Non-linear associations between serum manganese with chronic kidney disease: results from two nationwide studies in the United States and China

This study aimed to better evaluate the association between serum manganese (Mn) and chronic kidney disease (CKD) by using data from the United States National Health and Nutrition Examination Survey (NHANES) and the Chinese Longitudinal Healthy Longevity Study (CLHLS). A total of 15411 and 451 participants were selected from NHANES and CLHLS, respectively. The primary diagnosis of CKD was defined as eGFR <60 mL/min/1.73 m² and urinary albumin-creatinine-ratio (ACR) ≥30 mg/g. Multivariable regression and threshold analyses were used to assess the associations between Mn level and CKD. The prevalence of CKD was estimated to be 8.1% in NHANES and 47.7% in CLHLS. After adjusting for covariates, participants with the highest quartile (Q4) of Mn had an increased likelihood of CKD than those with Q1 (OR = 0.69, 95% CI 0.56–0.84 in NHANES, and OR = 0.32, 95% CI 0.17–0.59 in CLHLS). The non-linear associations revealed that the OR values of CKD were decreased with Mn before reaching the threshold (OR = 0.65 per 1 μg/L increase of Mn in NHANES and 0.98 in CLHLS). Beyond the threshold, further increases in Mn levels were no longer associated with a statistically significant protective effect against CKD risk. This association remained robust by using the continuity of eGFR and ACR as the outcome. Exploration analysis showed that superoxide dismutase (SOD) mediated 6.7% of the effect of Mn levels on CKD. The higher Mn concentration was significantly associated with a lower prevalence of CKD through different non-linear patterns.