Is controlling phosphorus by decreasing dietary protein intake beneficial or harmful in persons with chronic kidney disease?

Abstract

Background: Dietary restrictions to control serum phosphorus, which are routinely recommended to persons with chronic kidney disease, are usually associated with a reduction in protein intake. This may lead to protein-energy wasting and poor survival.

Objective: We aimed to ascertain whether a decline in serum phosphorus and a concomitant decline in protein intake are associated with an increase in the risk of death.

Design: In a 3-y study (7/2001-6/2004) of 30 075 prevalent maintenance hemodialysis (MHD) patients, we examined changes in serum phosphorus and in normalized protein nitrogen appearance (nPNA), a surrogate of dietary protein intake, during the first 6 mo and the subsequent mortality. Four groups of MHD patients were defined on the basis of the direction of the changes in serum phosphorus and nPNA.

Results: Baseline phosphorus had a J-shaped association with mortality, whereas higher baseline nPNA was linearly associated with greater survival. Compared with MHD patients whose serum phosphorus and nPNA both rose over 6 mo, those whose serum phosphorus decreased but whose nPNA increased had greater survival, with a case mix-adjusted death risk ratio of 0.90 (95% confidence limits: 0.86, 0.95; P < 0.001), whereas those whose phosphorus increased but whose nPNA decreased or those whose phosphorus and nPNA both decreased had worse mortality with a risk ratio of 1.11 (1.05,1.17; P < 0.001) and 1.06 (1.01,1.12; P = 0.02), respectively.

Conclusions: The risk of controlling serum phosphorus by restricting dietary protein intake may outweigh the benefit of controlled phosphorus and may lead to greater mortality. Additional studies including randomized controlled trials should examine whether nondietary control of phosphorus or restriction of nonprotein sources of phosphorus is safer and more effective.

Conflict of interest statement

Potential Conflict of Interest:

KKZ, CPK, RM and JDK have received grants and/or honoraria from Amgen (manufacturer of Sensipar™), Abbott (manufacturer of Calcijex™ and Zemplar™), Genzyme (manufacturer of Hectoral™, Renagel™ and RenVela™), and/or Shire (manufacturer of Fosrenol™). Other authors have not declared conflicts of interest.

Figures

Figure 1

The association between the baseline dietary protein intake, represented by 13-week averaged nPNA (nPCR), and 13-week averaged serum phosphorus in 30,075 MHD patients in the baseline calendar quarter of the cohort. Error bars represent standard deviation. P for trend

Figure 2

Comparing the 3-year mortality predictabilities of the baseline dietary protein intake, represented by nPNA (nPCR), and serum phosphorus concentration, as well as their changes over time using Cox regression models in 30,075 MHD patients. The Y-axis shows the logarithm of the risk ratio of all-cause mortality over 3 years of observation, i.e., July 2001 to June 2004. The multivariable regression spline models are adjusted for case-mix and MICS. Dashed lines are 95% pointwise confidence levels. Upper Right Panel: Baseline, 13-week averaged nPNA. Upper Left Panel: Baseline, 13-week averaged serum phosphorus concentration. Lower Right Panel: Changes in the 13-week averaged nPNA over two consecutive calendar quarters. Lower Left Panel: Changes in the 13-week averaged serum phosphorus concentration over two consecutive calendar quarters.

Figure 3

Mortality predictability of the combinations of the percentiles of the changes in dietary protein intake, represented by nPNA (nPCR), and serum phosphorus (PO4) concentration in 30,075 MHD patients. The Y-axis shows the logarithm of the risk ratio of all-cause mortality over 3 years based on a multivariable Cox regression spline model, adjusted for case-mix and MICS. Dashed lines are 95% pointwise confidence levels. Each patient received a percentile score between 0.01 and 0.99 according to the percentile rank of the change in nPNA or serum phosphorus. The sum of the two percentile scores for each patient resulted in a number between 0.02 and 1.98 (Right Panel), whereas the difference between nPNA and serum phosphorus concentration in each patient resulted in a number between −0.98 and +0.98 (Left Panel).

Figure 4

The 3-year death risk ratios of the four combinations of the changes in serum phosphorus (PO4) concentration and dietary protein intake, measured via nPNA (nPCR), over two consecutive calendar quarters in 30,075 MHD patients using Cox regression model.

Figure 5

The 3-year death risk ratio of the baseline dietary protein intake (nPNA or nPCR) ≥1.0 g/kg/day (vs.