Revisiting mortality predictability of serum albumin in the dialysis population: time dependency, longitudinal changes and population-attributable fraction

Background. Hypoalbuminaemia is a marker of malnutrition-inflammation complex syndrome (MICS) and a strong predictor of cardiovascular (CV) death in maintenance haemodialysis (MHD) patients. However, serum albumin may change over time. Hence, its time-varying associations with outcome may be different. Methods. Associations between 3-month averaged serum albumin levels, measured in a single laboratory using bromocresol green, and CV mortality were studied longitudinally in a 2-year cohort of 58058 MHD patients. Mortality predictability of fixed baseline and trimonthly-varying serum albumin concentrations were compared. Results. Hazard ratios (HRs) of CV death strictly increased across decrements of baseline serum albumin, whereas the HR for time-varying serum albumin decrements below 3.8g/dl did not differ. A drop in serum albumin in the first 6 months was associated with increasing all-cause and CV death risks in the subsequent 18 months, while a rise in serum albumin was a predictor of better survival independent of baseline serum albumin. The multivariate adjusted population-attributable fraction of death due to baseline serum albumin < 3.8 g/dl was 19 %. Conclusions. Time-varying hypoalbuminaemia predicts all-cause and CV death differently from fixed measures of serum albumin in MHD patients. An increase in serum albumin over time is associated with better survival independent of baseline serum albumin or other MICS surrogates. If this association is causal, an intervention that could increase serum albumin > 3.8 g/dl might reduce the number of MHD deaths in the USA by similar to 10 000 annually. Nutritional interventions examining benefits of increasing serum albumin in MHD patients are urgently needed.