Inadequate Awareness among Chronic Kidney Disease Patients Regarding Food and Drinks Containing Artificially Added Phosphate

<div><p>Hyperphosphatemia is an important determinant of morbidity and mortality in patients with chronic kidney disease (CKD). Patients with CKD are advised to consume a low phosphate diet and are often prescribed phosphate-lowering drug therapy. However, commercially processed food and drinks often contain phosphate compounds, but the phosphate level is not usually provided in the ingredient list, which makes it difficult for CKD patients to choose a correct diet. We conducted a survey of the awareness of food/beverages containing artificially added phosphate among CKD patients undergoing hemodialysis. The subjects were 153 patients (77 males and 76 females; average age 56±11 years) who were randomly selected from the Dialysis Center of Hirosaki City, Japan. The subjects were provided with a list of questions. The survey results showed that 93% of the subjects were aware of the presence of high sugar content in soda, whereas only 25% were aware of the presence of phosphate (phosphoric acid) in such drinks. Despite 78% of the subjects being aware of the detrimental effects of consumption of a high phosphate diet, 43% drank at least 1 to 5 cans of soda per week and about 17% consumed “fast food” once each week. We also assessed the immediate effects of high-phosphate containing carbonated soda consumption by determining urinary calcium, phosphate, protein and sugar contents in overnight fasted healthy volunteers (n = 55; average age 20.7±0.3 years old, 20 males and 35 females). Significantly higher urinary calcium (adjusted using urinary creatinine) excretion was found 2 h after consuming 350 ml of carbonated soda compared to the fasting baseline level (0.15±0.01 vs. 0.09±0.01, p = 0.001). Our survey results suggest that CKD patients undergoing hemodialysis are not adequately aware of the hidden source of phosphate in their diet, and emphasize the need for educational initiatives to raise awareness of this issue among CKD patients.</p></div

The survey participant CKD patients were asked whether they were aware of the possible harmful effects of unrestricted consumption of a high phosphate diet, and the majority (78%) of the participants was aware of detrimental effects related to high phosphate diet.

<p>The survey participant CKD patients were asked whether they were aware of the possible harmful effects of unrestricted consumption of a high phosphate diet, and the majority (78%) of the participants was aware of detrimental effects related to high phosphate diet.</p

The survey participant CKD patients were asked whether they were aware of the sugar and phosphate content in commercially available soda drinks.

<p>Almost 93% of the participants were aware of the presence of sugar, while only 25% were aware of the presence of phosphate (phosphoric acid) in such drink, showing a noticeable awareness gap related to phosphate-contenting drinks among the patients.</p

The survey participant CKD patients were asked whether they were willing to modify their diet to reduce phosphate intake.

<p>Around 35% of the participants wanted to have more information related to artificially containing-food and drinks, and another 45% were willing to reduce their phosphate intake by minimizing consumption of processed food and soda drinks.</p

The participants were asked to describe their soda drink and fast food consumption habits.

<p>Almost half (51%) of the CKD patients drink soda, while 39% patients eat fast food.</p

Enhanced p122RhoGAP/DLC-1 Expression Can Be a Cause of Coronary Spasm

<div><p>Background</p><p>We previously showed that phospholipase C (PLC)-δ1 activity was enhanced by 3-fold in patients with coronary spastic angina (CSA). We also reported that p122Rho GTPase-activating protein/deleted in liver cancer-1 (p122RhoGAP/DLC-1) protein, which was discovered as a PLC-δ1 stimulator, was upregulated in CSA patients. We tested the hypothesis that p122RhoGAP/DLC-1 overexpression causes coronary spasm.</p><p>Methods and Results</p><p>We generated transgenic (TG) mice with vascular smooth muscle (VSM)-specific overexpression of p122RhoGAP/DLC-1. The gene and protein expressions of p122RhoGAP/DLC-1 were markedly increased in the aorta of homozygous TG mice. Stronger staining with anti-p122RhoGAP/DLC-1 in the coronary artery was found in TG than in WT mice. PLC activities in the plasma membrane fraction and the whole cell were enhanced by 1.43 and 2.38 times, respectively, in cultured aortic vascular smooth muscle cells from homozygous TG compared with those from WT mice. Immediately after ergometrine injection, ST-segment elevation was observed in 1 of 7 WT (14%), 6 of 7 heterozygous TG (84%), and 7 of 7 homozygous TG mice (100%) (p<0.05, WT versus TGs). In the isolated Langendorff hearts, coronary perfusion pressure was increased after ergometrine in TG, but not in WT mice, despite of the similar response to prostaglandin F_2α between TG and WT mice (n = 5). Focal narrowing of the coronary artery after ergometrine was documented only in TG mice.</p><p>Conclusions</p><p>VSM-specific overexpression of p122RhoGAP/DLC-1 enhanced coronary vasomotility after ergometrine injection in mice, which is relevant to human CSA.</p></div

Representative ECG recordings and responses to ergometrine in wild type (WT) and transgenic (TG) mice.

<p><b>(</b>A) Representative ECG recordings before (left) and after (right) intravenous injection of ergometrine in anesthetized homozygous TG mouse. Ergometrine injection immediately elicited ST-segment elevation with PR prolongation. (B) Incidence of ST-segment elevation after ergometrine injection in WT, heterozygous, and homozygous TG mice. (C) Representative ECG showing advanced AV block in homozygous TG mice after ergometrine injection.</p

PLC activity in cultured vascular smooth muscle cells.

<p>(A) PLC activity in the plasma membrane fraction (n = 3 in WT and TG mice). (B) PLC activity in the whole cell (n = 3 in WT and TG mice).</p

Generation of transgenic (TG) mice and their expression analyses.

<p>(A) Schematic map of the microinjected transgene consisting of the α-smooth muscle actin promoter and the mouse p122RhoGAP/DLC-1 cDNA. (B) Representative bands (131 bp) after genomic PCR and representative amplification curves for p122RhoGAP/DLC-1 and GAPDH in real-time PCR (40 cycles). (C) The gene expression of mouse p122RhoGAP/DLC-1 in various tissues of wild type (WT) (n = 3) and homozygous TG mice (n = 3). The ratio of p122RhoGAP/DLC-1 to GAPDH expression in the liver of WT mice was used as a reference (= 1), since it showed the lowest value among the tissues of WT mice. (D) Representative bands for mouse p122RhoGAP/DLC-1 protein in the pooled aortas (left panel) and densitometric analysis between WT and homozygous TG mice (right panel). The aortas from 4 mice in WT and TG.</p

Microvascular filling experiment with microfil of the coronary arteries in wild type (WT) and homozygous transgenic (TG) mice.

<p>In the group treated with vehicle, no focal narrowing was observed in either WT (n = 3) or TG mice (n = 3). Focal narrowing (arrows) of the coronary artery after injection of ergometrine was observed in homozygous TG (3 of 3), but not in WT mice (0 of 3).</p