A U-Shaped Relationship Between Blood Manganese Levels and Anemia in Patients With CKD: A Cross-Sectional Analysis from National Health and Nutrition Examination Survey 2015 to 2018.
Chunjie Jiang, Junlin Yi, Jiahui Lai, Luona Wen, Xiaoshi Zhong, Rongshao Tan, Yun Liu
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Abstract
Rationale & objective: A complex relationship exists between blood manganese (Mn) and hemoglobin concentrations in patients with chronic kidney disease (CKD), with associations observed in patients not treated with dialysis and those on maintenance hemodialysis. This study aimed to elucidate this relationship using a large sample of adult patients with CKD from the National Health and Nutrition Examination Survey (NHANES) database.
Study design: This was a across-sectional study.
Setting & study populations: We included data of 1,016 adult patients with CKD from the NHANES database between 2015 and 2018.
Exposure: We included participants with CKD who were aged ≥18 years, not pregnant, and had available data on hemoglobin, Mn levels, and other relevant covariates.
Outcomes: Hemoglobin and blood Mn levels in patients with CKD.
Analytical approach: Whole-blood Mn concentrations were analyzed using quadrupole inductively coupled plasma mass spectrometry. The statistical analyses included univariate and multivariate linear and binary logistic regression models, along with generalized additive models and smooth curve fitting to explore nonlinearity, which was further examined using a 2-piece-wise linear regression model.
Results: After adjusting for age; sex; race/ethnicity; body mass index; smoking status; and levels of albumin, creatinine, ferritin, and transferrin receptor, a nonlinear (U-shaped) association was observed between Mn levels and anemia risk (P < 0.001 for nonlinearity). Specifically, lower Mn levels (<194.2 nmol/L) were negatively associated with anemia (OR, 0.984; 95% CI, 0.979-0.990; P < 0.001), whereas higher Mn levels (>194.2 μmol/L) showed a positive association (OR, 1.006; 95% CI, 1.001-1.011; P = 0.021).
Limitations: Even with multivariate model analysis, we failed to establish a causal relationship between Mn levels and anemia in patients with CKD.
Conclusions: These findings suggest that Mn may have a dual role in the pathophysiology of anemia in patients with CKD.
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