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Aldosterone and mortality in hemodialysis patients: role of volume overload.

Hung SC, Lin YP, Huang HL, Pu HF, Tarng DC - PLoS ONE (2013)

Bottom Line: Elevated aldosterone is associated with increased mortality in the general population.During a median follow-up of 54 months, 83 deaths and 70 cardiovascular events occurred.Cox multivariate analysis showed that by using the low aldosterone as the reference, high aldosterone was inversely associated with decreased hazard ratios for mortality (0.49; 95% confidence interval, 0.25-0.76) and first cardiovascular event (0.70; 95% confidence interval, 0.33-0.78) in the presence of volume overload.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan.

ABSTRACT

Background: Elevated aldosterone is associated with increased mortality in the general population. In patients on dialysis, however, the association is reversed. This paradox may be explained by volume overload, which is associated with lower aldosterone and higher mortality.

Methods: We evaluated the relationship between aldosterone and outcomes in a prospective cohort of 328 hemodialysis patients stratified by the presence or absence of volume overload (defined as extracellular water/total body water >48%, as measured with bioimpedance). Baseline plasma aldosterone was measured before dialysis and categorized as low (<140 pg/mL), middle (140 to 280 pg/mL) and high (>280 pg/mL).

Results: Overall, 36% (n = 119) of the hemodialysis patients had evidence of volume overload. Baseline aldosterone was significantly lower in the presence of volume overload than in its absence. During a median follow-up of 54 months, 83 deaths and 70 cardiovascular events occurred. Cox multivariate analysis showed that by using the low aldosterone as the reference, high aldosterone was inversely associated with decreased hazard ratios for mortality (0.49; 95% confidence interval, 0.25-0.76) and first cardiovascular event (0.70; 95% confidence interval, 0.33-0.78) in the presence of volume overload. In contrast, high aldosterone was associated with an increased risk for mortality (1.97; 95% confidence interval, 1.69-3.75) and first cardiovascular event (2.01; 95% confidence interval, 1.28-4.15) in the absence of volume overload.

Conclusions: The inverse association of aldosterone with adverse outcomes in hemodialysis patients is due to the confounding effect of volume overload. These findings support treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control.

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Volume status for predicting mortality.The receiver operating characteristic (ROC) curve for prediction of all-cause mortality constructed using the ratio of extracellular water to total body water (ECW/TBW) at baseline (A). The optimal cutoff point for ECW/TBW is listed in the attached table, along with the sensitivity, specificity and accuracy for predicting mortality at the end of the follow-up period. The area under ROC curve is significantly larger than 0.5. Kaplan-Meier analysis curve for all-cause mortality in relation to the ECW/TBW at baseline, stratified by the cutoff point among hemodialysis patients (B).
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pone-0057511-g001: Volume status for predicting mortality.The receiver operating characteristic (ROC) curve for prediction of all-cause mortality constructed using the ratio of extracellular water to total body water (ECW/TBW) at baseline (A). The optimal cutoff point for ECW/TBW is listed in the attached table, along with the sensitivity, specificity and accuracy for predicting mortality at the end of the follow-up period. The area under ROC curve is significantly larger than 0.5. Kaplan-Meier analysis curve for all-cause mortality in relation to the ECW/TBW at baseline, stratified by the cutoff point among hemodialysis patients (B).

Mentions: All variables were expressed as percentages for categorical data and as means ± SDs or medians and interquartile ranges (IQRs) for continuous data with or without a normal distribution, respectively. The baseline characteristics of the 2 study subgroups with ECW/TBW ≤48% and >48% were compared using a t-test, x2 statistics, and Mann-Whitney U test as appropriate. Potential differences among the 3 patient groups for each baseline plasma aldosterone tertile were assessed by an analysis of variance (ANOVA), x2 statistics, or the Kruskal-Wallis test, as appropriate. Receiver operating characteristic (ROC) curves were constructed for prediction of mortality using ECW/TBW at baseline. The optimal cutoff point for volume overload (ECW/TBW >48%) is listed in Figure 1, along with the sensitivity, specificity and accuracy for predicting mortality at the end of the follow-up period. Confidence intervals (CI) for the area under the ROC curves were calculated using nonparametric assumptions. Univariate correlations between ECW/TBW or plasma aldosterone and potentially explanatory variables were assessed by Pearson correlation analyses.


Aldosterone and mortality in hemodialysis patients: role of volume overload.

Hung SC, Lin YP, Huang HL, Pu HF, Tarng DC - PLoS ONE (2013)

Volume status for predicting mortality.The receiver operating characteristic (ROC) curve for prediction of all-cause mortality constructed using the ratio of extracellular water to total body water (ECW/TBW) at baseline (A). The optimal cutoff point for ECW/TBW is listed in the attached table, along with the sensitivity, specificity and accuracy for predicting mortality at the end of the follow-up period. The area under ROC curve is significantly larger than 0.5. Kaplan-Meier analysis curve for all-cause mortality in relation to the ECW/TBW at baseline, stratified by the cutoff point among hemodialysis patients (B).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585342&req=5

pone-0057511-g001: Volume status for predicting mortality.The receiver operating characteristic (ROC) curve for prediction of all-cause mortality constructed using the ratio of extracellular water to total body water (ECW/TBW) at baseline (A). The optimal cutoff point for ECW/TBW is listed in the attached table, along with the sensitivity, specificity and accuracy for predicting mortality at the end of the follow-up period. The area under ROC curve is significantly larger than 0.5. Kaplan-Meier analysis curve for all-cause mortality in relation to the ECW/TBW at baseline, stratified by the cutoff point among hemodialysis patients (B).
Mentions: All variables were expressed as percentages for categorical data and as means ± SDs or medians and interquartile ranges (IQRs) for continuous data with or without a normal distribution, respectively. The baseline characteristics of the 2 study subgroups with ECW/TBW ≤48% and >48% were compared using a t-test, x2 statistics, and Mann-Whitney U test as appropriate. Potential differences among the 3 patient groups for each baseline plasma aldosterone tertile were assessed by an analysis of variance (ANOVA), x2 statistics, or the Kruskal-Wallis test, as appropriate. Receiver operating characteristic (ROC) curves were constructed for prediction of mortality using ECW/TBW at baseline. The optimal cutoff point for volume overload (ECW/TBW >48%) is listed in Figure 1, along with the sensitivity, specificity and accuracy for predicting mortality at the end of the follow-up period. Confidence intervals (CI) for the area under the ROC curves were calculated using nonparametric assumptions. Univariate correlations between ECW/TBW or plasma aldosterone and potentially explanatory variables were assessed by Pearson correlation analyses.

Bottom Line: Elevated aldosterone is associated with increased mortality in the general population.During a median follow-up of 54 months, 83 deaths and 70 cardiovascular events occurred.Cox multivariate analysis showed that by using the low aldosterone as the reference, high aldosterone was inversely associated with decreased hazard ratios for mortality (0.49; 95% confidence interval, 0.25-0.76) and first cardiovascular event (0.70; 95% confidence interval, 0.33-0.78) in the presence of volume overload.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan.

ABSTRACT

Background: Elevated aldosterone is associated with increased mortality in the general population. In patients on dialysis, however, the association is reversed. This paradox may be explained by volume overload, which is associated with lower aldosterone and higher mortality.

Methods: We evaluated the relationship between aldosterone and outcomes in a prospective cohort of 328 hemodialysis patients stratified by the presence or absence of volume overload (defined as extracellular water/total body water >48%, as measured with bioimpedance). Baseline plasma aldosterone was measured before dialysis and categorized as low (<140 pg/mL), middle (140 to 280 pg/mL) and high (>280 pg/mL).

Results: Overall, 36% (n = 119) of the hemodialysis patients had evidence of volume overload. Baseline aldosterone was significantly lower in the presence of volume overload than in its absence. During a median follow-up of 54 months, 83 deaths and 70 cardiovascular events occurred. Cox multivariate analysis showed that by using the low aldosterone as the reference, high aldosterone was inversely associated with decreased hazard ratios for mortality (0.49; 95% confidence interval, 0.25-0.76) and first cardiovascular event (0.70; 95% confidence interval, 0.33-0.78) in the presence of volume overload. In contrast, high aldosterone was associated with an increased risk for mortality (1.97; 95% confidence interval, 1.69-3.75) and first cardiovascular event (2.01; 95% confidence interval, 1.28-4.15) in the absence of volume overload.

Conclusions: The inverse association of aldosterone with adverse outcomes in hemodialysis patients is due to the confounding effect of volume overload. These findings support treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control.

Show MeSH
Related in: MedlinePlus