Abstract: SA-PO839
Evaluation, Classification, and Identification of CKD Progression in Rhesus Macaques
Session Information
- CKD: Socioeconomic Context and Mobile Apps
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Yang, Zunyuan, Sichuan Primed Shines Bio-tech Co., Ltd., Chengdu, SiChuan, China
- Liang, Yinan, Sichuan Primed Shines Bio-tech Co., Ltd., Chengdu, SiChuan, China
- Gong, Li, Sichuan Primed Shines Bio-tech Co., Ltd., Chengdu, SiChuan, China
- Zeng, Wen, Sichuan Primed Shines Bio-tech Co., Ltd., Chengdu, SiChuan, China
- Hansen, Barbara, Dept Int Med, Univ of So Florida, Tampa, Florida, United States
Background
Chronic kidney disease (CKD) is characterized by progressive reduction in kidney function, and with accelerated cardiovascular disease and increased mortality. The goal of the present study was to characterize naturally occurring CKD in rhesus monkeys in comparison to the CKD of humans, to explore the relationship between CKD and CVD, and to evaluate the response of rhesus monkeys with combined CKD-CVD to the angiotensin receptor blocker, Valsartan.
Methods
Plasma biomarkers (Creatinine (Cr), Cystatin-C (CYSC), and Blood Urea Nitrogen (BUN)) were measured in 1198 adult rhesus monkeys (Macaca mulatta, 7-22 yrs). Four hr urine collections were obtained from 100 of these monkeys in order to measure urine albumin and urine creatinine for calculation of the urine albumin/creatinine ratio (UACR). Monkeys with eGFR (CKD-EPI) 30-59 ml/min/1.73m2 and/or UACR≥10mg/g were defined as having CKD (Grade G3a-3b). Blood pressure and cardiac function were measured, monkeys with LVEF<50%, e'<8 cm/s and E/e'>10 were defined as having CVD. A colony of 37 adult male monkeys received medical examinations and direct GFR measurements (Iohexol clearance). Eight monkeys with combined CKD-CVD were enrolled in the validation study and divided into the Valsartan group (n=4)(3 mg/kg, Bid) and the vehicle group (n=4). Cardiac function, blood pressure and UACR were measured before and after 8 weeks treatment. Cr, CYSC, BUN and eGFR were measured every 2 weeks.
Results
Among the 1198 adult rhesus monkeys studied, 52 monkeys (4.3%) had eGFR 30-59 ml/min/1.73m2 and/or UACR≥10mg/g. Among the 52 monkeys with CKD, 30 monkeys had confirmed CVD. With Valsartan treatment, average eGFR increased by 23.31%; average UACR decreased by 76.45%; and average SBP decreased by 14.40%. All of these biomarkers differed significantly compared to the vehicle group (p’s<0.05). The cardiac ultrasound parameters remained stable.
Conclusion
The 4.3% incidence of CKD in adult rhesus monkeys was similar to that in adult humans, and 58% of those with CKD also had CVD as in patients. Valsartan increased eGFR, and also decreased UACR and BP in monkeys. The extent of change in rhesus monkeys was similar to that observed in clinical trials. These monkey models, therefore, provide important new opportunities to understand the pathogenesis of CKD and predict the human response to new therapeutic agents.