Concentrations of Trace Elements and Clinical Outcomes in Hemodialysis Patients: A Prospective Cohort Study

Abstract

Background and objectives: Deficiency of essential trace elements and excess of potentially toxic trace elements are common in patients on hemodialysis. Whether these abnormalities are associated with poor outcomes is unknown but worth investigating, because they are potentially treatable.

Design, setting, participants, & measurements: We did a prospective longitudinal study of 1278 patients on incident hemodialysis, assessing blood concentrations of 25 trace elements at baseline. We used adjusted logistic regression to evaluate the association between trace element status and four outcomes (death, cardiovascular events, systemic infection, and hospitalization). A priori hypotheses concerned (1) deficiency of zinc, selenium, and manganese and (2) excess of lead, arsenic, and mercury. Concentrations of the other 19 elements were tested in hypothesis-generating analyses.

Results: Over 2 years of follow-up, 260 (20%) patients died, 285 (24%) experienced a cardiovascular event, 117 (10%) were hospitalized for systemic infection, and 928 (77%) were hospitalized for any cause. Lower concentrations of zinc or manganese and higher concentrations of lead, arsenic, or mercury were not independently associated with higher risk of clinical outcomes. Lower concentrations of selenium were strongly and independently associated with death (odds ratio, 0.86 per decile; 99.2% confidence interval, 0.80 to 0.93) and all-cause hospitalization (odds ratio, 0.92 per decile; 99.2% confidence interval, 0.86 to 0.98). In exploratory analyses, higher copper concentrations were significantly associated with higher risk of death (odds ratio, 1.07 per decile; 99.2% confidence interval, 1.00 to 1.15), and cadmium levels in the highest decile were associated with higher risk of death (odds ratio, 1.89; 99.2% confidence interval, 1.06 to 3.38).

Conclusions: Lower levels of zinc or manganese and higher concentrations of lead, arsenic, or mercury were not associated with higher risk of clinical outcomes, but lower concentrations of selenium were strongly and independently associated with the risks of death and hospitalization.

Keywords: Arsenic; Cadmium; Copper; Follow-up Studies; Humans; Ions; Lead; Logistic Models; Longitudinal Studies; Manganese; Mercury; Prospective Studies; Selenium; Trace Elements; Zinc; hemodialysis; hospitalization; renal dialysis.

Graphical abstract

Figure 1.

Death at 2 years. Each plot represents one trace element. The markers within each plot represent the deciles of trace elements values of the study population: the first to the last decile from left to right. The blue markers indicate that all or some of the values are less than the fifth percentile of the referent population. Red markers indicate that all or some values are >95th percentile, and green markers indicate that all values are within the fifth to 95th percentiles. The logit of death at 2 years is regressed on each values’ decile as a linear transformation. The black curve is the line of regression. The gray area indicates the 95% confidence limits.

Figure 2.

Cardiovascular events at 2 years. Each plot represents one trace element. The markers within each plot represent the deciles of trace elements values of the study population: the first to the last decile from left to right. The blue markers indicate that all or some of the values are less than the fifth percentile of the referent population. Red markers indicate that all or some values are >95th percentile, and green markers indicate that all values are within the fifth to 95th percentiles. The logit of death at 2 years is regressed on each values’ decile as a linear transformation. The black curve is the line of regression. The gray area indicates the 95% confidence limits.

Figure 3.

Infection events at 2 years. Each plot represents one trace element. The markers within each plot represent the deciles of trace elements values of the study population: the first to the last decile from left to right. The blue markers indicate that all or some of the values are less than the fifth percentile of the referent population. Red markers indicate that all or some values are >95th percentile, and green markers indicate that all values are within the fifth to 95th percentiles. The logit of death at 2 years is regressed on each values’ decile as a linear transformation. The black curve is the line of regression. The gray area indicates the 95% confidence limits.

Figure 4.

Hospitalizations at 2 years. Each plot represents one trace element. The markers within each plot represent the deciles of trace elements values of the study population: the first to the last decile from left to right. The blue markers indicate that all or some of the values are less than the fifth percentile of the referent population. Red markers indicate that all or some values are >95th percentile, and green markers indicate that all values are within the fifth to 95th percentiles. The logit of death at 2 years is regressed on each values’ decile as a linear transformation. The black curve is the line of regression. The gray area indicates the 95% confidence limits.