Diet Strategy for Hyperphosphatemic Patients in End-Stage Renal Disease

• Main Authors: Wan-Chuan Tsai, 蔡萬全
• Other Authors: Kuo-Liong Chien
• Format: Others
• Language: en_US
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/p588s3

博士 === 國立臺灣大學 === 流行病學與預防醫學研究所 === 107 === Background: Patients with end-stage renal disease (ESRD) are at an increased risk for developing cardiovascular disease, and premature death. Emerging evidence suggests that disordered mineral metabolism including hyperphosphatemia, fibroblast growth factor 23 (FGF23) excess, secondary hyperparathyroidism, and vitamin D deficiency contribute to the high rates of adverse outcomes. Dietary phosphate restriction is a preferred way to ameliorate altered mineral metabolism, but yields conflicting results on FGF23. For hemodialysis patients who have hyperphosphatemia, current guidelines recommend the metric phosphate-to-protein ratio (PPR) to select foods with a PPR value of 10 – 12 mg/g, fulfilling low phosphorus purpose while ensuring adequate protein intake. The accuracy of PPR in nutrient database and the optimal amount of dietary phosphate restriction are undefined. The objectives of this dissertation are (1) to examine the accuracy of nutrient database estimating PPR, (2) to assess diet-mediated FGF23-lowering effect using a systematic review and meta-analysis, and (3) to investigate the effect of low-phosphate diet on FGF23, and assess the optimal amount of dietary phosphate restriction in hemodialysis patients. Methods: (1) Accuracy of nutrient database regarding PPR in 20 cooked dishes selected from the hospital menu was determined. (2) Four database (Medline, PubMed, Embase, and Cochrane Library) were systematically searched for randomized clinical trials (RCTs) that examined FGF23-lowering effects of low-phosphate diets to conduct a random-effects meta-analysis. (3) In a randomized crossover trial, adults with ESRD and hyperphosphatemia were randomly assigned to receive a very-low-phosphate diet (PPR 8 mg/g, equivalent to phosphate content less than 600 mg/d), or a low-phosphate diet (PPR 10 mg/g, equivalent to phosphate content less than 800 mg/d) for two days. The primary outcome was mean difference in change-from-baseline intact FGF23 level between intervention groups. Secondary outcomes included changes in serum phosphate, intact parathyroid hormone (PTH), and C-terminal FGF23 level. Results: (1) There is a substantial variation in differences of nutrients (estimated values based on nutrient database – measured values) among study foods. Comparisons of estimated values with measured values for every 100 g of tested foods revealed a significant overestimation for the PPR (mean difference ± SD, 3.5 ± 12.2 mg/g, P = 0.008). (2) In the systematic review, five RCTs of patients with chronic kidney disease (CKD) were identified and no study enrolled dialysis patients. The meta-analysis revealed that lower phosphate diets tended to reduce FGF23 levels, compared with higher phosphate diets (standardized mean difference, -0.74; 95% CI, -1.54 to 0.07; P = 0.07). (3) A total of 35 patients consumed study diets and 29 completed the trial. Both low-phosphate diets significantly decreased intact FGF23, phosphate, and intact PTH levels relative to baseline values, but no change in C-terminal FGF23 level. Relative to the low-phosphate diet, the very-low-phosphate diet had no significant effect on the level of intact FGF23, intact PTH, or C-terminal FGF23 but lowered the serum phosphate level (mean difference, 0.6 mg/dL; 95% CI, 0.2 to 1.0; P = 0.002). Conclusions: Caution should be exercised in estimating the PPR using a nutrient database to prepare hospital diets. Dietary phosphate restriction may reduce FGF23 levels in CKD patients. For hemodialysis patients, the very-low-phosphate diet offered no additional benefit for FGF23 reduction but provided a greater phosphate-lowering effect.