Department of Nephrology

Kidney function, with a focus on proximal tubular function and sex differences in kidney disease.

The Japanese Society of Internal Medicine
The Japanese Society for Dialysis Therapy (JSDT)
The Japanese Society of Nephrology (JSN)
Japan College of Rheumatology (JCR)
The Japanese Society for Biomedical Mass Spectrometry (JSBMS)

Chronic Kidney Disease (CKD) is a significant national health issue in Japan, affecting one in eight adults. Sex differences in CKD progression have been noted—specifically, males are disproportionately represented among those initiating dialysis at end-stage renal disease—however, the underlying mechanisms remain largely unclear. Therefore, elucidating these sex differences and establishing sex-specific approaches to CKD diagnosis and treatment are urgent priorities.
The kidneys filter blood to excrete waste products as urine. The proximal tubule is the first segment through which the primary urine passes after filtration by the glomerulus. This segment is responsible for reabsorbing essential substances from the primary urine, including amino acids, glucose, electrolytes, and water. The proximal tubule is also notably rich in mitochondria and exhibits highly active energy metabolism. Previous studies have revealed that the proximal tubule contributes to the pathophysiology of CKD and Acute Kidney Injury (AKI) not only by reabsorbing essential substances, but also by taking up certain nephrotoxic compounds. In addition, the proximal tubule is involved in the reabsorption of specific uremic toxins that accumulate during CKD, contributing to atherosclerosis and dialysis-associated amyloidosis. It has also been reported that alterations in the gut microbiota during CKD promote the production and accumulation of these uremic toxins.
Based on this background, this study aims to analyze the role of the proximal tubule in kidney disease from the perspectives of mitochondrial function, uremic toxins, the gut microbiota, and sex differences. Our ultimate goal is to develop novel therapeutic strategies for kidney disease by targeting the functional regulation of the proximal tubule.