate NHANES sampling weights and a complex multistage cluster survey design illustrated in the analysis. Continuous variables were expressed as means and standard errors, and categorical variables were expressed as percentages. Differences between groups by urinary lead level (quartiles) were assessed using a weighted Student's t-test (continuous variables) or a weighted chi-square test (categorical variables). Multivariate logistic regression models were used to explore the independent relationship between urinary lead levels and kidney stones in three different models. No covariates were adjusted for in Model 1, and in Model 2, age, gender, and race were adjusted. In Model 3, adjustments were made for age, sex, race, education level, PIR, BMI, serum creatinine, serum uric acid, total cholesterol, triglycerides, ACR, eGFR, total water intake, calcium, phosphorus, magnesium, sodium and potassium intake, hypertension, diabetes mellitus, smoking, and alcohol consumption status. Subgroup analyses stratified by gender, age, BMI, hypertension, diabetes, smoking, and drinking status were also performed by stratified multiple regression analysis, and effect modification in subgroups was examined using interaction terms between subgroup indicators. All analyses were performed using R version 4.2.1 (http://www.R-project.org, The R Foundation), and p < 0.05 was considered statistically significant.