Magnesium, the fourth most abundant mineral and the second most abundant intracellular divalent cation, is an essential macronutrient for the human body Takaya et al., Jun 2004, Volpe, May 1 2013. Magnesium plays a role in more than 600 enzyme reactions in the human body, including muscle contraction, nerve transmission and cardiac excitability, regulating blood pressure and maintaining the immune system and insulin metabolism Takaya et al., Jun 2004, Volpe, May 1 2013, Guerrero-Romero and Rodríguez-Morán, 2000, de Baaij et al., 2015, Guerrero-Romero et al., 2016. Magnesium ions are essential in maintaining the anatomical and functional integrity of various organelles, including mitochondria and ribosomes [6]. Magnesium activates a variety of enzymes, aids in energy production, and helps regulate levels of calcium, copper, zinc, potassium, vitamin D, and other important nutrients in the body. Additionally, this mineral helps in the formation of teeth and bones [7].

The status of magnesium in the human body is closely related to many diseases. Hypomagnesemia is clinically defined as a serum magnesium concentration <0.75 mmol/L [8], with early nonspecific symptoms including loss of appetite, nausea, vomiting, fatigue, and lethargy. After significant magnesium deficiency occurs, patients often present with increased neuromuscular excitability, cardiac arrhythmias, pregnancy complications, osteoporosis, and impaired motor function [8]. In recent years, more and more studies have found that magnesium deficiency is associated with oxidative stress, cardiovascular disease, cognitive impairment and metabolic syndrome Maier et al., May 24 2004, Dominguez et al., Dec 31 2020, Resnick et al., Oct 1984, Glick, Mar 1990, Yamanaka et al., Jul 12 2019, Mazur et al., Feb 1 2007. Some researches proposed that low extracellular Mg2+ slows down endothelial cell proliferation, stimulates monocyte adhesion, significantly damages endothelial function, affects vascular structure and function, and stimulates atherosclerosis formation Baldoli et al., 2013, Kostov and Halacheva, Jun 11 2018. Moreover, there is a correlation between the amount of serum magnesium and the formation of kidney stone disease (KSD). Subjects with relatively low serum magnesium levels, even within the normal range, have a higher prevalence of kidney stones [17]. Some researchers have reported that increasing serum magnesium levels through dietary intake can prevent vascular calcification in Klotho knockout mice [18], and klotho has been shown to be a risk factor for kidney stone formation Telci et al., 2011, Xiao and Xiao, 2023, Lanka et al., 2021.

Kidney stones as the most common type of urolithiasis had an increasing prevalence over the past decades, placing high costs and clinical burdens on the healthcare system [22]. In the United States, the prevalence of kidney stones gradually increased from 3.2% from 1976 to 1980–8.8% in 2010, which means that the prevalence of kidney stones has increased nearly three times in the past 30 years [23]. In addition, epidemiological statistics from Italy, Germany, Japan and other countries Trinchieri et al., Jan 2000, Hesse et al., Dec 2003, Yasui et al., Feb 2008 show that at the end of the 20th century, the prevalence of kidney stones increased to varying degrees in different regions. Many metallic elements are closely linked to the mechanisms of stone formation [27]. Approximately 80% of kidney stones are composed of calcium oxalate (CaOx) mixed with calcium phosphate (CaP), others composed of uric acid, struvite, and cystine are also common, accounting for approximately 9%, 10%, and 1% of stones respectively [28]. In the intestine and urine, magnesium and calcium compete for binding to oxalic acid. However, compared to calcium oxalate, which is more difficult to dissolve in water, magnesium oxalate is not as prone to stone formation at normal physiological concentrations in urine. Magnesium can also bind oxalates in the gastrointestinal tract and reduce their absorption. Through different mechanisms, a low magnesium state leads to poor urinary magnesium excretion and leads to urinary calcium oxalate supersaturation with an increased likelihood of formation of insoluble complexes [29]. In previous literature, kidney stone formation has generally been associated with sex hormones, especially testosterone Huang et al., 2022, Changtong et al., 2016, Fuster et al., 2022, Fedrigon et al., 2019. It has recently been reported that women with polycystic ovary syndrome (PCOS), particularly those who present with irregular menstruation and polycystic ovary morphology (PCOM) on ultrasound, have a higher likelihood of developing kidney stones [34].

Magnesium homeostasis is maintained by the intestines, bones, and kidneys. After daily intake of magnesium, only about 24–76% is absorbed by the small intestine and stored in the bones, and excess magnesium is excreted by the kidneys and intestines [35]. Under physiological conditions, about 2400 mg of magnesium in plasma is filtered by the glomeruli of kidney [36]. Of the filtered load, 95% magnesium is immediately reabsorbed and only 3–5% is excreted in the urine [37]. Intestinal absorption is not directly proportional to magnesium intake, but mainly depends on magnesium status. When serum magnesium levels are lower, the intestine absorbs more of this element, so when intake is low, the relative absorption of magnesium is high [38]. Since most magnesium is stored in cells and bones, it is difficult to accurately assess magnesium status in the human body. Currently, serum magnesium testing is fast and convenient and remains the standard commonly used to assess human magnesium status in clinical and research settings. In order to evaluate the status of magnesium in the body from more dimensions, magnesium depletion score (MDS) is introduced for further study.

Fan et al. developed the MDS, a composite score aggregating 4 established risk factors, which also considers the pathophysiological factors influencing the kidneys’ reabsorption capability [39]. The developed model of MDS, coupled with sex and age, may serve as a promising measure to identify magnesium deficiency and systemic inflammation and predict risk of CVD mortality and chronic disease.

However, to our knowledge, the association between the MDS and stone formation has not been studied. This study aimed to investigate whether MDS is an independent determinant for the presence of KSD by examining data from a nationally representative sample of adults.