Interactions Between Malnutrition, Inflammation, and Fluid Overload and Their Associations With Survival in Prevalent Hemodialysis Patients

Objective: Predialysis fluid overload (FO) in hemodialysis (HD) patients is associated with an increased risk of death, further increased by the presence of inflammation. Malnutrition is also associated with outcome. Study objectives were, firstly, to investigate if the presence of FO is associated with malnutrition and whether this association is influenced by the presence of inflammation. Second, we assessed the associations of FO, malnutrition, and inflammation with outcome individually and in combination.

Design: International cohort study.

Setting: European patients of the Monitoring Dialysis Outcome Initiative cohort where bioimpedance and C-reactive protein measurements are performed as standard of care.

Subjects: 8883 prevalent HD patients.

Main Outcome Measure: Body composition, nutritional and inflammation status were assessed during a 3-month baseline period, and all-cause mortality was noted during 1 year follow-up. Malnutrition was defined as a lean tissue index <10th percentile (of age and gender matched healthy controls), FO as a predialysis overhydration >+1.1 L and inflammation as a C-reactive protein > 6.0 mg/L. We used Cox models to investigate the association with outcome.

Results: The presence of malnutrition was associated with higher levels of FO, this amount further increased when inflammation was present. Only 11.6% of the patients did not have any of the 3 risk factors and only 6.5% of the patients were only malnourished, which was not associated with an increased risk of death (Hazard Ratio [HR] 1.22 [95% Confidence Interval [CI]: 0.75-1.97]), whereas the combination of severe malnutrition, FO, and inflammation comprised the highest risk of death (HR 5.89 [95% CI: 2.28-8.01]).

Conclusion: In HD patients, predialysis FO associates with both malnutrition and the presence of inflammation, with the highest levels of FO observed when both are present. Malnutrition as singular risk factor was not associated with increased mortality risk. The highest mortality risk was observed in patients where all 3 risk factors were present.