Lack of Benefit of Early Intervention with Dietary Flax and Fish Oil and Soy Protein in Orthologous Rodent Models of Human Hereditary Polycystic Kidney Disease

Key Findings

Hereditary polycystic kidney disease (PKD) is characterized by renal cysts and often significant liver cysts. The two major types of PKD are autosomal dominant PKD (ADPKD) and autosomal recessive PKD (ARPKD). This study found that dietary oils enriched in omega-3 fatty acids provided early in the development of PKD displayed no benefits and possible negative effects on disease in both orthologous models of PKD studied. This lack of benefit in male PCK rats and in Pkd2^WS25/-mice is similar to the findings in female PCK rats. In non-orthologous models, fish oil has conflicting effects, with generally protective effects observed in the Han:SPRD-Cy rat while in the pcy mouse beneficial, detrimental and no effects have been observed. With respect to dietary protein source, there were no differences observed in the Pkd2^WS25/-mouse. While these studies provide no supporting evidence for dietary advice in the early stages of PKD to increase soy protein or oils enriched in omega-3 fatty acids, it is important to determine whether interventions in later stages of disease would benefit from these treatments. The amount of soy protein or omega-3 enriched oil also may influence the dietary effect, as the amounts used in the current diets are higher than what would be achievable in human diets. Evidence from non-orthologous models indicate that these dietary interventions may possibly be more effective during the progressive growth phase of cyst development.

ABSTRACT

Rationale for dietary advice in polycystic kidney disease (PKD) is based in part on animal studies that have examined non-orthologous models with progressive development of cystic disease. Since no model completely mimics human PKD, the purpose of the current studies was to examine the effects of dietary soy protein (compared to casein) or oils enriched in omega-3 fatty acids (fish or flax oil compared to soy oil) on early disease progression in two orthologous models of PKD. The models studied were Pkd2^WS25/- mice as a model of autosomal dominant PKD, and PCK rats as a model of autosomal recessive PKD. After 13 weeks of feeding, dietary fish (but not flax) oil resulted in larger kidneys and greater kidney water content in female Pkd2^WS25/- compared to control mice. After 12 weeks of feeding male PCK compared to control rats, both fish and flax compared to soy oil resulted in enlarged kidneys and livers, greater kidney water content and higher kidney cyst area in diseased rats. Dietary soy protein compared to casein had no effects in Pkd2^WS25/- compared to control mice. In PCK rats, kidney and liver histology were not improved, but lower proteinuria and higher urine pH suggest that soy protein could be beneficial in the long term. Therefore, in contrast to studies in non-orthologous models during the progressive development phase, these studies in orthologous PKD models do not support dietary advice to increase soy protein or oils enriched in omega-3 oils in early PKD.