Preventing the onset of diabetes-induced chronic kidney disease during prediabetes: The effects of oleanolic acid on selected markers of chronic kidney disease in a diet-induced prediabetic rat model

Background: The prevalence of prediabetes correlates with increased incidence of chronic kidney disease (CKD). This study was aimed at investigating the effects of oleanolic acid (OA) on markers associated with CKD in the prediabetic rat model. Methods: Prediabetes was induced by exposing male Sprague Dawley rats (150-180 g) to high-fat high- carbohydrate (HFHC) diet for 20 weeks. The prediabetic animals were further subdivided according to their treatment and treated for 12 weeks with either OA (80 mg/kg p.o) or metformin (500 mg/kg p.o) both with and without dietary intervention. 24 h fluid intake and urine output were measured every fourth week of the treatment period while the urine samples were also used for podocin quantification through PCR. The animals were then sacrificed with urine, plasma and kidneys being harvested for biochemical analysis including the measurement of aldosterone, kidney-injury-molecule-1(KIM-1), blood and urine electrolytes, estimated glomerular filtration rate (eGFR), and albumin/creatinine (Alb/Cr) ratio. Results: This study observed that OA could reduce oxidative stress in the kidney while restoring plasma aldosterone and KIM-1 as well as urine electrolytes which were found to be augmented in prediabetic animals. This also correlated with normalization of GFR and Alb/Cr ratio in the OA-treated groups in both the absence and presence of dietary intervention. Conclusions: These findings suggest that OA can ameliorate renal complications in a prediabetic rat model. However, more research is needed for the elucidation of molecular mechanisms behind these effects.