Abstract: FR-PO178
Changes of Kidney and Urinary Klotho Reflect the Involvement of Distal Convoluted Tubules in Lipopolysaccharide (LPS)-Induced AKI 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
- Wang, Weiwan, The Core Laboratory, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
- Zhang, Mingzhuo, The Core Laboratory, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
- Xie, Anni, The Core Laboratory, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
- Liu, Mingda, The Core Laboratory, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
- Jia, Yutao, The Core Laboratory, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
- Duan, Haonan, The Core Laboratory, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
- Wang, Xiaoyan, The Core Laboratory, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
Background
Sepsis is one of the common causes for acute kidney injuries (AKI).
Methods
To seek a noninvasive but early biomarker, we determined klotho, an anti-aging protein secreted by renal distal convoluted tubules, in kidneys and urines from sepsis-like AKI rats at 6, 12, 24-h respectively after a single intraperitoneal injection of LPS at 5 mg/kg.
Results
The LPS-rats exhibited similar appearances, body weights and urine volumes as the controls. Serum creatinine concentration was not altered at 6, and 12-h but elevated at 24h (51.0±5.0 vs 31.0±1.6, mmol/L??? n=5/group, p<0.05). Compared with baseline (28.8±1.7, ng/ml), serum klotho declined in the rats at 12 (18.5±3.4) and 24h (19.6±3) but not 6h while serum kidney-injury-molecular-1，cystatin C were not changed at all time points. Klotho was detected in rat renal distal convoluted tubules and colocalized with positive staining of NCC at apical membranes. Renal klotho was lowered at 6 (66.8±6.4, % of controls, same as below), 12 (38±1.6) and 24-h (40.5±6.2) in LPS rats than controls. Klotho mRNA expressions were decreased at 6 (27.9±4.6), 12 (36.2±10.7) and 24-h (22.2±3.8). Furthermore, klotho in urinary exosomes was much enriched relative to original urines. Urinary exosomal klotho excretions, corrected by corresponding creatinine concentrations, were elevated at 6 (245.2±56.2), 12-h (246±53), not 24h in LPS rats relative to vehicle controls. NCC in kidneys was unchanged but increased in urinary exosomes at 6 (394.01±137.57) and 12-h (658.83±220.56).
Conclusion
Thus, LPS impaired renal functions including synthesis and production of klotho from distal convoluted tubules while the decrease of klotho in kidney is followed by its decrease in serum. However, the rises of urinary exosomal klotho and NCC may reflect their leakages from kidney into urines during the AKI process and could be considered as early biomarkers for the septic AKI.