Prescribed dietary phosphate restriction and survival among hemodialysis patients

Abstract

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.

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.

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.

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.

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).

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.