Reverse translational research of autophagy and metabolism in kidney disease: Oshima Award Address 2018

The management of chronic kidney disease (CKD) has been a great challenge. Focusing on the difficulty to predict the prognosis of CKD, we initially conducted a series of observational studies, and evaluated the prognostic impacts of cardiac, diabetic, kidney, as well as senescent profiles, on CKD. Aiming to protect tubular inflammatory lesions, we studied the roles of autophagy, a process of auto-degradation for cellular homeostasis, in kidney diseases. After having determined its protective role, the proceedings of our autophagy studies are now revealing the mechanisms whereby autophagy protects kidney; autophagy protects kidney from DNA damage, and oxidative and metabolic stress. These emerging roles of autophagy converged on the concept that quality control of organelles (mitochondria and lysosomes), as well as the regulation of metabolism, are the key to protect kidney from diseases, ranging from CKD, acute kidney injury (AKI) to aging kidney. To broaden the clinical potential of autophagy, some cellular and molecular studies were followed up to identify the specific targets of autophagy. Having encountered the critical roles of metabolism in kidney diseases, we conducted a subset of clinical studies, and found that d-amino acids, the chiral derivatives of l-amino acids, can predict the prognosis of CKD. d-Amino acids, normally present in only trace amounts in humans, would be potential candidates for the biomarkers in CKD. The intersections between clinical and basic research provided us a potential approach for the better kidney management, reconfirming the aspects that the reverse translational study is an excellent method for the kidney research.