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

Abstract

Hereditary polycystic kidney disease (PKD) is characterized by countless renal cysts and often also displays significant liver cysts. Due to lack of a cure and the inefficacy of current treatments in delaying renal replacement therapy, there is much interest in the potential for dietary approaches to slow PKD progression. Rationale for current dietary advice is based in part on animal studies that have examined primarily male animals and non‐orthologous models with rapidly developing cystic disease. For example, in Han:SPRD‐Cy rat and pcy mouse models, soy protein feeding results in lower kidney size and water content, along with reduced cyst growth and fibrosis. Dietary flax oil also has similar benefits in both of these models. However, fish oil appears to have beneficial effects in the Han:SPRD‐cy rat, but not always in the pcy mouse.Since dietary studies have not used orthologous models of PKD, the objective of the current studies were to examine the effects of dietary soy protein or oils enriched in omega‐3 fatty acids on early disease progression in orthologous models. These were male and female Mx1Cre+Pkd1flox/flox (Pkd1) mice induced at 5 and 1 weeks of age and Pkd2WS25/− (Pkd2) mice, as models of autosomal dominant PKD (ADPKD), and male PCK rats as a model of autosomal recessive PKD (ARPKD). The control diet was the AIN93G diet that has casein as the protein source and soy oil as the lipid source. Experimental groups were given a comparison diet which contained either an equivalent amount of protein as soy protein that replaced the casein, or either flax oil or fish oil that replaced 80% of the soy oil. Dietary treatments were for 6 weeks (Pkd1 mice induced at 1 week of age), 16 weeks (Pkd1 mice induced at 5 weeks of age), 13 weeks (Pkd2 mice) or 12 weeks (PCK rats). Body weight, urine volume and pH and water disappearance were measured during the feeding phase. Kidney, liver and body weights were recorded at termination. Kidney and liver water content was determined by lyophilisation and cyst area and fibrosis were determined by histology.Dietary fish and flax compared to soy oil resulted in less kidney water content in both sexes in Pkd1 mice induced at 5 weeks, but had no effect on renal cyst area or fibrosis in these mice, and no effects on any disease parameters in Pkd1 mice induced at 1 wk. In Pkd2 mice, dietary fish (but not flax) oil resulted in more kidney water content (only) in female Pkd2 mice, but did not affect any other disease parameters. In PCK rats, both fish and flax compared to soy oil resulted in higher kidney water content, as well as cyst area. Dietary soy protein (cf. casein) had no effects on kidney water content or cyst area, and no dietary treatment altered these parameters in the livers of all models.Therefore, in contrast to studies in non‐orthologous models during the rapid cyst growth phase, these studies in male and female orthologous PKD models do not support dietary advice to increase soy protein or oils enriched in omega‐3 oils in early PKD.Support or Funding InformationCanadian Institutes of Health Research