lignans and Kidney-Failure--Chronic

There is growing evidence that dietary phytoestrogens have a beneficial role in chronic renal disease. This review summarizes the recent findings from dietary intervention studies performed in animals and humans suggesting that consumption of soy-based protein rich in isoflavones and flaxseed rich in lignans retards the development and progression of chronic renal disease. In several animal models of renal disease, both soy protein and flaxseed have been shown to limit or reduce proteinuria and renal pathological lesions associated with progressive renal failure. In studies of human subjects with different types of chronic renal disease, soy protein and flaxseed also appear to moderate proteinuria and preserve renal function. However, most of these clinical trials were of relatively short duration and involved a small number of patients. Furthermore, it is not clear whether the renal protective effects of soy protein and flaxseed are caused by the isoflavones (daidzein and genistein) and lignans (matairesinol and secoisolariciresinol) or some other component. The biochemistry, metabolism, and mechanisms of actions of isoflavones and lignans are discussed. Isoflavones and lignans appear to act through various mechanisms that modulate cell growth and proliferation, extracellular matrix synthesis, inflammation, and oxidative stress. Some of these actions have been shown in vitro, but studies of the mechanisms operative in vivo are lacking. The diversity of cellular actions of isoflavones and lignans supports their protective effects in a variety of experimental and human types of chronic renal disease. Further investigations are needed to evaluate their long-term effects on renal disease progression in patients with chronic renal failure.

Topics: Animals; Caseins; Disease Progression; Estrogens, Non-Steroidal; Female; Flax; Humans; Isoflavones; Kidney Failure, Chronic; Lignans; Mice; Phytoestrogens; Plant Preparations; Rats; Rats, Inbred F344; Soybean Proteins

Phytoestrogens are naturally occuring plant compounds that are present primarily in soybeans as isoflavones and in flaxseed as lignans. Because of their structural similarity to endogenous estrogens, phytoestrogens bind to both estrogen receptors (ER)-alpha and beta (but more strongly to ER-beta) and exert estrogen-like effects. There is increasing evidence that dietary phytoestrogens have a beneficial role in chronic renal disease. Nutritional intervention studies have shown that consumption of soy-based protein and flaxseed reduces proteinuria and attenuates renal functional or structural damage in animals and humans with various forms of chronic renal disease. It is not clear which component(s) of the soybean or flaxseed is (are) responsible for the protective effects observed in experimental animals and in limited studies in humans. Vegetable protein has been shown to have a beneficial effect on renal disease in animals and humans. Thus, the role of soy and flaxseed cannot be ruled out. Isoflavones and lignans are readily absorbed from the gut and converted to active metabolites, which may be partly responsible for the beneficial renal effects of soy protein and flaxseed. In addition, an interaction between type of protein and phytoestrogens is also possible. The biological actions of isoflavones and lignans have been well defined in different cell types in vitro and also in vivo, but how these compounds might reduce renal injury remains to be elucidated. Possible mechanisms include inhibition of cell growth and proliferation via ER-mediated mechanisms or non-ER-mediated pathways through inhibition of tyrosine protein kinases, modulation of growth factors involved in extracellular matrix synthesis and fibrogenesis, inhibition of cytokine-induced activation of transcription factors, inhibition of angiogenesis, antioxidative action, suppression of platelet activating factor and platelet aggregation, and immunomodulatory activity. To date, clinical trials in humans are few, of relatively short duration, and involve a small number of patients. Prospective randomized trials are needed to evaluate the long-term safety and effectiveness of dietary phytoestrogens on renal disease progression in patients with chronic renal failure.

Topics: Animals; Disease Progression; Estrogens, Non-Steroidal; Flax; Humans; Isoflavones; Kidney Failure, Chronic; Lignans; Phytoestrogens; Plant Preparations; Plant Proteins; Safety; Soybean Proteins; Treatment Outcome