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.

Tamio Yamaguchi,Jessay G Devassy,Harold M Aukema,Md Monirujjaman,Melissa Gabbs,David Long

doi:10.1371/journal.pone.0155790

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 Pkd2WS25/- 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 Pkd2WS25/- 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 Pkd2WS25/- 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.

Highlights

Hereditary polycystic kidney disease (PKD) is characterized by countless renal cysts and often displays significant liver cysts
80–85% of autosomal dominant PKD (ADPKD) is caused by mutations in PKD1, the gene for polycystin 1, and the remaining 15–20% of cases
All mice were given diets based on the American Institute of Nutrition (AIN) 93G standard diet for laboratory rodents [17], which has casein as the standard protein source and soy oil as the standard oil

Summary

Introduction

Hereditary polycystic kidney disease (PKD) is characterized by countless renal cysts and often displays significant liver cysts. The two major types of PKD are autosomal dominant PKD (ADPKD) and autosomal recessive PKD (ARPKD). 80–85% of ADPKD is caused by mutations in PKD1, the gene for polycystin 1, and the remaining 15–20% of cases. Dietary Effects in Models of Polycystic Kidney Disease studentship to MG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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Conclusion