(P18-009-24) Comparing Resistant Starch and a Renin-Angiotensin System Inhibitor's Renoprotection Effects on Vitamin D Homeostasis and Proteinuria in a Preclinical Type 2 Diabetes Model

Objectives: Diabetic kidney disease (DKD) is one of the most prevalent complications of diabetes and currently the leading cause for kidney disease. DKD affects the integrity of the kidney over time, leading to decreased filtration capacity and extensive kidney damage. Previous findings from our laboratory have established that a diet high in resistant starch (RS) decreased proteinuria and urinary vitamin D loss, which are symptoms of kidney deterioration, in both type I and II diabetic rats. The aim of this study was to investigate the mechanisms behind our observations by using a combination of low to moderate doses of RS diets and captopril (cap), an angiotensin-converting enzyme (ACE) inhibitor that has been shown to help maintain kidney integrity, to type II diabetic rats.

Methods: Zucker diabetic fatty (ZDF) rats (n=48, 5 wk old) were randomly assigned to one of three experimental diets: AIN-93G with 0% RS control diet, AIN-93G with 5% RS or 10% RS. Diet adjustments were made to accommodate RS at the expense of cornstarch, so the macronutrient profiles of all diets were equal. ZDF rats were also administered intraperitoneal injections with either cap (0.25mg/kg of body weight, i.p.) in a saline-citrate vehicle, or vehicle injections for 7 weeks. To serve as a baseline control, lean Zucker rats (n=7) were assigned to a standard AIN-93G diet and administered vehicle during the same timeframe.

Results: ZDF rats that were fed a 10% RS and provided cap injections exhibited decreased albuminuria (30%), proteinuria (63%), and lower urinary excretion of vitamin D binding protein (12.7%). This was reflected in a 62% increase in serum 25-hydroxyvitamin D concentrations, compared to diabetic control rats. Relative abundance of kidney proteins involved in renin-angiotensin system (RAS) activity showed that the same intervention group exhibited a 33.3 % decrease in aldosterone synthase expression compared to the diabetic control group. ZDF rats fed a 5% RS diet and injected with placebo also exhibited a significant decrease in the expression of kidney injury molecule-1.

Conclusions: Our results indicate that a combined intervention of low-to-moderate dose of RS and captopril may each protect kidney integrity in diabetic rats in a similar manner by modulating the RAS.

Funding Sources: Our work was funded by a USDA-NIFA grant to MR.