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논문분류	춘계학술대회 초록집
제목	The role of Lactic Acidosis on Reneal Fibrosis and its dysfunction in DKD
저자	Won-Ho Kim
출판정보	2023; 2023(1):
키워드
초록	Diabetes characterized by hyperglycemia and insulin resistance is the most common cause of chronic kidney disease (CKD) however, the metabolic factors that promote diabetic renal failure includingfibrosis are unclear. We investigated the metabolite changes in animal and human subjects with diabeticCKD (dCKD) and the role of lactate dehydrogenase A LDHA-mediated lactate production in renalfibrosis and dysfunction. Streptozotocin (STZ; 60 mg/kg)-induced dCKD rats and clinical information and samples from dCKDpatients (n=53) and healthy participants (n=16) were used. Diabetic renal fibrosis and dysfunction wereclosely associated with significant changes in the metabolites involved in the top-ranked functionalpathways. Among them, lactate, a glycolysis end product, was significantly increased in STZ-induced diabetic rats and dCKD patients. Increased lactate positively correlated with reduced Wilms’ tumor-1 (WT-1) expression and increased LDHA expression, mitochondrial andoxidative damage, resulting in renal fibrosis. TGF-β1-mediated renal fibrosis depends on lactateproduction, which was significantly attenuated by inhibiting glycolytic and LDHA lactate regulatorypathways. dCKD patients showed a significant negative correlation between urinary lactate levels orLDHA expression and the estimated glomerular filtration rate (eGFR), which were closely associatedwith an increase in glycated hemoglobin (HbA1c). In conclusion, increased renal or urinary lactatemetabolites are associated with alterations in renal metabolic homeostasis and may serve as earlypredictive biomarkers for the progression of d CKD.
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