Interaction of Time-Varying Albumin and Phosphorus on Mortality in Incident Dialysis Patients

Abstract

SummaryBackground and objectives Hypoalbuminemia and hyperphosphatemia have been shown to be strong predictors of mortality in dialysis patients that might not be independent from each other. We prospectively investigated the relationship and interaction between serum albumin and phosphorus with all-cause mortality in an inception cohort of incident dialysis patients.Design, setting, participants, & measurements We followed 235 incident dialysis patients in a prospective single-center cohort study (INVOR study) applying a time-dependent Cox proportional hazards model using all measured laboratory values (2887 albumin and 10306 phosphorus values).Results Eighty-two patients (35%) died during a median follow-up of 35.1 months. Albumin was inversely associated with mortality (hazard ratio [95% confidence interval]: 0.23 [0.14 to 0.36]; P Ͻ 0.001), whereas higher phosphorus concentrations showed a trend to an increasing risk for mortality (hazard ratio 1.57 [95% confidence interval 0.97 to 2.54]; P ϭ 0.07). Importantly, we observed a significant interaction between albumin and phosphorus (P ϭ 0.01). The lowest risk was found with concurrent low phosphorus and high albumin values, whereas risk was increased with either concurrent low phosphorus and low albumin values or high phosphorus and high albumin values. ConclusionsIn incident dialysis patients the associations of serum phosphorus and albumin concentrations with mortality are modified by each other over time. Phosphorus-lowering interventions that concomitantly can cause a fall in serum albumin level may be harmful and warrant additional studies. If confirmed, epidemiologic studies and therapeutic guidelines aiming for target values should consider this interplay.

Impact of nutritional index on the association between phosphorus concentrations and mortality in haemodialysis patients: a cohort study from dialysis outcomes and practice pattern study in Japan

“…A recent study in Austria noted statistical multiplicative interactions between time-varying phosphorus and albumin, in which time-varying factors were updated to the most recent values every 3 months 14. Here, we confirmed a statistical multiplicative interaction between time-averaged phosphorus concentration and GNRI on all-cause mortality.…”

“…As nutritional index and phosphorus concentration are linked and may change dramatically overtime, the interaction between time-dependent nutritional index and phosphorus concentration must be carefully considered when evaluating their separate and combined effects on mortality 14. Although the Geriatric Nutritional Risk Index (GNRI)15 was originally intended for use as a screening tool for predicting risk of morbidity and mortality in elderly patients, it has since been validated for use in whole haemodialysis patients 16 17.…”

Visualizing interaction effects: a proposal for presentation and interpretation

“…We have successfully applied one of these approaches in a prospective study on incident dialysis patients, which was very useful for the interpretation of an interaction effect: we observed a significant interaction between time-varying values of albumin and phosphorus on overall mortality in our cohort [13]: for high albumin values, increasing phosphorus concentrations were significantly associated with an increased mortality risk, whereas the beneficial effect of increasing albumin values was only observed for low phosphorus levels. We concluded that decisions about phosphoruslowering therapy should also take albumin values into account and epidemiological studies and guidelines should consider this interplay.…”

Use of Phosphorus Binders among Non-Dialysis Chronic Kidney Disease Patients and Mortality Outcomes

“…Binder patients may reflect those who were more likely to have a liberal diet and therefore improved nutritional status [8,9,16]. Conversely, dietary phosphorus restriction has been shown to be associated with poor nutritional status and greater mortality risk [8,9,39,40]. The lower risk for mortality seen in the phosphorus binder cohort remained significant even after controlling for albumin.…”