The number of human patients with chronic kidney disease (CKD) is increasing with the aging of society. Similarly, the incidence of CKD in animals, especially dogs and cats, is also increasing with the aging of individuals.
In order to achieve “One Health” for humans and animals, it is important to study useful targets for the diagnosis and treatment of CKD in these mammals. However, the species specific-differences of renal pathogenesis complicate it; dogs tend to show renal glomerular lesions as humans, but most cats manifest tubulointerstitial lesions. Therefore, there is a need to develop therapeutic and diagnostic methods based on the elucidation of species-specific renal pathogenesis, and we are conducting comprehensive research targeting human as well as model animals and companion animals.
In particular, we continue to focus on the unique role of “urine” in various kidney diseases. Our previous studies have shown that urine from model or companion animals with CKD contains candidate disease markers such as cytokines and non-coding RNAs, which are involved in their renal pathogenesis. In addition, as for a unique recent topic, we found that urine is a biological fluid that alters the local immune status of urogenital tissues. Briefly, tertiary lymphoid structures in the renal pelvis, called “urinary tract-associated lymphoid structures (UTALSs)”, were formed in humans and mice with chronic nephritis, regardless of infections. In the development of UTALSs, aging and altered immune status as wells as urine played a role in UTALS formation. In a nephritis mouse model, urine leaked from the lumen of the renal pelvis into its parenchyma. Based on obtained findings, we consider that altered urine-urothelium barrier-based UTALS formation may represent a novel mechanism underlying the pathogenesis of chronic nephritis, regardless of urinary tract infection.
Further studies focusing on urinary biomarker candidates and unique roles of urine in renal pathogenesis would be crucial for clinical development and understanding the mechanism of kidney disease progression, to realize One Health in the field of human and animal nephrology.