Semester

Spring

Date of Graduation

2014

Document Type

Dissertation

Degree Type

PhD

College

Davis College of Agriculture, Natural Resources and Design

Department

Animal and Nutritional Sciences

Committee Chair

Janet C. Tou

Committee Co-Chair

Vagner A. Benedito

Committee Member

Brett P. Kenney

Committee Member

Joseph Moritz

Committee Member

Jiambo Yao

Abstract

Polycystic kidney disease (PKD) is a genetic disorder characterized by multiple benign cysts along the epithelial lining of the kidneys. As PKD progresses, cyst growth increases kidney volume, decreases renal function, and may eventually lead to end stage renal disease. In addition to renal manifestations, PKD patients are at risk of complications that include bone loss and polycystic liver disease (PLD). Currently, no genetic therapy or effective pharmacological treatments exist. Therefore, dietary intervention offers a potentially efficacious, cost-effective, and safe therapeutic option for PKD and PKD-related complications. Offering dietary treatment to attenuate PKD disease progression has the potential to improve renal function, preserve bone health, and to prevent PLD. Dietary soy protein has been shown to reduce cyst proliferation and growth and to enhance bone mass. Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA's) have anti-inflammatory properties. Dietary n-3 PUFAs have been shown to reduce PKD severity and may attenuate bone loss and PLD severity. Therefore, the objectives of this thesis was to investigate the role of dietary soy protein and/or n-3 PUFAs on PKD progression and severity and related complications of bone loss, and PLD using a pck rat model. Young (age 28 d) female pck rats were randomly assigned (n=12/group) to diets consisting of casein + corn oil (Casein + CO), casein + soybean oil (Casein + SO), SPI + soybean oil (SPI + SO) or SPI + 1:1 soybean/salmon oil (SPI + SB) for 12-weeks. Histological evaluation showed that all rats had renal and hepatic cysts regardless of the dietary group. Rats fed SPI+ SB diet had the highest (P = 0.03) renal and hepatic cortical cyst obstruction. Although, rats fed SPI+SB diet had the highest (P< 0.001) renal docosahexaenoic acid (DHA) and highest (P<0.001) hepatic eicosapentaenoic acid (EPA) and DHA content, this did not reduce inflammation. Gene expression of various transcription factors and inflammatory genes in the kidneys and liver was not significantly different among the dietary treatment groups. Histological evaluation of hepatic and renal fibrosis and gene expression of fibrosis were also not significantly different among the dietary treatment groups. However, rats fed SPI + SB diet had the highest (P < 0.01) serum blood urea nitrogen levels indicating reduced renal function. Rats fed SPI + SB diet also had the highest liver total lipid (P < 0.001) and steatosis (P = 0.003) suggesting disordered lipid metabolism. Rats fed SPI+SB diet had higher (P=0.01) calcium (Ca) and phosphorus (P) retention, but there were no significant differences in bone Ca, P, bone mass, bone microarchitecture or strength among the diet groups. Based on the results, dietary soy protein and/or n-3 PUFAs did not attenuate PKD progression and severity or related complications of bone loss and PLD in the female pck rat model of PKD. Furthermore, feeding SPI + SB diet was potentially detrimental on kidney function and liver metabolism in female pck rats.

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