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Hyperlipidemic factors contribute to the high cardiovascular risk in hemodialysis patients and may accelerate the progression of renal disease. Soy protein has been shown to reduce some atherogenic lipid concentrations in subjects with normal renal function, and slow progression of renal injury, reduce blood pressure in experimental animals and human subjects. The mechanism and components of soy responsible have not been fully established. The objectives of this study were to 1) evaluate the effect of soy protein on serum lipid profiles and lipoprotein metabolism in hyperlipidemic and normolipidemic hemodialysis patients. 2) investigate the effect of the two fractions of soy protein hydrolysate on renal function, blood pressure and lipid metabolism in five-sixths nephrectomized rats, and to examine the active components of soy protein hydrolysate on ameliorating disease progression. Hyperlipidemic and normolipidemic hemodialysis patients were enrolled in a randomized, double-blind, placebo-controlled clinical trial. Thirty grams of isolated soy protein or milk protein was consumed daily as a beverage at breakfast or postdialysis for 12 wk. Experimental animals were subjected to a nephrectomy and were fed two fractions isolated from soy protein hydrolysate prepared by peptic hydrolysis for 13 wk. Results showed soy protein substitution significantly reduced total cholesterol, triglyceride, low-density lipoprotein cholesterol and apolipoprotein B concentrations, and the HDL-cholesterol was significantly increased in hyperlipidemic subjects. There were no significant changes in serum lipid and lipoprotein concentrations in normolipidemic subjects. Both soy protein hydrolysate fractions favorably affected chronic renal failure. The supernatant fraction of soy protein hydrolysate had the most-significant decreases in blood pressure and significantly retarded progression of the experimentally induced renal disease. The precipitate fraction of soy protein hydrolysate exhibited significantly increased fecal excretion of total cholesterol. In conclusion, our findings demonstrate that replacing a part of the daily protein with soy protein could be used in the nutritional management of moderately hyperlipidemic hemodialysis patients. The supernatant fraction of soy protein hydrolysate had most-pronounced effect on slowing the progression of renal disease, and the precipitate fraction of soy protein hydrolysate had a protective effect on renal function resulting from lowering cholesterol.
Effect of soy protein on blood pressure, lipid metabolism and renal function in chronic renal failure
Angiotensin converting enzyme plays a key physiological role in the activation of RAS (rennin-angiotensin system). We investigated the effects of pepsin-digested soy protein hydrolysate (SPH) on blood pressure and ACE activity in three different animal models in this study. In 5/6-nephrectomized rats, we found soy protein and SPH had the same renoprotective effects and decrease systolic blood pressure, plasma insulin and renal TNF-a (tumor necrosis factor-a) concentration. In rats with metabolic syndrome induced by high-fructose-high-fat diet, SPH was also as effective as soy protein in the reduction of blood pressure, plasma glucose and lipids. The soy protein and SPH group also had lower plasma, heart and renal ACE activity and tissue TNF-a and PAI-1 (plasminogen activator inhibitor-1) level than the control group. However, no difference in plasma and adipose adiponectin level was found. In the third part of study, we fed NO-deficient hypertensive rats diet containing 1%, 3% or 5% SPH. We found that the 5% SPH group had lower blood pressure, heart and renal ACE activity, renal PAI-1, TNF-a level and CYP4A expression than the control group. In pathohistological analysis, we also found that 5% SPH can protective cardiovascular and renal injuries caused by administration of NO synthase inhibitor. Furthermore, we isolated the peptides with ACE inhibitory activities in SPH, and we found that LKNQRESY, DQMPRRF and LVPPQESQRR were the three most effective peptides derived from soy protein. Therefore, we suggested that one possible mechanism of the beneficial effects of soy protein consumption on hypertension and related tissue injuries may be the ACE inhibitory peptide derived from digested soy protein.