Differences in association between hypoalbuminaemia and mortality among younger versus older patients on haemodialysis

Abstract

Background: Ageing often affects biomarker production. Yet, clinical/optimal thresholds to guide clinical decisions do not consider this. Serum albumin decreases with age, but hypoalbuminaemia is defined as serum albumin <4.0 g/dl. This study explores whether age might affect serum albumin levels and its association with mortality in haemodialysis patients.

Methods: COSMOS (Current Management of Secondary Hyperparathyroidism: a Multicentre Observational Study) is a prospective, open-cohort, observational study of haemodialysis patients followed for 3 years. Binary logistic and linear regression were used to analyse the association between age and hypoalbuminaemia or serum albumin (continuous). Cox proportional hazard multivariate regression was used to examine the relationship between hypoalbuminaemia and mortality in patients younger and older than 65 years. Time-dependent receiver operating characteristic (ROC) curves were used to assess the discriminatory ability of serum albumin and optimal thresholds for predicting mortality.

Results: The present analysis included 5585 patients. The odds of experiencing hypoalbuminaemia increased with age [adjusted odds ratios = 1.56(95%CI: 1.31-1.86), 1.89(95%CI: 1.59-2.24), 2.68(95%CI: 2.22-3.23) for 56-65, 66-75, and >75 years, respectively (reference ≤55 years; P value for trend: <0.001)]. Survival analysis showed that the association between hypoalbuminaemia and mortality was weaker in patients aged ≥65 compared to <65 years [hazard ratios: 1.36(95%CI: 1.17-1.57) and 1.81(95%CI:1.42-2.31) respectively; P value for interaction 0.004]. The ability of albumin levels to predict mortality was consistently higher in younger patients. Optimal albumin thresholds for predicting mortality were 3.7 g/dl in patients younger than 65 years and 3.5 g/dl in patients 65 years and older.

Conclusions: Ageing is accompanied by lower albumin levels, and the association between hypoalbuminaemia and mortality may be modified by age. Different clinical thresholds that consider age may better discriminate risks associated with hypoalbuminaemia.

Keywords: ageing; albumin; chronic kidney disease; haemodialysis; mortality.

Graphical Abstract

Figure 1:

Prevalence of hypoalbuminaemia (serum albumin <4.0 g/dl) across age groups.

Figure 2:

Impact of serum albumin on mortality risk in haemodialysis patients: a restricted cubic spline analysis with age stratification. Hazard ratios and 95% confidence intervals (shaded area) are depicted in the elderly (≥65 years old, n = 3127) and non-elderly (<65 years old, n = 2458) haemodialysis patients. Estimates were adjusted for age, sex, smoke, aetiology of CKD, BMI, diabetes, cardiovascular disease, type of haemodialysis, vintage, PTH, calcium, and phosphate.

Figure 3:

Differential association between hypoalbuminaemia and 3-year mortality risk in non-elderly (<65 years) vs. elderly (≥65 years) haemodialysis patients. Hazard ratios were adjusted for age, sex, smoke, aetiology of CKD, BMI, diabetes, cardiovascular disease, type of haemodialysis, vintage, PTH, calcium, and phosphate.

Figure 4:

Age-dependent predictive ability of baseline serum albumin for mortality at 18 months in haemodialysis patients using time-dependent ROC. The area under the curve (AUC) of the time-dependent ROC curve was consistently higher in patients younger than 65 years throughout all follow-up periods (data not shown). As an example, the ROC curve at 18 months demonstrated that the AUC for predicting 18-month mortality risk using baseline serum albumin levels was significantly higher in patients younger than 65 years (95% confidence intervals do not overlap). Serum albumin levels with the maximum sensitivity and specificity were 3.7 g/dl for patients younger than 65 years and 3.5 g/dl for those aged 65 years and older. TPR: true positive rate, FPR: false positive rate.