Abstract
Background and Aims
Patients undergoing dialysis for end-stage kidney disease (ESKD) have poorer nutritional status than the general population, and worse nutritional status is associated with poor clinical outcomes. Hyperphosphatemia is common in dialysis patients owing to abnormal mineral and bone metabolism. Nephrologists manage hyperphosphatemia by prescribing phosphate binders and/or recommending restriction of dietary protein intake; the latter may, however, adversely affect nutritional status. In this analysis, we address the hypothesis that, even in the presence of hyperphosphatemia, liberalizing dietary protein leads to better patient outcomes.
Method
The analysis includes 11,628 hemodialysis (HD) patients in 12 countries in DOPPS phase 4 (2009-2011), from 254 facilities where the medical director completed a survey reporting facility practices. Demographic data, comorbid conditions, laboratory values, and medications were abstracted from patient records. Mortality was assessed during study follow-up. The primary exposure variable was response to the following question: “For patients with serum albumin 3.0 g/dL and phosphate 6.0 mg/dL, do you typically recommend to (A) increase or (B) not change or decrease dietary protein intake?” The primary outcome was all-cause mortality, analyzed by Cox regression, stratified by country, accounting for facility clustering using robust sandwich covariance estimators, and adjusted for case-mix and laboratory values. Linear regression was used to model the associations between the exposure variable and intermediate nutritional markers including serum albumin, creatinine, and phosphorus. We used multiple imputation to replace missing values for model covariates.
Results
Median follow-up was 1.4 years. In the case scenario, 91% of medical directors in North America recommended to increase protein intake compared to 58% in Europe (range=36-83% across 7 countries) and 56% in Japan (Figure). Advice to increase dietary protein intake was associated with 0.33 mg/dL higher serum creatinine levels (95% CI: 0.08-0.57) after adjustment for case mix, while clinically meaningful associations were not observed for serum albumin and phosphorus. Advice to increase dietary protein intake was weakly associated with lower mortality [HR (95% CI): 0.89 (0.77-1.03)]. The association with survival was stronger in patients with age 70+ years [HR (95% CI): 0.81(0.68-0.96), P=0.08 for interaction] and for those without diabetes [HR (95% CI): 0.81(0.66-0.98), P=0.20 for interaction]
Conclusion
In this large international cohort study, the medical director’s stated preference to recommend an increase in dietary protein intake for HD patients with low albumin and high phosphorus levels was most common in North America and was associated with higher patient serum creatinine levels and potentially lower all-cause mortality. Additional research into the possible benefits of protein intake liberalization for HD patients, even in the presence of hyperphosphatemia, is warranted.
This abstract was directly supported by Kyowa Kirin Co.,Ltd..
Inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients
