Third Annual
Soyfoods Symposium
Proceedings

 

Soyfoods in Chronic Renal Disease

by Dr. Paolo Fanti, MD, University of Kentucky

Renal disease is an important cause of morbidity and mortality in industrial and post-industrial societies. Over the last two decades, a steady rise in the longevity of the U.S. population has resulted in a parallel increment of prevalence of chronic renal disease. In 1995, 275,000 U.S. citizens were on renal replacement therapy (dialysis or transplantation) at a cost to the nation of $13 billion per year and the projections are that by the year 2010 there will be 1.1 million U.S. citizens on RRT at a cost exceeding $50 billion per year.(1) Dietary manipulation is fundamental to the management of renal disease, including chronic and acute renal failure as well as renal illnesses not characterized by loss of kidney function, such as renal stone disease and hypertension. Indeed, from a nutritional perspective, healthy kidneys are necessary for (1) the elimination of excess nitrogen and acid that derive from protein break-down, and of other by-products of nutrient utilization, (2) the elimination of excess dietary water, minerals and micronutrients like vitamins and phytochemicals, (3) the elimination of potential dietary toxins and (4) the biochemical activation of hormone-precursor nutrients such as vitamin D.

Soy is gaining popularity as a food item for human consumption in the U.S., in part because of a shift in interest of the American public toward plant food and in part because of the hypothesized health effects of soybeans. Reportedly, there are 26 million soyfoods consumers in this country. Our understanding of the potential impact of the introduction of soyfoods in the diet of patients with renal disease is in its infancy. However, integrated analysis of the current knowledge about the nutritional properties of soy, the metabolic derangement and dietary requirements of patients with kidney disease, and the handful of studies that have specifically addressed the issue of soyfoods utilization in renal disease, allow one to speculate in optimistic terms about the potential beneficial effects of soyfoods in renal patients.

Progression of renal disease and dietary protein. Patients with chronic renal disease progressing toward renal replacement therapy cope poorly with excessive protein intake, especially if this consists of animal proteins in the form of meat, eggs and dairy products. Indeed, degradation of excess dietary protein that is not supported by adequate elimination, like in chronic renal failure, leads to the accumulation of nitrogenous waste products, phosphorus and sodium. Not only are these the cause of many of the symptoms of renal failure, but their continued handling in large amounts by the failing kidney is believed to accelerate the progressive loss of renal function. For these reasons, protein restricted diets are of fundamental importance in the management of patients with chronic renal disease and have been utilized for more than three decades.(2,3) Unfortunately, the low protein diets are unpalatable. Their use is marred by problems of compliance(4) and their ability to prevent the uremic symptoms is less than complete. Soy protein: Studies in healthy subjects(5) have shown that soybean protein-based diets are associated with lower hydraulic pressure and lower workload for the filtering structures of the kidney, and with decreased urinary spillage of valuable blood constituents such as albumin. This beneficial effect of dietary soy seems to depend on its relatively low content of certain amino acids that are normally metabolized by the kidney and on its lack of inductive effect on blood flow and pressure in the kidneys, which is instead observed after an animal protein meal. Studies in rats with moderate renal insufficiency(6) showed that soy-based diets result in significantly longer survival, and lower renal damage, compensatory hypertrophy and proteinuria, than animal protein-based diets. Unfortunately, no conclusive evidence is available in patients with established renal insufficiency to demonstrate the superiority of soy protein over animal protein in slowing down the progression of renal disease. Recenly, Soroka, et al,(7) have compared prospectively the effects of animal and soy protein diets in patients with moderate to advanced renal failure. The diets were equally effective in preventing loss of renal function, although the soy diet was healthier because of its lower content of phosphorus and methionine, the precursor of homocystein. Although the study was well conducted and overall highly informative, it is questionable if the length of the trial was sufficient to demonstrate the superiority of either diet in protecting from progressive loss of renal function. Indeed, the trial was stopped after six months, while other studies on similar patient populations required longer dietary intervention to demonstrate an effect of nutrition on the progression of renal disease.(8) The lack of conclusive data may also be attributed to the fact that no information was reported about the rate of progression of renal disease prior to dietary intervention, and to the very low protein content of the experimental diets (0.7 g/kg/day), an amount that is known to prevent the progression of renal failure independently of the protein quality.

Proteinuria and dietary proteins. Proteinuria is the spillage of proteins and other important blood constituents in the urine and it is present in a good number of patients with chronic renal disease. Presence of proteinuria, especially if higher than 3 grams per day, is an ominous prognostic indicator since it opens the gate to a long list of medical complications and it hastens the progression toward end stage renal disease. Reduced dietary protein intake was shown to ameliorate the proteinuria and thus to reduce the chance for complications and to slow down the progression of kidney failure. Soy protein: Some evidence suggests that a low-protein diet including a large proportion of soy may be more effective than the conventional animal protein diets in reducing proteinuria. Patients with approximately two-thirds of normal kidney function and severe proteinuria (more than 6 grams per day) had 36% reduction in proteinuria following 4 months of soy protein diet(9) and the trend suggested that further improvement would have occurred if the dietary intervention had been continued. These authors speculated that the beneficial effect of soy is due, at least in part, to its lipid-lowering effect which is not shared by animal proteins. A study in diabetic patients with only modestly compromised renal function and microalbuminuria (a marker of renal suffering consequent to diabetes mellitus) showed that a 2-month intervention with a vegetarian diet reduced by 54% the albumin excretion.(10)

Blood vessel disease and dietary proteins. Patients with chronic renal failure have a very high, well-defined risk of premature blood levels disease,(11) which is responsible for approximately half of the deaths of the U.S. population on renal replacement therapy. Both case-control and prospective studies have shown that high blood levels of homocysteine (a by-product of the amino acid methionine) increase the risk of blood vessel disease in renal failure patients, independent of the other known risk factors such as diabetes, hypertension, lipid abnormalities and smoking. The homocysteine blood levels increase in proportion to the dietary intake of methionine and in patients with chronic renal disease the homocysteine levels increase more for a given methionine load than they do in normal individuals.(12) This poses a challenge for nutritionists who care for patients with renal insufficiency, since animal proteins are high in methionine and the renal protein-restricted diets, which usually contain animal proteins, provide a relatively large amount of methionine. Soy protein: The methionine content of a soy-based diet is much less than that of an animal protein-based diet,(5) and it was shown that the methionine blood levels are lower in experimental animals fed soy instead of animal-proteins.(13)

Renal bone disease and dietary proteins. Profound perturbations of the calcium phosphorus balance and development of metabolic bone disease are inevitable in patients with chronic renal disease.(14) The phosphorus and the acid loads associated with animal protein diets contribute to the problem. Dietary phosphorus represents a major challenge for patients with chronic renal disease. In fact, as the renal function worsens, the ability of the kidneys to excrete phosphorus is progressively lost. Thus, dietary intake of phosphorus inevitably leads to high blood levels of this element and to an imbalance of the calcium-phosphorus equilibrium. Over time, these changes can cause a number of medical problems, such as, the deposition of calcium-phosphorus salts in the soft tissues leading to their calcification; the development of hyperparathyroidism and of parathyroid tumors; and ultimately, bone disease. Besides retaining phosphorus, patients with chronic renal disease then accumulate hydrogen ions and develop acidosis (low pH of blood and other tissues). This has negative effects on several tissues and organs. The bone tissue and the hormones that regulate its metabolism are particularly sensitive to the acid build-up, so that calcium tends to be leached out of bone and parathyroid hormone tends to increase when the systemic pH is low.(15) Intake of animal protein is inevitably associated with high intake of phosphorus and acid. Soy protein: Conversely, the phosphorus and acid content of the soybean is relatively low. As a consequence, the phosphorus and acid intake of patients with renal insufficiency can be substantially reduced by switching from an animal-protein to a soy-protein diet.(7,9,10) Although no data was published to this effect, it is safe to assume that a soy-protein-based diet would be associated with less derangement of the calcium-phosphorus balance and of bone metabolism in patients with kidney failure.

References

(1) J Am Soc Nephrol 8(suppl 9):1-33, 1997.

(2) Giordano C. Use of exogenous and endogenous urea for protein synthesis in normal and uremic subjects. J lab Clin Med 62:231-246, 1963.

(3) Govanetti S, Maggiore Q. A low nitrogen diet with proteins of high biological value for severe chronic uremia. Lancet 1:1000-1003, 1964.

(4) Giovanetti S. The compliance with supplemented diet by chronic uremics and their nutritional status. Infusions Therapie 14(Suppl 5):4-7, 1987.

(5) Kontessis P, S Jones, R Dodds, R Trevisan, R Nosadini, P Fioretto, M Borsato, D Sacerdoti, GC Viberti. Renal, metabolic and hormonal responses to ingestion of animal and vegetable proteins. Kidney Int 38:136-144, 1990.

(6) Williams AJ, F Baker, J Walls. Effect of varying quantity and quality of dietary protein intake in experimental renal disease in rats. Nephron 46:83-90, 1987.

(7) Soroka N, DS Silverberg, M Greemland, Y Birk, M Blum, G Peer, A Iaina. Comparison of a vegetable-based (Soya) and an animal-based, low-protein diet in predialysis chronic renal failure patients. Nephron 79:173-180, 1998.

(8) Kopple JD, Levey AS, Greene T, Chumlea WC, Gassman J, Hollinger DL, Maroni BJ, Merrill D, Scherch LK, Shulman G, Wang S, Zimmer GS, for the Modification of Diet in Renal Disease Study Group. Effect of dietary protein restriction on nutritional status in the modification of diet in renal disease study. Kidney Int 52:778-791, 1997.

(9) Gentile MG, Fellin G, Cofano F, Delle Fave A, Manna G, Ciceri R, Petrini C, Lavarda F, Pozzi F, D'Amico G. Treatment of proteinuric patients with a vegetarian soy diet and fish oil. Clinical Nephrol 40:315-320, 1993.

(10) Jibani MM, Bloodworth LL, Foden E, Griffiths KD, Galpin OP. Predominantly vegetarian diet in patients with incipient and early clinical diabetic nephropathy: effects on albumin excretion rate and nutritional status. Diabet Med 8:949-953, 1991.

(11) Ibels LS, JH Stewart, JF Mahoney, FC Neale, AGR Sheil. Occlusive arterial disease in uremic and hemodialysis patients and renal transplant recipients. A study of the incidence of arterial disease and of the prevalence of risk factors implicated in the pathogenesis of arteriosclerosis. Q J Med 46:197-214, 1977.

(12) Hultberg B, A Anderson, G Sterner. Plasma homocysteine in renal failure. Clin Nephrol 40:230-234, 1993.

(13) Hagenmeister H, KE Scholz-Ahrens, H Schulte-Coerne, CA Barth. Plasma amino acid and cholesterol following consumption of dietary casein or soy protein in mini-pigs. J Nutr 120:1305-1311, 1990.

(14) Fani P, Sawaya BP. Renal osteodystrophy and aluminum intoxication. In: Current Therapy in Nephrology and Hypertension. Ed, R.J. Glassock. Mosby-Year Book, Inc., pp.265-301, 1998.

(15) Lefebvre A, de Vernejoul MC, Gueris J, Goldfarb B, Graulet AM, Morieux C. Optimal correction of acidosis changes progression of dialysis osteodystrophy. Kidney Int 36:11112-11118, 1989.

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