Original Investigation
Dialysis
Phosphate Binder Use and Mortality Among Hemodialysis Patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS): Evaluation of Possible Confounding by Nutritional Status

https://doi.org/10.1053/j.ajkd.2011.12.025Get rights and content

Background

Poor nutritional status and both hyper- and hypophosphatemia are associated with increased mortality in maintenance hemodialysis (HD) patients. We assessed associations of phosphate binder prescription with survival and indicators of nutritional status in maintenance HD patients.

Study Design

Prospective cohort study (DOPPS [Dialysis Outcomes and Practice Patterns Study]), 1996-2008.

Setting & Participants

23,898 maintenance HD patients at 923 facilities in 12 countries.

Predictors

Patient-level phosphate binder prescription and case-mix–adjusted facility percentage of phosphate binder prescription using an instrumental-variable analysis.

Outcome

All-cause mortality.

Results

Overall, 88% of patients were prescribed phosphate binders. Distributions of age, comorbid conditions, and other characteristics showed small differences between facilities with higher and lower percentages of phosphate binder prescription. Patient-level phosphate binder prescription was associated strongly at baseline with indicators of better nutrition, ie, higher values for serum creatinine, albumin, normalized protein catabolic rate, and body mass index and absence of cachectic appearance. Overall, patients prescribed phosphate binders had 25% lower mortality (HR, 0.75; 95% CI, 0.68-0.83) when adjusted for serum phosphorus level and other covariates; further adjustment for nutritional indicators attenuated this association (HR, 0.88; 95% CI, 0.80-0.97). However, this inverse association was observed for only patients with serum phosphorus levels ≥3.5 mg/dL. In the instrumental-variable analysis, case-mix–adjusted facility percentage of phosphate binder prescription (range, 23%-100%) was associated positively with better nutritional status and inversely with mortality (HR for 10% more phosphate binders, 0.93; 95% CI, 0.89-0.96). Further adjustment for nutritional indicators reduced this association to an HR of 0.95 (95% CI, 0.92-0.99).

Limitations

Results were based on phosphate binder prescription; phosphate binder and nutritional data were cross-sectional; dietary restriction was not assessed; observational design limits causal inference due to possible residual confounding.

Conclusions

Longer survival and better nutritional status were observed for maintenance HD patients prescribed phosphate binders and in facilities with a greater percentage of phosphate binder prescription. Understanding the mechanisms for explaining this effect and ruling out possible residual confounding require additional research.

Section snippets

Data Source

Data were from phases I-III of the DOPPS, an international prospective cohort study in 12 countries.12, 13 The DOPPS is based on nationally representative samples of randomly selected dialysis facilities and patients. Within each participating facility, 20-40 patients were randomly selected, depending on facility size. Institutional review boards in each country approved the study, and informed patient consent was obtained in accordance with local requirements.

The main analyses were based on

Patient Characteristics by Phosphate Binder Prescription

Patient characteristics by phosphate binder prescription and ORs for phosphate binder prescription by patient characteristic are listed in Table 1 for the 23,898 maintenance HD patients receiving HD for at least 90 days at study entry. Patients prescribed phosphate binders represented 88.1% of the sample. Patients prescribed a phosphate binder had a lower prevalence of several comorbid conditions and a profile consistent with better nutritional status for each of the 5 nutritional measures:

Discussion

Results of this large international prospective cohort study indicate greater survival for maintenance HD patients prescribed a phosphate binder and in facilities with a higher percentage of patients with a phosphate binder prescription. Sensitivity analyses suggest a similar survival benefit in prevalent and incident maintenance HD patients. The longer first-year survival associated with phosphate binder prescription in incident maintenance HD patients is consistent with results from a

Acknowledgements

Initial research was presented as an abstract entitled “Phosphate binder use and mortality among hemodialysis (HD) patients in the DOPPS: influence of nutritional adjustment” at Renal Week 2009, October 27-November 1, San Diego, CA.

Support: The DOPPS is administered by Arbor Research Collaborative for Health and is supported by scientific research grants from Amgen (since 1996), Kyowa Hakko Kirin (since 1999, in Japan), Sanofi/Genzyme (since 2009), Abbott (since 2009), Baxter (since 2011), and

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    Originally published online March 5, 2012.

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