The Chronic Renal Insufficiency Cohort Study (CRIC) has recently shown potential benefits of vegetable protein intake in patients with mild-to-moderate CKD (J Ren Nutr 2012;22:379-388).

The observational, cross-sectional study includes 2,938 participants with an estimated glomerular filtration rate (eGFR) ranging from 20-70 mL/min/1.73m2 in eight clinical centers. A Diet History Questionnaire was administered to the participants at the first study visit to assess the percentage of animal versus plant protein consumed as well as other nutritional characteristics.

The median protein intake was 0.7g/kg body weight/day with an interquartile range of 0.5-1.0 g/kg/day. The median percentage of total protein obtained from plant sources was 33%, with an interquartile range of 26%-42%.


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The investigators stratified the percent plant protein intake into quintiles. With respect to demographics, age and female gender were positively associated with increased intake of vegetable protein, whereas body mass index (BMI) was negatively associated. Increased percentage of calories from carbohydrate sources increased with higher plant protein intakes, while fat and protein calories decreased.

Both total intakes and intakes adjusted for calorie consumption indicated lower intakes of sodium and phosphorus as plant protein increased, while potassium was only increased after adjusting for calorie intake. All three minerals showed decreased urinary concentrations with increasing plant protein consumption.

Effects on FGF-23

After applying an adjusted model, the study found that fibroblast growth factor 23 (FGF-23) was significantly negatively associated with percentage plant protein intake and serum bicarbonate was significantly positively associated.

This decrease in FGF-23 occurred even though serum phosphorus concentration did not significantly change related to vegetable protein intake. The reduced phosphorus intake and the fact that plant phosphorus compounds such as phytates are not easily absorbed in the human gut may account for the effects on FGF-23.

In addition, plant proteins contain reduced amounts of sulfur-containing amino acids. These amino acids markedly contribute to the acid load produced by protein. Thus, increased serum bicarbonate levels may be related to a decrease in sulfur amino acid load. These significant changes in FGF-23 and bicarbonate were seen in a population with a median vegetable protein intake of 33%. The changes may be more markedly pronounced in a population whose vegetable protein intake was increased more substantially.

FGF-23 is a hormone produced in the bone that down regulates phosphorus reabsorption in the kidney and also down regulates the conversion of 25-hydroxyvitamin D to the active form.

Thus, FGF-23 reduces serum phosphorus content by increasing excretion in the urine and decreasing absorption in the gut (Am J Kidney Dis 2012;59:135-144).

Oral ingestion of phosphorus supplements can directly increase FGF-23 levels in healthy populations within five days. FGF-23 expression is increased by both vitamin D and PTH, whereas FGF-23 itself down regulates the expression of both hormones, indicating a negative feedback loop.

Elevated plasma levels of FGF-23 have shown to be an independent risk factor for all-cause mortality in CKD and heart disease patients as well as a risk factor for progression to end-stage renal disease (ESRD) from CKD and to cardiovascular events in heart disease patients. These same results were not found in healthy populations.

In addition, FGF-23 has been shown to be associated with thickening of the heart and vascular tissues. FGF-23 is considered a novel marker for mortality risk and cardiovascular health, but it is unknown at this time whether FGF-23 itself is a pathophysiological agent.

In relation to the CRIC study, the mean eGFR was 44mL/min/1.73m2, and 67% of participants had CKD stage 3. Although serum phosphate levels were no different between groups even though intake was significantly different as % plant protein intake increased, FGF-23 decreased significantly, supporting the possibility that it is a more sensitive indicator of phosphorus balance in patients with mild-to-moderate CKD.

Contraindications

The results from the CRIC study demonstrate possible benefits from increased plant protein intake. Because of the benefits of protein restrictions, typical recommendations support a focus on high biological value protein sources, which primarily come from animal proteins.

Plant foods also have increased amounts of potassium, and elevated potassium levels can be detrimental in the presence of renal insufficiency. In addition, the lower calorie and lower biological value of proteins associated with vegetable diets may put patients at risk of protein-energy wasting as kidney function declines further.

Benefits of vegetable protein

Diets based on vegetable protein, however, may confer some advantages. Because vegetable sources are not often as concentrated in protein as animal sources, patients may find it easier to be compliant with protein restrictions during mild-to-moderate CKD.

Many meat products contain high amounts of sodium, saturated fat, and calories that can negatively impact blood pressure, blood lipids, and BMI. In the CRIC study, higher intakes of vegetable proteins were associated with reduced intakes of sodium, percent calories from fat, and BMI. In addition, higher plant protein intakes were associated with increased bicarbonate levels. These factors in combination with a restricted protein diet may help prolong kidney function and reduce the time until ESRD.

Furthermore, although potassium was significantly higher in relation to percentage of calories as plant protein intake increased, overall potassium intake was not significantly different between groups. In addition, urinary potassium excretion was lower with increased plant food intakes.

This effect may account for the increase in bicarbonate levels since potassium is often bound with alkaline inducing anions such as citrate. Reducing sulfur-containing amino acids while holding potassium and alkaline anion intake constant may have resulted in the increase in bicarbonate.

These potential benefits of vegetable proteins should be considered, and may be more appropriate in prolonging decline in renal function in patients with lower CKD stages who have less risk of protein-energy wasting and hyperkalemia.