Compound α-keto acid tablet supplementation alleviates chronic kidney disease progression via inhibition of the NF-kB and MAPK pathways

Autor: Li Li, Kun Qian, Octavia Li-Sien Chong Lee Shin, Han Zhu, Fan Zhu, Ying Yao, Rui Zeng, Wangqun Liang, Huzi Xu, Min Wang, Hanjing Zhou, Hui Gao, Zhi Zhao, Chunxiu Zhang
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Exacerbation
medicine.medical_treatment
lcsh:Medicine
Apoptosis
Gastroenterology
0302 clinical medicine
Renal function decline
Fibrosis
Kidney
Hazard ratio
NF-kappa B
General Medicine
Middle Aged
Keto Acids
Nephrectomy
Ischemia–reperfusion
medicine.anatomical_structure
Reperfusion Injury
030220 oncology & carcinogenesis
Disease Progression
Female
Tablets
Compound α-ketoacid tablets
Progression of chronic kidney disease
medicine.medical_specialty
MAP Kinase Signaling System
Renal function
General Biochemistry
Genetics and Molecular Biology
End stage renal disease
03 medical and health sciences
Internal medicine
Diet
Protein-Restricted
medicine
Animals
Humans
Renal Insufficiency
Chronic
Probability
Inflammation
business.industry
Research
lcsh:R
medicine.disease
Survival Analysis
Mice
Inbred C57BL
030104 developmental biology
Dietary Supplements
business
Kidney disease
Zdroj: Journal of Translational Medicine, Vol 17, Iss 1, Pp 1-15 (2019)
Journal of Translational Medicine
ISSN: 1479-5876
Popis: Background Keto-analogues administration plays an important role in clinical chronic kidney disease (CKD) adjunctive therapy, however previous studies on their reno-protective effect mainly focused on kidney pathological changes induced by nephrectomy. This study was designed to explore the currently understudied alternative mechanisms by which compound α-ketoacid tablets (KA) influenced ischemia–reperfusion (IR) induced murine renal injury, and to probe the current status of KA administration on staving CKD progression in Chinese CKD patients at different stages. Methods In animal experiment, IR surgery was performed to mimic progressive chronic kidney injury, while KA was administrated orally. For clinical research, a retrospective cohort study was conducted to delineate the usage and effects of KA on attenuating CKD exacerbation. End-point CKD event was defined as 50% reduction of initial estimated glomerular filtration rate (eGFR). Kaplan–Meier analysis and COX proportional hazard regression model were adopted to calculate the cumulative probability to reach the end-point and hazard ratio of renal function deterioration. Results In animal study, KA presented a protective effect on IR induced renal injury and fibrosis by attenuating inflammatory infiltration and apoptosis via inhibition of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. In clinical research, after adjusting basic demographic factors, patients at stages 4 and 5 in KA group presented a much delayed and slower incidence of eGFR decrease compared to those in No-KA group (hazard ratio (HR) = 0.115, 95% confidence interval (CI) 0.021–0.639, p = 0.0134), demonstrating a positive effect of KA on staving CKD progression. Conclusion KA improved IR induced chronic renal injury and fibrosis, and seemed to be a prospective protective factor in end stage renal disease.
Databáze: OpenAIRE
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