Phosphate homeostasis, monitoring and managment of hyperphosphatemia in patients with the Chronic Kidney diseases

Higher serum phosphate concentrations are associated with mortality, and experimental data suggest that serum phosphate concentration is directly related to bone disease, vascular calcification and cardiovascular disease. Low-phosphorus diets and binders are used to help lower serum phosphate to reduce the long-term complications of CKD-MBD, although more research is needed to fully understand the disease-modifying impact of these interventions

There are actually 3 major sources of phosphates: natural phosphates (as cellular and protein constituents) contained in raw or unprocessed foods, phosphates added to foods during processing, and phosphates in dietary supplements/medications

In adults with CKD 3–5D, it is recommended to adjust dietary phosphorus intake to maintain serum phosphate levels within normal limits. In adults with CKD 1-5D or posttransplantation, it is reasonable when making decisions about phosphorus restriction treatment to consider the bioavailability of phosphorus sources (eg, animal, vegetable, additives). For adults with CKD posttransplantation with hypophosphatemia, it is reasonable to consider prescribing high-phosphorus intake (diet or supplements) in order to replete serum phosphate.

There are physiologic adaptations in the early stages of CKD that prevent excessive phosphorus retention, so the inability to increase phosphorus excretion to avoid phosphorus accumulation and hyperphosphatemia is generally seen when eGFR decreases to <45 mL/min,  being less common in earlier CKD stages. In the setting of anuria in patients receiving maintenance dialysis, hyperphosphatemia risks are particularly heightened, with a prevalence as high as 50%. CKD-specific recommendations suggest maintaining phosphorus intake between 800 and 1,000 mg/d in patients with CKD stages 3-5 and those receiving maintenance dialysis to maintain serum phosphate levels in the normal range

It is recommended to choose natural foods that are low in organic phosphorus over high in protein. The organic phosphorus content per gram of protein varies widely among different foods. Nutrient composition tables, which provide phosphorus to protein ratios, can be used to recommend meal replacement products that can significantly reduce daily organic phosphorus intake while ensuring adequate dietary protein intake

Below are tables with phosphorus content (g/mg) and phosphorus-to protein ratio (mg/g) in various foods and drinks

Table 1- Dietary P, protein, and potassium content of selected food items, ranked according to the P-to-protein ratio categories (Kalantar-Zadeh, Kamyar, 2010)

Substantial amounts of phosphoric acid are usually present in most colas and many other beverages.Many but not all clear-colored soft drinks or teas are low in P;however, most of these drinks contain little to no protein or other organic compounds, and the P is almost exclusively from additives. Being in liquid form, the inorganic P in these drinks are perhaps even more readily absorbable (Table 2). 

Table 2- P content of selected beverages, mostly as a result of additives (based on 12-oz serving) (Kalantar-Zadeh, Kamyar, 2010)

 

Table 3 illustrates variations in P content across diverse types of cheese in German-speaking regions of Europe. The quantity of P in a 50-g portion of cheese varies from <100 mg in Brie cheese to almost half a gram in processed soft cheese, which contains a significant amount of P salt.

 Table 3- Selected types of cheese consumed in German-speaking regions of Europe (Kalantar-Zadeh, Kamyar, 2010)

Table 4- Phosphorus/protein ratio per 100g of food (Barril-Cuadrado G, 2013)

In article provides tables of Phosphorus/protein ratio per 100g of uncooked food from organic animal and plant sources https://www.revistanefrologia.com/en-table-showing-dietary-phosphorus-protein-ratio-articulo-X2013251413003197

Table 5-  Phosphorus and Potassium Content of Commonly Consumed Beverages (Erica Wickham, 2014)

Table 6- Phosphorus Content of Foods According to Food Group (St-Jules DE, 2017) 

Food 
Serving Size 
Phosphorus (mg)
 
Per Serving        
Per 100 kcal    
 
Protein foods 
Chicken breast, roasted, skin removed        
3 oz 
194 
139 
Chicken breast, roasted 
3 oz 
182 
109 
Chicken breast, fried with batter 
3 oz 
157 
71 
Ground beef, 93% lean 
3 oz 
167 
103 
Ground beef, 70% lean 
3 oz 
141 
69 
Eggs 
2 large 
197 
138 
Black beans 
1 cup 
241 
106 
Peanut butter, creamy 
2 Tbsp 
107 
56 
Sesame seeds 
1 oz 
181 
113 
Dairy products 
Milk, skim 
1 cup 
247 
298 
Milk, whole 
1 cup 
205 
138 
Yogurt, low-fat, plain 
1 cup 
353 
229 
Yogurt, low-fat, vanilla 
1 cup 
331 
159 
Cheddar cheese 
1.5 oz 
193 
112 
Vanilla ice cream 
1 cup 
139 
51 
Grains 
Bread, white 
1 slice 
24 
36 
Bread, whole wheat 
1 slice 
68 
84 
Rice, brown 
1 cup 
208 
84 
Rice, white 
1 cup 
68 
33 
Cereal, Kellogg’s Corn Flakes 
1 cup 
29 
29 
Cereal, Kellogg’s All-Bran 
1 cup 
356 
445 
Bran muffin 
1 medium 
425 
139 
Croissant 
1 medium 
60 
26 
Fruits 
Apples 
1 cup 
12 
21 
Applesauce, sweetened 
1 cup 
18 
9 
Peaches 
1 cup 
31 
52 
Peaches, canned in juice 
1 cup 
42 
38 
Peaches, canned in heavy syrup 
1 cup 
29 
15 
Vegetables 
Carrots 
1 cup 
45 
87 
Broccoli 
1 cup 
60 
194 
Tomatoes 
1 cup 
43 
134 
Tomatoes, canned 
1 cup 
77 
100 
Tomatoes, canned, stewed 
1 cup 
51 
77 
Potatoes 
1 medium 
123 
73 
Potatoes, mashed 
1 cup 
101 
43 
Potatoes, French fries, McDonald’s 
1 medium 
149 
39

Table 7- PHOSPHORUS-TO-PROTEIN RATIO IN USUAL PORTIONS OF FOOD (Pereira, Raíssa & Ramos, 2020) 
Food
Amount (g)
Usual portion
Phosphorus (mg)
Protein (g)
Ratio phosphorus/protein (mg/g)
Meat and eggs
Chicken
80
1 medium breast fillet
150
23.0
6.5
Pork
80
1 medium pork chop
147
21.2
6.9
Beef
85
1 medium steak
209
26.0
8.0
Whitefish
84
1 medium fillet
241
20.6
11.7
Beef liver
85
1 medium steak
404
22.7
17.8
Sardine
34
1 unit
170
8.4
20.2
Whole egg
50
1 unit
90
6.0
15
Sausages
Sausage*
60
1 unit
126
13.9
9.1
Ham*
48
2 medium slices
136
14
9.7
Milk and dairy products
Cheese
30
2 thin slices
153
7.5
20.4
Requeijão *
30
1 tablespoon
134
2.9
46.2
Natural yogurt
120
1 small cup
159
6.3
25.2
UHT milk*
150
1 glass
140
4.9
28.6
Legumes and nuts
Cooked beans
154
1 medium ladle
133
6.9
19.3
Peanuts
50
1 small package
253
13
19.5

An analysis of phosphorus content (mg/100 g edible part) in the various food groups shows that the highest load comes from nuts, hard cheeses, egg yolk, meat, poultry and fish. Reporting the phosphorus content as mg per gram of protein (mg/g protein) is especially useful for identifying which foods supply less phosphorus with the same amount of protein. Based on the relationship between phosphorus and proteins, an upper limit of 12 mg/g is recommended to identify foods with “favorable” phosphorus to protein ratios (10,11).

For clarity of data, a number of countries have developed phosphorus pyramids (D'Alessandro C, 2015).

Figure - The phosphorus pyramid (D'Alessandro C, 2015)

Foods are distributed on six levels on the basis of their phosphorus content, phosphorus to protein ratio and phosphorus bioavailability. Each level has a colored edge (from green to red, through yellow and orange) that corresponds to recommended consumption frequency, which is the highest at the base (unrestricted intake) and the lowest at the top (avoid as much as possible). a) foods with unfavorable phosphorus to protein ratio (>12 mg/g); b) foods with favorable phosphorus to protein ratio (<12 mg/g); c) fruits and vegetables must be used with caution in dialysis patients to avoid excessive potassium load; d) Fats must be limited in overweight/obese patients, to avoid excessive energy intake; e) sugar must be avoided in diabetic or obese patients; f) protein-free products are dedicated to patients not on dialysis therapy and who need protein restriction but a high energy intake.
You can learn more about the phosphorus pyramid by following the link - https://bmcnephrol.biomedcentral.com/articles/10.1186/1471-2369-16-9.
 
Thus, in patients with CKD receiving dialysis, the daily phosphorus intake is up to 1000 mg. In the diet, it is recommended to take foods with sufficient levels of protein and reduced levels of phosphorus. It is recommended to keep PHOSPHORUS-TO-PROTEIN RATIO less than 12 mg/g.

Nutritional counseling sessions should evolve from the simple concept of phosphate restriction to оpportunities of educating the patient on differentiation between organic and inorganic sources of phosphate and avoidance of phosphate additives.

Bibliography:

  Phosphorus bioaccessibility

 Organic phosphorus: Organic phosphorus is bound to carbon-containing molecules. This type of phosphorus is present both in animal and plant-based foods but differ considerably in the form. In general, organic phosphorus from animal foods are about 40-60% bioavailable. In plants, phosphorus is mainly present in nuts, seeds, beans, legumes and grains, and fruits and vegetables contain only small amounts of phosphorus.  Unlike animal-based phosphorus, phosphorus in plants foods is mostlyfound in the form of phytic acid or phytate. Generally, plant-based phosphorus is thought to be less bioavailable than animal-based phosphorus (20-40% bioavailability).

Inorganic phosphorus: In contrast to organic phosphorus, inorganic phosphorus is found as free phosphate. Although inorganic phosphorus occurs naturally in food, the major source in the diet is from food additives that are used in a wide range of processed foods. Phosphorus additives serve a variety of useful functions in processed foods such as increasing shelf life, enhancing color and flavor, emulsifying, and acid-base buffering to name a few. Some common sources of phosphorus-containing food additives include dark colas, enhanced meats, frozen meals, cereals, snack bars, processed or spreadable cheeses, instant food products, and refrigerated bakery products. Generally, inorganic phosphorus has higher bioavailability (70%-100% bioavailability) as compared to organic phosphorus present in natural foods, though the exact bioavailability is controversial. Because phosphorus from food additives has higher bioavailability, the contribution of phosphorus from food additives is disproportionately higher than phosphorus naturally present in foods (Figure) (Dr. David St-Jules). 

     Cooking and processing methods can also influence both the amount and bioaccessibility of phosphorus in foods. For example, soaking has been shown to reduce the amount of phosphorus in foods including legumes, vegetables, cereals, and grains, as well as some animal-based foods (D.B. Vahia de Abreu et.al).  Wet-cooking methods and slicing meat have been shown to reduce phosphorus while maintaining protein content (S. Ando et.al.).
     However, in addition to the quantity of phosphorus present, processing techniques can also influence phosphorus bioaccessibility. In plants, especially cereals and grains, legumes, seeds, and nuts, phosphorus comes largely from phytate. Phytate is mostly indigestible due to the lack of phytase in the small intestine of humans and has limited accessibility due to its likelihood to chelate with other minerals. Processing techniques such as treatment with phytase, soaking, boiling (>140°C) for prolonged periods of time, fermenting, or germinating may increase the release of phosphorus from phytate and increase the proportion of phosphorus containing compounds less likely to chelate, potentially making the remaining phosphorus more bioaccessible for absorption (U. Schlemmer, E. Morris et.al).
      While culinary techniques including food processing are a potential tool to lower the phosphorus load from the diet, there are sparse data in this area, particularly as it relates to phosphorus bioavailability. Some culinary methods may both lower the overall quantity and increase the accessibility of phosphorus.

Table 9. Commonly used phosphorus additives used in the food industry, their purposes and food sources (Dr. David St-Jules) 

.

Table 10- Common phosphate additives used by food industry (Kalantar-Zadeh, 2010)

Most beverages contain little to no protein and, hence, any phosphate content is almost entirely from additives. As a consequence, patients who consume beverages with high phosphate content had serum phosphate levels that are often quite high whereas their nutritional status may be inferior. Additives can contribute more than 30% of the daily dietary phosphorus intake. 
Patients should review food labels to limit intake of foods high in phosphorus. For exemple: Pork Chops (Lean). Pork Fresh Loin Sirloin (Chops) Bone-In Separable Lean Only Cooked Braised, serving saze 170 mg - 6 oz - https://tools.myfooddata.com/nutrition-facts/167838/wt9.  170 grams of this product contains 515 mg of phosphorus. This product contains high levels of phosphorus. 85 mg (3 oz) of this product contains 257 mg of phosphorus, which corresponds to 21% of the recommended intake -https://tools.myfooddata.com/nutrition-facts/167838/wt1/1. 100 grams of this product contains 303 mg of phosphorus or 24% of the recommended intake - https://tools.myfooddata.com/nutrition-facts/167838/100g/1.200 kilocalories (103 g) of this product contain 311 mg of phosphorus - 25% of the recommended intake - https://tools.myfooddata.com/nutrition-facts/167838/200cals/1. 
Thus, knowing the level of phosphorus, a patient with CKD stage 5 can select foods with low levels of phosphorus.
Patient education is important: creating websites with information, brochures, manuals, infographics.

Examples are given below

• https://blogs.davita.com/kidney-diet-tips/high-phosphorus-get-facts/
  

• https://www.eatright.org/health/health-conditions/kidney-disease/kidney-disease-and-diet

• https://www.davita.com/diet-nutrition/kidney-friendly-cookbooks

• https://www.davita.com/diet-nutrition/articles

• https://aakp.org/center-for-patient-research-and-education/kidney-friendly-recipes/

•  https://lesdieteticiens.be/actu-dieta-18-septembre-2023/

•  https://www.eatright.org/health/health-conditions/kidney-disease/kidney-disease-and-diet

• https://ods.od.nih.gov/HealthInformation/nutrientrecommendations.aspx#dri

• https://www.isrnm.org/patientscorner
• https://ods.od.nih.gov/factsheets/Phosphorus-HealthProfessional/
  

Conclusion
Dietary intake of P is derived largely from foods with high protein content or food additives and is an important determinant of P balance in patients who have CKD and have a greatly reduced GFR. PO₄ additives can dramatically increase the amount of P consumed in the daily diet, especially because P is more readily absorbed in its inorganic form. In contrast, plant foods, including seeds and legumes that are high in P, are usually associated with the least intestinal P absorption because of the phytate in these foods. Hence, the P burden from food additives in fast foods, soft drinks, and processed cheese and snacks is disproportionately high relative to its dietary P content compared with natural P sources from animal and plant protein. In patients with CKD, a mixed composition of dietary animal and plant foods that are rich in phytic acid should be encouraged, whereas the intake of processed foods should be limited.  The increased use of P additives in food, coupled with the increased popularity of convenience foods and frequenting of fast food restaurants, has greatly increased the amount of P consumed by both the general population and patients with CKD. Meals that have lower amounts of organic and particularly inorganic P and are rich in high-value protein, along with P binders, can be provided during long hemodialysis treatment sessions to patients with CKD within inside dialysis clinics and monitored in-center by renal dietitians and nephrologists.  

Bibliography: