Abstract: FR-PO180
Evaluation of Urinary NKCC2 and NCC in Rats with AKI Induced by Candesartan Plus Low-Salt Diet in Rats
Session Information
- AKI: Mechanisms
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Xie, Anni, The Department of Nephrology, The Affiliated BenQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, China
- Xiao, Leijuan, The Department of Nephrology, The Affiliated BenQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, China
- Zhang, Mingzhuo, The Department of Nephrology, The Affiliated BenQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, China
- Duan, Haonan, The Department of Nephrology, The Affiliated BenQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, China
- Ren, Zhiyun, The Core Laboratory for Clinical Research, The Affiliated BenQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, China
- Wang, Ping, The Core Laboratory for Clinical Research, The Affiliated BenQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, China
- Jia, Yutao, The Department of Nephrology, The Affiliated BenQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, China
- Liu, Mingda, The Core Laboratory for Clinical Research, The Affiliated BenQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, China
- Lou, Jizhuang, The Department of Nephrology, The Affiliated BenQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, China
- Wang, Xiaoyan, The Department of Nephrology, The Affiliated BenQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, China
Background
Dietary-salt-restriction and angiotensin-II-receptor-1-blockade are often suggested to the patients with renal and cardiovascular diseases.
Methods
We studied the dietary effects of low-salt(LS, 0.01%NaCl), normal-salt(NS,0.8%NaCl) and high-salt(NS, 2%NaCl) on renal functions and urinary exosomal renal sodium-potassium-chloride-cotransporter-2(NKCC2) and sodium-chloride-cotransporter(NCC) in rats treated with candesartan(1mg/kg/day,IP), a common angiotensin-II-receptor-1-blocker, to determine if the combination of the two strategies were beneficial and how to detect renal dysfunction early.All rats were treated with candesartan. Model I: LS, NS and HS were fed rats respectively for 7 days. Model II: NS was pretreated for 4 days before switching to LS for 3 days in experimental group. Model III: similar as model II, but the diet was switched back to HS for extra 3 days.
Results
Serum creatinine (SCr) increased on day 7(55.83±6.46) of model I and on day 3 of model II(56.56±8.28). Urinary exosomal NKCC2(905.76±127.59, % of day0) and NCC(637.51±87.35) increased on day 7 in Model I. In model II, urinary exosomal NKCC2(908.12±227.46, % of day 0) started to increase on day 1, which was 2 days earlier than increased SCr, and kept high for 3 days. NCC(160.6±23.85) was increased only at day 1. In model III, switching diet back to HS reversed the increases of SCr(39.40±2.56 vs 34.80±1.28,umol/L,day3 vs day+3, p<0.05) and urinary exosomal NKCC2(43.54±17.75,% of day3) and NCC(3.60±0.87,% of day3). NKCC2 was located in the renal apical membranes of rat outer medullary tubules while NCC was in the apical side of certain cortical tubules next to glomeruli, in agreement with their respective distribution in kidney. Their protein expressions were not affected in whole kidney homogenates except an increase of NKCC2 in model I.
Conclusion
Thus, low salt diet induces acute kidney injury in candesartan-treated rats which can be reversed by a moderate salt load. Urinary exosomal NKCC2 and NCC may be considered as early biomarkers for detection of AKI accordingly.
Funding
- Government Support – Non-U.S.