Biomarkers for ischemia and renal faiure

点击翻译按钮获取中文摘要

Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases including acute kidney injury and chronic kidney disease. Its early detection is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we demonstrate oxidative stress induces direct conformational change in tRNA structure and the change promotes subsequent tRNA fragmentation. Such tRNA changes occur much earlier than DNA damage. By various types of tissue damage model (ischemic reperfusion, toxic injury), the circulating tRNA-derivative levels are increased and the increase is more rapid than the known damage markers. In humans, the circulating tRNA-derivatives also increase under renal ischemia conditions. It also correlates with mortality in the general population (n=1,033 for 6.7 year follow up) . Therefore, tRNA damage reflects early oxidative stress damage and its detection is a useful tool for identifying organ damages and forming a clinical prognosis.