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

• Published in: Journal of translational medicine Vol. 17; no. 1; p. 122
• Main Authors: Wang, Meng, Xu, Huzi, Chong Lee Shin, Octavia Li-Sien, Li, Li, Gao, Hui, Zhao, Zhi, Zhu, Fan, Zhu, Han, Liang, Wangqun, Qian, Kun, Zhang, Chunxiu, Zeng, Rui, Zhou, Hanjing, Yao, Ying
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.04.2019; BioMed Central; BMC
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Chronic kidney failure; Compound α-ketoacid tablets; Demographics; Development and progression; Diabetes; Diet; Diet therapy; Diet, Protein-Restricted; Dietary Supplements; Disease Progression; Epidermal growth factor receptors; Female; Fibrosis; Genetic aspects; Glomerular filtration rate; Health aspects; Health hazards; Humans; Inflammation; Inflammation - pathology; Inhibition; Ischemia; Ischemia–reperfusion; Keto Acids - pharmacology; Keto Acids - therapeutic use; Ketogenic diet; Kidney diseases; Kidneys; Kinases; Laboratory animals; Male; MAP kinase; MAP Kinase Signaling System - drug effects; Medical research; Metabolism; Mice, Inbred C57BL; Middle Aged; Nephrectomy; NF-kappa B - metabolism; NF-κB protein; Nutrition research; Patients; Probability; Progression of chronic kidney disease; Protein kinase; Proteins; Renal function; Renal function decline; Renal Insufficiency, Chronic - drug therapy; Renal Insufficiency, Chronic - etiology; Renal Insufficiency, Chronic - pathology; Renal Insufficiency, Chronic - physiopathology; Reperfusion; Reperfusion Injury - complications; Supplements; Surgery; Survival Analysis; Systematic review; Tablets; Beijing China; United States > US; China; Germany; Compound α-ketoacid tablets; Progression of chronic kidney disease; Ischemia–reperfusion; Renal function decline
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-019-1856-9

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. 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. 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. KA improved IR induced chronic renal injury and fibrosis, and seemed to be a prospective protective factor in end stage renal disease.