Introduction

Chronic kidney disease (CKD) is an increasing and leading public health challenge worldwide, as the primary contributor to global mortality and morbidity [1]. Nearly 10% of adults worldwide suffer from CKD, resulting in nearly 35.0 million years of healthy life lost and 1.2 million deaths every year [45]，then this relationship was weakened [46].

The relevant mechanisms underlying the similar “J”-shaped relationships between serum Mg concentrations and CKD remain incompletely clear, and several possibilities could be proposed to decipher our findings. Firstly, Mg may involve the prevention of nephrocalcinosis, inhibition of phosphate-mediated apoptosis of tubular cells and calcification of renal arteries, and suppression of tubular calcium phosphate crystallization, which may protect against phosphate-induced kidney damage. In addition, tubular dysfunction and interstitial fibrosis could contribute to the loss of Mg [47, 48]. Moreover, matured calciprotein particles have the capacity to induce vascular calcification, and recent studies have shown that Mg could prevent the maturation of calciprotein particles [49], and these may be the basics that underlie the anti-calcification properties of Mg. Secondly, Mg exercises the functions of protein metabolism and energy synthesis. Therefore, Mg deficiency may induce the development of CKD by reducing protein synthesis and energy metabolism of renal reparative cells. Thirdly, the concentrations of antioxidants (e.g., selenium and vitamin C) are decreased in the context of Mg deficiency [50], which was closely related to promoting oxidative stress. In addition, related studies conducted in vitro on endothelial cells have shown that a low Mg medium promotes inflammation and oxidative stress, and induces the expression of proatherothrombotic molecules such plasminogen activator inhibitor-1 and vascular cell adhesion molecule-1 [51], and Mg deficiency was found to be linked to endothelial dysfunction [52], therefore, we reasonably speculate that Mg may have protective effects on endothelium, and Mg deficiency could be responsible for endothelial dysfunction and vascular sclerosis of renal vessels, accelerating the progression of kidney damage. Finally, previous studies also have shown that chronic inflammation is crucial to the development of CKD [53, 54], thus abnormal Mg levels (deficiencies or excesses) may aggravate inflammation-related renal injury.

The large sample size and population-based design of our study were its major strengths, allowing us to perform a series of stratifications and the results were reliable and generalizable to the general population in China. However, our research has certain limitations as well. First, we were unable to establish the causal link between serum Mg and CKD because of the cross-sectional nature of this study. It is still needed to affirm whether the reduced renal function is a crucial risk element for hypermagnesemia or not, maybe the hypermagnesemia results in the faster development of CKD or the compensatory protective elevation of serum Mg for delaying the progression of CKD. Secondly, serum Mg concentrations were assessed at a single time point, thus the measured data may not be objective to reflect the whole life-course activity, and there is no more relevant available data on Mg intake in this database, so we cannot conduct subsequent causal analyses. Thirdly, due to a lack of data on the severity of CKD, we could not determine whether these associations differed by the severity of CKD; while the prevalence of CKD in our study is comparable to that estimated in global analysis (8.0–16.0%) [55]. Finally, although we have considered several potential confounders, including various lifestyles and dietary variables, additional unmeasured confounders cannot be fully excluded.

Conclusions

In this relatively large-scale, national study, we found a similar “J”-shaped association between serum Mg concentrations and CKD among Chinese adults. Our findings highlight the possibility of maintaining the optimal serum Mg concentrations for the management of CKD, and present the feasibility that Mg might be an intervention target for the treatment of CKD.