Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Podcasts
    • Subject Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Trainees
    • Peer Review Program
    • Prize Competition
  • About CJASN
    • About CJASN
    • Editorial Team
    • CJASN Impact
    • CJASN Recognitions
  • More
    • Alerts
    • Advertising
    • Feedback
    • Reprint Information
    • Subscriptions
  • ASN Kidney News
  • Other
    • ASN Publications
    • JASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • ASN Publications
    • JASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Podcasts
    • Subject Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Trainees
    • Peer Review Program
    • Prize Competition
  • About CJASN
    • About CJASN
    • Editorial Team
    • CJASN Impact
    • CJASN Recognitions
  • More
    • Alerts
    • Advertising
    • Feedback
    • Reprint Information
    • Subscriptions
  • ASN Kidney News
  • Visit ASN on Facebook
  • Follow CJASN on Twitter
  • CJASN RSS
  • Community Forum
Original ArticlesEpidemiology and Outcomes
You have accessRestricted Access

Prescribed Dietary Phosphate Restriction and Survival among Hemodialysis Patients

Katherine E. Lynch, Rebecca Lynch, Gary C. Curhan and Steven M. Brunelli
CJASN March 2011, 6 (3) 620-629; DOI: https://doi.org/10.2215/CJN.04620510
Katherine E. Lynch
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rebecca Lynch
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gary C. Curhan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steven M. Brunelli
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data Supps
  • Info & Metrics
  • View PDF
Loading

Summary

Background and objectives Hyperphosphatemia is common among hemodialysis patients. Although prescribed dietary phosphate restriction is a recommended therapy, little is known about the long-term effects on survival.

Design, setting, participants, & measurements We conducted a post hoc analysis of data from the Hemodialysis Study (n = 1751). Prescribed dietary phosphate was recorded at baseline and annually thereafter. Marginal structural proportional hazard models were fit to estimate the adjusted association between dietary phosphate restriction and mortality in the setting of time-dependent confounding.

Results At baseline, prescribed daily phosphate was restricted to levels ≤870, 871 to 999, 1000, 1001 to 2000 mg, and not restricted in 300, 314, 307, 297, and 533 participants, respectively. More restrictive prescribed dietary phosphate was associated with poorer indices of nutritional status on baseline analyses and a persistently greater need for nutritional supplementation but not longitudinal changes in caloric or protein intake. On marginal structural analysis, there was a stepwise trend toward greater survival with more liberal phosphate prescription, which reached statistical significance among subjects prescribed 1001 to 2000 mg/d and those with no specified phosphate restriction: hazard ratios (95% CIs) 0.73 (0.54 to 0.97) and 0.71 (0.55 to 0.92), respectively. Subgroup analysis suggested a more pronounced survival benefit of liberal dietary phosphate prescription among nonblacks, participants without hyperphosphatemia, and those not receiving activated vitamin D.

Conclusions Prescribed dietary phosphate restriction is not associated with improved survival among prevalent hemodialysis patients, and increased level of restriction may be associated with greater mortality particularly in some subgroups.

Introduction

Hyperphosphatemia is common among patients with end-stage renal disease. At any time, approximately half of patients on conventional hemodialysis (HD) have serum phosphate above the recommended level (1–4), and nearly all receive additional therapies (beyond HD) to lower phosphate (5). Elevated phosphate contributes to secondary hyperparathyroidism (6,7), elevated FGF23 levels (8,9), and vascular calcification (10–12), which in turn predispose to mortality in this population (13–15). Observational studies have consistently demonstrated a potent and dose-dependent association between higher serum phosphate levels and mortality (1,3,16–18), cardiovascular mortality and morbidity (3,4), and increased rates of hospitalization (14).

Current Kidney Disease Improving Global Outcomes guidelines recommend limiting dietary phosphate intake as a first-line therapy (with or without phosphate binders) for treatment of hyperphosphatemia and secondary hyperparathyroidism (19). However, there has been relatively little study of the effects of long-term dietary phosphate restriction among hemodialysis patients. Prior studies have been of short duration and conducted in highly selected patients and have considered effects only on surrogate end points (e.g. serum phosphate levels), not hard outcomes (20–24). Considering that phosphate-rich foods tend to be good sources of dietary protein (25,26) concern exists that long-term phosphate restriction may exacerbate protein energy malnutrition (27–30), which is both common and potently associated with mortality among hemodialysis patients (31–34).

To add clarity, we conducted a post hoc analysis of the Hemodialysis (HEMO) Study (35), in which we examined the associations between prescribed dietary phosphate (PDP) intake and mortality. The HEMO Study was selected because it is one of the few large-scale, prospective studies among dialysis patients in which dietary prescription was recorded.

Materials and Methods

Study Design

This study was deemed exempt by the Partners Health Care and Beth Israel Deaconess Medical Center Institutional Review Boards. Data for these analyses were taken from the HEMO Study (35) and were made available through the National Institute of Diabetes and Digestive and Kidney Diseases Data Repository. Details of the parent trial have been previously published (36). Briefly, the HEMO study was a randomized controlled trial conducted among 1846 adult patients undergoing thrice-weekly in-center hemodialysis in one of 15 participating centers in the United States and was designed to test the effects of dialysis dose and dialytic membrane flux on clinical outcomes. Patients were enrolled between March 1995 and October 2000, and follow-up continued through December 31, 2001. Notable exclusion criteria included age >80 years, residual urea clearance >1.5 ml/min per 35 L of volume of urea distribution, serum albumin <2.6 g/dl, or serious comorbid medical conditions (end-stage cardiac, pulmonary, or hepatic disease, malignancy, active infection, or unstable angina). We further excluded participants who did not have any dietary prescription recorded at baseline (n = 31) and those who did not survive until the start of at-risk time (n = 64).

Exposures, Outcomes, and Covariates

The primary exposure of interest was PDP, which was recorded at baseline and annually thereafter. Dietary prescriptions were determined by dietitians from the clinical dialysis centers (not study dietitians), except in certain situations (none of which related to phosphate or metabolic bone disease): normalized protein catabolic rate <1 g/kg/d, caloric intake <28 kcal/kg/d, declining serum albumin, or undesired weight loss. In these instances, HEMO Study dietitians initiated dietary counseling to increase protein intake ≥1 g/kg/d and caloric intake to ≥28 kcal/kg/d); if there was no improvement in 1 month, dietary supplements were then recommended.

The outcome considered was all-cause mortality. Each death was reported by the clinical center staff to HEMO investigators, who confirmed the event through review of hospital records, autopsy report, and a narrative summary of events leading up to death.

Demographic covariates included age, sex, race, and dialysis vintage, which were recorded at baseline (age and vintage were time-updated in marginal structural models). All of the remaining covariates were recorded at baseline; parentheses are used to indicate the frequency with which they were assessed during follow-up. Comorbid diseases of interest included diabetes, arterial disease (ischemic heart disease, cerebral vascular disease, and/or peripheral vascular disease), and congestive heart failure (annually). Dialysis-related covariates included access type (quarterly), equilibrated Kt/V (every 6 weeks), and activated vitamin D use (biannually). Equilibrated Kt/V was calculated using the Daugirdas formula using blood urea nitrogen concentrations before and 20 minutes after dialysis (37). Laboratory covariates of interest included serum albumin, creatinine, phosphate, corrected calcium (38), and parathyroid hormone (biannually).

Anthropometric data included estimated dry weight (every 6 weeks), midarm muscle circumference, and triceps skin-fold thickness (annually). Midarm muscle circumference was calculated as arm circumference − (π*(triceps skinfold thickness)) (both in cm) (39). Other nutritional covariates considered were normalized protein catabolic rate (every 6 weeks), appetite assessment (annually), and use of enteral nutritional supplements (annually); parenteral supplement use was too infrequent to enable meaningful analysis. The normalized protein catabolic rate was calculated as 0.0136*([Kt/V]*[(predialysisBUN − 20 minutes postdialysisBUN)/2] + 0.251 (40).

Measured caloric and protein intake corrected for body weight were also considered as potential covariates (annually). These were assessed by a certified HEMO Study dietitian via two-day (one dialysis and one nondialysis, in most instances on consecutive days) dietary recall. All food, drink, and oral/enteral supplements were included in the dietary recall. The Nutritionist IV (version 3.5) program was used to convert the dietary recall diaries into dietary intake data.

Statistical Analyses

The subjects were considered at-risk beginning on day 90 after randomization (to enable capture of baseline dietary data that was not complete at the time of randomization) and remained at risk until death, transplant, or the end of the study. Baseline variables were considered as the latest observed value preceding the start of at-risk time. In longitudinal and time-updated analyses, time-varying variables were updated to reflect the most proximate value observed before the anniversary of the start of at-risk time.

Continuous and categorical variables were compared across categories of PDP by the Kruskal Wallis and χ2 tests, respectively. Longitudinal changes in continuous variables were examined by mixed effects linear regression; models contained the main-effects terms for PDP group and time, as well as PDP-by-time interaction terms (which represent the difference in slope over time according to PDP category); these models included a random-effects intercept term for patients to allow for inherent subject-specific differences and to minimize the effects of censoring on observed longitudinal trends. Changes in variables in the year after an alteration in PDP were compared between patients changed to more and less restrictive PDP by the paired t test.

The association between baseline PDP and subsequent survival was examined by Kaplan Meier methods and by unadjusted proportional hazards regression. Because of the number of potential confounders, multivariable adjustment was made by inverse probability of treatment weighting the proportional hazards model rather than by the introduction of individual covariate terms (41). Weights were estimated by a multinomial logistic regression model in which probability of observed PDP was the response variable, and covariates of interest were the predictor variables. Survival models were stratified on clinical center to minimize any potential center effect; the proportionality assumption was tested graphically and by examination of Schoenfeld residuals.

Marginal structural analysis was conducted through estimation of a pooled logistic regression model (42,43). In these analyses, follow-up time was divided into yearly intervals (to coincide with assessment of dietary intake variables); nonstatic covariates were time-updated. Multivariable adjustment for all covariates of interest in the original multivariable model was made by application of stabilized probability of exposure-times–stabilized probability of censoring weights as described previously (43–46). Sensitivity analyses were conducted among a priori specified subgroups to investigate for potential effect modification of the PDP mortality association on the basis of sex, race, baseline serum phosphate, and baseline activated vitamin D use.

For all survival analyses, we examined for and excluded potential effect modification on the basis of membrane type (high/low flux) and dose assignment (high/standard) through inclusion of two-way PDP-by-treatment group cross product terms. In addition, we introduced treatment group assignment indicator variables into all multivariable models and observed no appreciable effect on estimates (data not shown), indicating that there was no confounding on the basis of membrane type or dose assignment. All of the analyses were completed using STATA, versions 9.0 and 10.0MP (College Station, TX).

Results

Of the 1846 participants randomized in the HEMO study, 1751 had sufficient data for inclusion in the study cohort. At baseline, the mean age was 57.7 ± 14.0 years, 56.5% were female, 63.0% were black, 44.7% were diabetic, mean serum albumin was 3.6 ± 0.4 mg/dl, mean serum phosphate level was 5.8 ± 1.9 mg/dl, mean corrected serum calcium was 9.6 ± 1.0 mg/dl, 54.2% were using activated vitamin D, and 22.2% were using nutritional supplements.

The distribution of PDP at baseline is shown in Figure 1. On the basis of the staccato pattern observed, PDP was characterized by observed quartile with another category used to represent subjects with no prescribed restriction in dietary phosphate.

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Distribution of PDP among the study cohort. On the basis of the empiric distribution, PDP was categorized according to observed quartile (indicated by dashed lines), with a separate category used to represent subjects with no prescribed restriction of dietary phosphate.

Predictors and Metabolic Consequences of PDP

Baseline cross-sectional comparison of participant characteristics across categories of PDP is shown in Table 1. In general, participants with more restrictive PDP were more likely to be female, black, and dialyze via a graft. These participants tended to have evidence of poorer nutritional status (lower serum albumin, creatinine, body weight, midarm muscle circumference, and triceps skin-fold thickness; poorer appetite; and greater use of nutritional supplements) despite having greater caloric and protein intake. (To further explore whether differences in consumed calories and protein derived from differences in aggregate macronutrient intake or from lower body weight in more restrictive PDP groups, we alternatively examined protein and caloric intake as indexed to height: there were no significant differences in height-indexed protein intake [g/cm/d] across PDP groups [quartile (Q) 1, 0.38 ± 0.13; Q2, 0.37 ± 0.14; Q3, 0.39 ± 0.14; Q4, 0.40 ± 0.15; no prescription, 0.37 ± 0.13; global P value = 0.06]; height-indexed caloric intake [kcal/cm/d] was significantly different in at least one PDP group [global P value = 0.001], but there was no obvious trend with respect to the severity of prescribed dietary phosphate restriction [Q1, 9.4 ± 3.2; Q2, 9.0 ± 3.3; Q3, 9.1 ± 3.1; Q4, 9.9 ± 3.3; no prescription, 9.0 ± 3.0].)

View this table:
  • View inline
  • View popup
Table 1.

Baseline comparison of demographic, anthropometric, comorbidity, biochemical, and nutritional characteristics across categories of prescribed dietary phosphate

There was no consistent trend in serum phosphate or corrected calcium levels across PDP categories, but more restrictive PDP tended to cosegregate with high parathyroid hormone levels. Observed phosphate intake tended to track with PDP (except for the group with no specified phosphate prescription), but differences across groups were modest.

Mixed-effect linear models were used to examine postbaseline longitudinal trends in indices of nutritional status and metabolic bone disease control on the basis of baseline PDP. Serum phosphate tended to remain stable over time, and there was no consistent trend in longitudinal changes in serum phosphate across baseline PDP groups: serum phosphate tended to rise more among patients with baseline PDP 1000 and 1001 to 2000, but these differences in slope did not achieve statistical significance, and this trend did not extend to patients with the most permissive PDP (Figure 2A). Parathyroid hormone levels tended to rise overall, more so among patients with more liberal PDP (Figure 2B). There were no consistent trends across PDP groups in longitudinal change in corrected serum calcium, serum albumin, creatinine, normalized protein catabolic rate, body weight, midarm muscle circumference, triceps skin-fold thickness, or intake of calories, protein, or phosphate (data not shown). On time-updated cross-sectional analysis, more restrictive PDP was associated with a greater use of enteral nutritional supplements at all times between years 0 and 3 (Figure 3); data were too scant to provide for meaningful inference at later time points.

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Longitudinal changes in metabolic bone disease indices according to baseline PDP. (A) Overall, serum phosphate did not change over time (P = 0.77); although serum phosphate tended to rise more in quartiles 3 (PDP 1000 mg/d) and 4 (PDP 1001 to 2000 mg/d), these differences were not statistically significant from the referent group (PDP ≤870 mg/d): P for group-by-time interaction 0.12 and 0.38, respectively. (B) Overall, serum parathyroid hormone (PTH) tended to rise over time (P = 0.03), and this slope was greater among participants with more permissive PDP: P for group by time interaction 0.01, 0.05, and 0.11 for PDP 1000, 1001 to 2000, and no-restriction groups, respectively (referent PDP ≤870 mg/d). [Because of its highly skewed distribution, PTH was analyzed on the log scale and back transformed for this figure, accounting for the curvilinear appearance.]

Figure 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 3.

Use of dietary supplements over time among the categories of PDP. In these analyses, PDP was time updated to reflect the current year's prescription. P trend across PDP groups <0.001 within each year.

Baseline PDP was not necessarily instituted concurrently with study start but instead represented the level of the subjects' prevalent dietary phosphate prescription. Therefore, nutritional and metabolic bone parameters may have already achieved (or neared) steady-state before study start on the basis of prestanding PDP. To further explore the potential effect of PDP on these parameters, we examined their change over 1 year after a change in PDP (Table 2). Change to a more restrictive PDP tended toward greater reduction in serum phosphate, attenuated fall in corrected serum calcium, and more pronounced rise in triceps skin fold and body weight but also attenuated rise in caloric intake and greater reduction in midarm muscle circumference than change to a more permissive PDP; none of these trends achieved conventional levels of statistical significance. Of note, 17.1% of participants changed to more restrictive PDP versus 11.1% of those changes to more permissive PDP died in the year after the change (P difference was 0.02).

View this table:
  • View inline
  • View popup
Table 2.

Changes in indices of metabolic bone disease control, nutritional status, and body composition in the year after a change in prescribed dietary phosphate

Association between PDP and Survival

Overall, participants contributed a total of 4690 patient years of at-risk time during which 817 died; median follow-up time was 2.3 years. On unadjusted baseline analysis, PDP was not associated with mortality: compared with subjects with the most restrictive PDP, the hazard ratios (HRs) (95% confidence intervals [CIs]) for all-cause mortality were 0.91 (0.71 to 1.17), 0.90 (0.70 to 1.16), 0.92 (0.69 to 1.22), and 0.90 (0.68 to 1.18), for participants with PDP 871 to 999, 1000, 1001 to 2000 mg/d, and no restriction, respectively (Figure 4). Upon multivariable adjustment to correct for baseline differences between groups, the no-restriction group tended toward improved survival (HR (95% CI) 0.86 (0.61 to 1.22)), but this association did not achieve statistical significance. Results were largely unchanged upon further adjustment for protein and caloric intake.

Figure 4.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 4.

Association between PDP and all-cause mortality on baseline analyses. For each model, the referent group is PDP ≤870 mg/d. Multivariable models were adjusted, through application of inverse probability of treatment weights, for age, sex, race, dialysis vintage, access type, eKt/V, diabetes, congestive heart failure, arterial disease, serum albumin, serum creatinine, corrected serum calcium, serum phosphorus, serum parathyroid hormone, vitamin D use, estimated dry weight, triceps skin-fold thickness, midarm muscle circumference, normalized protein catabolic ratio, appetite assessment, and nutritional supplement use (each specified as per Table 1); two-way interaction terms with sex were included for estimated dry weight, triceps skin-fold thickness, and midarm muscle circumference to account for sex-specific differences in the prognostic significance of these variables. In addition, an expanded model (multivariable + intake) was fit that included all of the above covariates as well as observed caloric and protein intake (each normalized to body weight).

Overall, 29.1% of subjects had a change in PDP after baseline. To minimize exposure misclassification on this basis and to account for potential time-dependent confounding, we used marginal structural analysis to better estimate the association between PDP and survival. On marginal structural analysis, there was a stepwise trend toward greater survival with more liberal PDP (Figure 5A). Compared with the referent group with PDP ≤870 mg/d, the PDP 1001 to 2000 mg/d and no-restriction groups were associated with significant reductions in all-cause mortality: HRs (95% CIs) 0.73 (0.54 to 0.97) and 0.71 (0.55 to 0.92), respectively. Upon further adjustment for caloric and protein intake, the trend was quite similar. Although formal testing for interaction was not possible, the association between more permissive PDP and better survival seemed to be accentuated among nonblacks, participants with serum phosphate <5.5 mg/dl, and those who were not taking vitamin D on prespecified subgroup analyses (Figure 5B).

Figure 5.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 5.

Associations between PDP and survival using marginal structural models (MSM) to adjust for age, sex, race, dialysis vintage, access type, eKt/V, diabetes, congestive heart failure, arterial disease, serum albumin, serum creatinine, corrected serum calcium, serum phosphorus, serum parathyroid hormone, vitamin D use, estimated dry weight, triceps skin-fold thickness, midarm muscle circumference, normalized protein catabolic ratio, appetite assessment, nutritional supplement use, and two-way sex-interaction terms for estimated dry weight, triceps skin-fold thickness, and midarm muscle circumference using stabilized inverse probability of treatment and censoring weights. (A) Stratum-specific HRs (95% CIs) with and without additional inclusion of protein and caloric intake; the referent for each model is PDP ≤870 mg/d. (B) HRs (95% CIs) for no phosphate restriction (referent PDP ≤870 mg/d) among predefined subgroups (serum phosphate and vitamin D use categories are based on baseline values); stabilized weights were re-estimated within each group.

Discussion

Although phosphate restriction is a recommended first-line therapy for hyperphosphatemia, there has been no prior study of its long-term effects on mortality. Our primary finding was that prescribed dietary phosphate restriction was not associated with survival benefit and in fact may have been harmful.

One potential explanation for our findings is that prescribed phosphate restriction results in unintended reductions in intake of other beneficial macronutrients (29). Consistent with this hypothesis, more restrictive PDP cosegregated with poorer nutritional indices on baseline analysis. We were unable to demonstrate consistent trends in longitudinal changes in nutritional parameters on the basis of baseline PDP overall, perhaps because of participants having already achieved steady-state or because of informative censoring (e.g. selective death of subjects with worsening nutritional indices, which would attenuate observable difference among groups). However, changes to more restrictive PDP tended toward association with greater reductions in serum albumin, less robust rise in caloric intake, and replacement of lean body mass (midarm muscle circumference) with fat (triceps skin-fold) than changes to more permissive PDP.

The choice to consider prescribed phosphate restriction (as opposed to measured phosphate intake) as the exposure was premeditated and deliberate; our rationale was three-fold. First, dietary prescription is the point of potential intervention in clinical practice, and its consideration is consistent with intention-to-treat principles. Second, prescribed phosphate intake is less subject to confounding on the basis of comorbid conditions (i.e. those that predispose to both cachexia and death) than is measured phosphate intake. Finally, there have been no other studies that have specifically examined dietary phosphate prescription's association with mortality among HD patients. In fact, we are unaware of any study that has examined the association between any component of dietary prescription and survival among HD patients. Whether the prognostic significance of differences in spontaneous dietary intake across individuals is a valid surrogate for the efficacy of within-patient manipulations of dietary prescription remains uncertain given the potential for residual confounding and issues of patient adherence.

Our findings challenge the long-held belief that prescribed dietary phosphate restriction is beneficial (38,47,48). Recently, Kidney Disease Improving Global Outcomes released guidelines regarding the management of hyperphosphatemia in patients with chronic kidney disease, which includes a recommendation for prescribing dietary phosphate restriction alone or in combination with oral phosphate binders (19). Dietary phosphate restriction was considered a 2d recommendation, which is to say “weak,” with “very low” quality of evidence. The guidelines acknowledged the paucity of data to support this accepted practice and highlight the need for further studies. Our results suggest that there is little reason to favor the prescribed withholding of phosphate among hemodialysis patients, particularly in light of recent data suggesting that phosphate binders may improve survival in this population (49).

It bears great emphasis that these data pertain only to dietary phosphate restriction as is currently practiced. Although we are unaware of data regarding the precise nutritional advice given to patients regarding phosphate intake, our clinical experience dictates that most instruction centers on reducing intake of foods with intrinsically high phosphate levels; these foods (e.g. dairy, meats, legumes) tend to be nutrient dense. However, there has been growing awareness of the heavy use (and high bioavailability) of inorganic phosphates added to processed foods as preservatives. Given that these foods are not necessarily as nutritionally dense as those with naturally high phosphate content, it stands to reason that curtailment of processed food intake might result in less nutritional impairment and more favorable effects on survival. Dedicated study is warranted.

As with all observational studies, our results may be impacted by residual confounding. Although we attempted to adjust estimates for many factors that are associated with both PDP and survival, we acknowledge the possibility that other confounders exist. Most notably, we lacked data on (and therefore could not adjust for) phosphate binder use, which has recently been associated with improved survival in one observational study (49). However, national registry data from this era suggest that the vast majority of HD patients (80 to 88%) were receiving phosphate binders (50), which mitigates to some degree the likelihood that differences in use existed among PDP groups. Finally, considering that these data were obtained in the context of a clinical trial, it is likely that our participants were healthier than the general hemodialysis population. As such, further work is needed to examine the generalizability of our findings particularly to octagenarians, the obese, and patients with end-stage cardiac, hepatic, and pulmonary disease.

Conclusion

In conclusion, these data suggest that prescribed dietary phosphate restriction, as currently practiced, was not associated with improved survival among prevalent hemodialysis patients and may be associated with greater mortality, particularly in some patient subgroups. Further work is needed to confirm and generalize findings.

Disclosures

Dr. Brunelli's spouse is an employee at Genzyme. He serves on medical advisory boards to C.B. Fleet Co. and Amgen.

Acknowledgments

The Hemodialysis Study was conducted by the Hemodialysis Study Investigators and supported by the NIDDK. This manuscript was not prepared in collaboration with Investigators of the Hemodialysis Study and does not necessarily reflect the opinions or views of the Hemodialysis Study or the NIDDK. This work was presented in abstract form at the American Society of Nephrology Annual Meeting (November 16 through 21, 2010; Denver, Colorado) and was supported by NIH/NIDDK grant DK079056 (to S.M.B.).

Footnotes

  • Published online ahead of print. Publication date available at www.cjasn.org.

  • Received May 27, 2010.
  • Accepted October 21, 2010.
  • Copyright © 2011 by the American Society of Nephrology

References

  1. ↵
    1. Tentori F,
    2. Blayney MJ,
    3. Albert JM,
    4. Gillespie BW,
    5. Kerr PG,
    6. Bommer J,
    7. Young EW,
    8. Akizawa T,
    9. Akiba T,
    10. Pisoni RL,
    11. Robinson BM,
    12. Port FK
    : Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: The dialysis outcomes and practice patterns study (DOPPS). Am J Kidney Dis 52: 519–530, 2008
    OpenUrlCrossRefPubMed
  2. ↵
    1. Kimata N,
    2. Albert JM,
    3. Akiba T,
    4. Yamazaki S,
    5. Kawaguchi T,
    6. Fukuhara S,
    7. Akizawa T,
    8. Saito A,
    9. Asano Y,
    10. Kurokawa K,
    11. Pisoni RL,
    12. Port FK
    : Association of mineral metabolism factors with all-cause and cardiovascular mortality in hemodialysis patients: The Japan dialysis outcomes and practice patterns study. Hemodial Int 11: 340–348, 2007
    OpenUrlCrossRefPubMed
  3. ↵
    1. Young EW,
    2. Albert JM,
    3. Satayathum S,
    4. Goodkin DA,
    5. Pisoni RL,
    6. Akiba T,
    7. Akizawa T,
    8. Kurokawa K,
    9. Bommer J,
    10. Piera L,
    11. Port FK
    : Predictors and consequences of altered mineral metabolism: The dialysis outcomes and practice patterns study. Kidney Int 67: 1179–1187, 2005
    OpenUrlCrossRefPubMed
  4. ↵
    1. Slinin Y,
    2. Foley RN,
    3. Collins AJ
    : Calcium, phosphorus, parathyroid hormone, and cardiovascular disease in hemodialysis patients: The USRDS waves 1, 3, and 4 study. J Am Soc Nephrol 16: 1788–1793, 2005
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Port FK,
    2. Pisoni RL,
    3. Bommer J,
    4. Locatelli F,
    5. Jadoul M,
    6. Eknoyan G,
    7. Kurokawa K,
    8. Canaud BJ,
    9. Finley MP,
    10. Young EW
    : Improving outcomes for dialysis patients in the international dialysis outcomes and practice patterns study. Clin J Am Soc Nephrol 1: 246–255, 2006
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Pires A,
    2. Adragão T,
    3. Pais MJ,
    4. Vinhas J,
    5. Ferreira HG
    : Inferring disease mechanisms from epidemiological data in chronic kidney disease: Calcium and phosphorus metabolism. Nephron Clinical Practice 112: c137–c147, 2009
    OpenUrlCrossRefPubMed
  7. ↵
    1. Slatopolsky E,
    2. Brown A,
    3. Dusso A
    : Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis 37[Suppl 2]: S54–S57, 2001
    OpenUrlCrossRefPubMed
  8. ↵
    1. Imanishi Y,
    2. Inaba M,
    3. Nakatsuka K,
    4. Nagasue K,
    5. Okuno S,
    6. Yoshihara A,
    7. Miura M,
    8. Miyauchi A,
    9. Kobayashi K,
    10. Miki T,
    11. Shoji T,
    12. Ishimura E,
    13. Nishizawa Y
    : FGF-23 in patients with end-stage renal disease on hemodialysis. Kidney Int 65: 1943–1946, 2004
    OpenUrlCrossRefPubMed
  9. ↵
    1. Gupta A,
    2. Winer K,
    3. Econs MJ,
    4. Marx SJ,
    5. Collins MT
    : FGF-23 is elevated by chronic hyperphosphatemia. J Clin Endocrinol Metab 89: 4489–4492, 2004
    OpenUrlCrossRefPubMed
  10. ↵
    1. Lezaic V,
    2. Tirmenstajn-Jankovic B,
    3. Bukvic D,
    4. Vujisic B,
    5. Perovic M,
    6. Novakovic N,
    7. Dopsaj V,
    8. Maric I,
    9. Djukanovic L
    : Efficacy of hyperphosphatemia control in the progression of chronic renal failure and the prevalence of cardiovascular calcification. Clin Nephrol 71: 21–29, 2009
    OpenUrlPubMed
  11. ↵
    1. Cozzolino M,
    2. Brancaccio D,
    3. Gallieni M,
    4. Slatopolsky E
    : Pathogenesis of vascular calcification in chronic kidney disease. Kidney Int 68: 429–436, 2005
    OpenUrlCrossRefPubMed
  12. ↵
    1. Roman-Garcia P,
    2. Carrillo-Lopez N,
    3. Fernandez-Martin JL,
    4. Naves-Diaz M,
    5. Ruiz-Torres MP,
    6. Cannata-Andia JB
    : High phosphorus diet induces vascular calcification, a related decrease in bone mass and changes in the aortic gene expression. Bone 46: 121–128, 2010
    OpenUrlCrossRefPubMed
  13. ↵
    1. Gutierrez OM,
    2. Mannstadt M,
    3. Isakova T,
    4. Rauh-Hain JA,
    5. Tamez H,
    6. Shah A,
    7. Smith K,
    8. Lee H,
    9. Thadhani R,
    10. Juppner H,
    11. Wolf M
    : Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359: 584–592, 2008
    OpenUrlCrossRefPubMed
  14. ↵
    1. Block GA,
    2. Klassen PS,
    3. Lazarus JM,
    4. Ofsthun N,
    5. Lowrie EG,
    6. Chertow GM
    : Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 15: 2208–2218, 2004
    OpenUrlAbstract/FREE Full Text
  15. ↵
    1. Rennenberg RJ,
    2. Kessels AG,
    3. Schurgers LJ,
    4. van Engelshoven JM,
    5. de Leeuw PW,
    6. Kroon AA
    : Vascular calcifications as a marker of increased cardiovascular risk: A meta-analysis. Vasc Health Risk Manag 5: 185–197, 2009
    OpenUrlPubMed
  16. ↵
    1. Block GA,
    2. Hulbert-Shearon TE,
    3. Levin NW,
    4. Port FK
    : Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: A national study. Am J Kidney Dis 31: 607–617, 1998
    OpenUrlCrossRefPubMed
  17. ↵
    1. Noordzij M,
    2. Korevaar JC,
    3. Dekker FW,
    4. Boeschoten EW,
    5. Bos WJ,
    6. Krediet RT,
    7. Bossuyt PM,
    8. Geskus RB
    NECOSAD study group: Mineral metabolism and mortality in dialysis patients: A reassessment of the K/DOQI guideline. Blood Purif 26: 231–237, 2008
    OpenUrlCrossRefPubMed
  18. ↵
    1. Wald R,
    2. Sarnak MJ,
    3. Tighiouart H,
    4. Cheung AK,
    5. Levey AS,
    6. Eknoyan G,
    7. Miskulin DC
    : Disordered mineral metabolism in hemodialysis patients: An analysis of cumulative effects in the hemodialysis (HEMO) study. Am J Kidney Dis 52: 531–540, 2008
    OpenUrlCrossRefPubMed
  19. ↵
    Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group: KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl 113: S1–S130, 2009
    OpenUrlPubMed
  20. ↵
    1. Sullivan C,
    2. Sayre SS,
    3. Leon JB,
    4. Machekano R,
    5. Love TE,
    6. Porter D,
    7. Marbury M,
    8. Sehgal AR
    : Effect of food additives on hyperphosphatemia among patients with end-stage renal disease: A randomized controlled trial. JAMA 301: 629–635, 2009
    OpenUrlCrossRefPubMed
  21. ↵
    1. Ford JC,
    2. Pope JF,
    3. Hunt AE,
    4. Gerald B
    : The effect of diet education on the laboratory values and knowledge of hemodialysis patients with hyperphosphatemia. J Ren Nutr 14: 36–44, 2004
    OpenUrlCrossRefPubMed
  22. ↵
    1. Cupisti A,
    2. D'Alessandro C,
    3. Baldi R,
    4. Barsotti G
    : Dietary habits and counseling focused on phosphate intake in hemodialysis patients with hyperphosphatemia. J Ren Nutr 14: 220–225, 2004
    OpenUrlCrossRefPubMed
  23. ↵
    1. Combe C,
    2. Aparicio M
    : Phosphorus and protein restriction and parathyroid function in chronic renal failure. Kidney Int 46: 1381–1386, 1994
    OpenUrlPubMed
  24. ↵
    1. Williams PS,
    2. Stevens ME,
    3. Fass G,
    4. Irons L,
    5. Bone JM
    : Failure of dietary protein and phosphate restriction to retard the rate of progression of chronic renal failure: A prospective, randomized, controlled trial. Q J Med 81: 837–855, 1991
    OpenUrlPubMed
  25. ↵
    1. Sherman RA,
    2. Mehta O
    : Dietary phosphorus restriction in dialysis patients: Potential impact of processed meat, poultry, and fish products as protein sources. Am J Kidney Dis 54: 18–23, 2009
    OpenUrlCrossRefPubMed
  26. ↵
    1. Uribarri J
    : Phosphorus homeostasis in normal health and in chronic kidney disease patients with special emphasis on dietary phosphorus intake. Semin Dial 20: 295–301, 2007
    OpenUrlCrossRefPubMed
  27. ↵
    1. Ikizler TA
    : Dietary protein restriction in CKD: The debate continues. Am J Kidney Dis 53: 189–191, 2009
    OpenUrlCrossRefPubMed
  28. ↵
    1. Mehrotra R,
    2. Nolph KD
    : Low protein diets are not needed in chronic renal failure. Miner Electrolyte Metab 25: 311–316, 1999
    OpenUrlCrossRefPubMed
  29. ↵
    1. Rufino M,
    2. de Bonis E,
    3. Martin M,
    4. Rebollo S,
    5. Martin B,
    6. Miquel R,
    7. Cobo M,
    8. Hernandez D,
    9. Torres A,
    10. Lorenzo V
    : Is it possible to control hyperphosphataemia with diet, without inducing protein malnutrition? Nephrol Dial Transplant 13[Suppl 3]: 65–67, 1998
    OpenUrlCrossRefPubMed
  30. ↵
    1. Coladonato JA
    : Control of hyperphosphatemia among patients with ESRD. J Am Soc Nephrol 16[Suppl 2]: S107–S114, 2005
    OpenUrlAbstract/FREE Full Text
  31. ↵
    1. Kalantar-Zadeh K,
    2. Supasyndh O,
    3. Lehn RS,
    4. McAllister CJ,
    5. Kopple JD
    : Normalized protein nitrogen appearance is correlated with hospitalization and mortality in hemodialysis patients with Kt/V greater than 1.20. J Ren Nutr 13: 15–25, 2003
    OpenUrlCrossRefPubMed
  32. ↵
    1. Kalantar-Zadeh K,
    2. Kopple JD,
    3. Block G,
    4. Humphreys MH
    : A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients. Am J Kidney Dis 38: 1251–1263, 2001
    OpenUrlCrossRefPubMed
  33. ↵
    1. Lacson E Jr.,
    2. Ikizler TA,
    3. Lazarus JM,
    4. Teng M,
    5. Hakim RM
    : Potential impact of nutritional intervention on end-stage renal disease hospitalization, death, and treatment costs. J Ren Nutr 17: 363–371, 2007
    OpenUrlCrossRefPubMed
  34. ↵
    1. Pupim LB,
    2. Caglar K,
    3. Hakim RM,
    4. Shyr Y,
    5. Ikizler TA
    : Uremic malnutrition is a predictor of death independent of inflammatory status. Kidney Int 66: 2054–2060, 2004
    OpenUrlCrossRefPubMed
  35. ↵
    1. Eknoyan G,
    2. Beck GJ,
    3. Cheung AK,
    4. Daugirdas JT,
    5. Greene T,
    6. Kusek JW,
    7. Allon M,
    8. Bailey J,
    9. Delmez JA,
    10. Depner TA,
    11. Dwyer JT,
    12. Levey AS,
    13. Levin NW,
    14. Milford E,
    15. Ornt DB,
    16. Rocco MV,
    17. Schulman G,
    18. Schwab SJ,
    19. Teehan BP,
    20. Toto R
    Hemodialysis (HEMO) Study Group: Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 347: 2010–2019, 2002
    OpenUrlCrossRefPubMed
  36. ↵
    1. Greene T,
    2. Beck GJ,
    3. Gassman JJ,
    4. Gotch FA,
    5. Kusek JW,
    6. Levey AS,
    7. Levin NW,
    8. Schulman G,
    9. Eknoyan G
    : Design and statistical issues of the hemodialysis (HEMO) study. Control Clin Trials 21: 502–525, 2000
    OpenUrlCrossRefPubMed
  37. ↵
    1. Daugirdas JT
    : Estimation of equilibrated Kt/V using the unequilibrated post dialysis BUN. Semin Dial 8: 283–284, 1995
    OpenUrlCrossRef
  38. ↵
    National Kidney Foundation: K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42[Suppl 3]: S1–S201, 2003
    OpenUrlPubMed
  39. ↵
    1. Blumenkrantz MJ,
    2. Kopple JD,
    3. Gutman RA,
    4. Chan YK,
    5. Barbour GL,
    6. Roberts C,
    7. Shen FH,
    8. Gandhi VC,
    9. Tucker CT,
    10. Curtis FK,
    11. Coburn JW
    : Methods for assessing nutritional status of patients with renal failure. Am J Clin Nutr 33: 1567–1585, 1980
    OpenUrlAbstract/FREE Full Text
  40. ↵
    1. Lightfoot BO,
    2. Caruana RJ,
    3. Mulloy LL,
    4. Fincher ME
    : Simple formula for calculating normalized protein catabolic rate (NPCR) in hemodialysis (HD) patients (abstract). J Am Soc Nephrol 4: 363, 1993
    OpenUrl
  41. ↵
    1. Cole SR,
    2. Hernan MA
    : Adjusted survival curves with inverse probability weights. Comput Methods Programs Biomed 75: 45–49, 2004
    OpenUrlCrossRefPubMed
  42. ↵
    1. Robins JM,
    2. Hernan MA,
    3. Brumback B
    : Marginal structural models and causal inference in epidemiology. Epidemiology 11: 550–560, 2000
    OpenUrlCrossRefPubMed
  43. ↵
    1. Hernan MA,
    2. Brumback B,
    3. Robins JM
    : Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men. Epidemiology 11: 561–570, 2000
    OpenUrlCrossRefPubMed
  44. ↵
    1. Brunelli SM,
    2. Joffe MM,
    3. Israni RK,
    4. Yang W,
    5. Fishbane S,
    6. Berns JS,
    7. Feldman HI
    : History-adjusted marginal structural analysis of the association between hemoglobin variability and mortality among chronic hemodialysis patients. Clin J Am Soc Nephrol 3: 777–782, 2008
    OpenUrlAbstract/FREE Full Text
  45. ↵
    1. Brunelli SM,
    2. Chertow GM,
    3. Ankers ED,
    4. Lowrie EG,
    5. Thadhani R
    : Shorter dialysis times are associated with higher mortality among incident hemodialysis patients. Kidney Int 77: 630–636, 2010
    OpenUrlCrossRefPubMed
  46. ↵
    1. Teng M,
    2. Wolf M,
    3. Ofsthun MN,
    4. Lazarus JM,
    5. Hernan MA,
    6. Camargo CA Jr.,
    7. Thadhani R
    : Activated injectable vitamin D and hemodialysis survival: A historical cohort study. J Am Soc Nephrol 16: 1115–1125, 2005
    OpenUrlAbstract/FREE Full Text
  47. ↵
    1. Sherman RA
    : Dietary phosphate restriction and protein intake in dialysis patients: A misdirected focus. Semin Dial 20: 16–18, 2007
    OpenUrlCrossRefPubMed
  48. ↵
    1. Cupisti A,
    2. Morelli E,
    3. D'Alessandro C,
    4. Lupetti S,
    5. Barsotti G
    : Phosphate control in chronic uremia: Don't forget diet. J Nephrol 16: 29–33, 2003
    OpenUrlPubMed
  49. ↵
    1. Isakova T,
    2. Gutierrez OM,
    3. Chang Y,
    4. Shah A,
    5. Tamez H,
    6. Smith K,
    7. Thadhani R,
    8. Wolf M
    : Phosphorus binders and survival on hemodialysis. J Am Soc Nephrol 20: 388–396, 2009
    OpenUrlAbstract/FREE Full Text
  50. ↵
    1. Manley HJ,
    2. Garvin CG,
    3. Drayer DK,
    4. Reid GM,
    5. Bender WL,
    6. Neufeld TK,
    7. Hebbar S,
    8. Muther RS
    : Medication prescribing patterns in ambulatory haemodialysis patients: Comparisons of USRDS to a large not-for-profit dialysis provider. Nephrol Dial Transplant 19: 1842–1848, 2004
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

Clinical Journal of the American Society of Nephrology: 6 (3)
Clinical Journal of the American Society of Nephrology
Vol. 6, Issue 3
1 Mar 2011
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in CJASN.
Enter multiple addresses on separate lines or separate them with commas.
Prescribed Dietary Phosphate Restriction and Survival among Hemodialysis Patients
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Prescribed Dietary Phosphate Restriction and Survival among Hemodialysis Patients
Katherine E. Lynch, Rebecca Lynch, Gary C. Curhan, Steven M. Brunelli
CJASN Mar 2011, 6 (3) 620-629; DOI: 10.2215/CJN.04620510

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Prescribed Dietary Phosphate Restriction and Survival among Hemodialysis Patients
Katherine E. Lynch, Rebecca Lynch, Gary C. Curhan, Steven M. Brunelli
CJASN Mar 2011, 6 (3) 620-629; DOI: 10.2215/CJN.04620510
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Summary
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Conclusion
    • Disclosures
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data Supps
  • Info & Metrics
  • View PDF

More in this TOC Section

Original Articles

  • Incidence and Risk Factors for Dialysis Reinitiation among Patients with a History of Dialysis Dependency
  • Survey of Salary and Job Satisfaction of Transplant Nephrologists in the United States
  • Implications of Accumulated Cold Time for US Kidney Transplantation Offer Acceptance
Show more Original Articles

Epidemiology and Outcomes

  • Urine Kidney Injury Biomarkers and Risks of Cardiovascular Disease Events and All-Cause Death: The CRIC Study
  • Temporal and Demographic Trends in Glomerular Disease Epidemiology in the Southeastern United States, 1986–2015
  • Association between Monocyte Count and Risk of Incident CKD and Progression to ESRD
Show more Epidemiology and Outcomes

Cited By...

  • Dietary Therapy for Managing Hyperphosphatemia
  • Plant-Based Diets in CKD
  • Lack of Awareness of Dietary Sources of Phosphorus Is a Clinical Concern
  • Initiation of Sevelamer and Mortality among Hemodialysis Patients Treated with Calcium-Based Phosphate Binders
  • 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
  • Gastrointestinal Inhibition of Sodium-Hydrogen Exchanger 3 Reduces Phosphorus Absorption and Protects against Vascular Calcification in CKD
  • Interaction of Time-Varying Albumin and Phosphorus on Mortality in Incident Dialysis Patients
  • Google Scholar

Similar Articles

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Trainee of the Year
  • Author Resources
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • CJASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About CJASN
  • CJASN Email Alerts
  • CJASN Key Impact Information
  • CJASN Podcasts
  • CJASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Subscribe to ASN Journals
  • Wolters Kluwer Partnership

© 2022 American Society of Nephrology

Print ISSN - 1555-9041 Online ISSN - 1555-905X

Powered by HighWire