What is your objective?

I will develop a faster, easier way to diagnose kidney disease in animals. Kidney disease, especially chronic kidney disease, is a "national disease that afflicts 1 in 8 people" in Japan, and animals also can develop kidney disease. The number of dogs and cats that have chronic kidney disease is increasing, and it is one of the most common causes of death.

The kidneys are a very difficult organ to heal, and treatment requires a great deal of time. In diagnosis and treatment of kidney disease, early discovery and stopping its progress are vital. Kidney disease is diagnosed by reading degradation of kidney function through blood or urine tests, but by the time kidney function has begun to degrade, the kidney cells are already undergoing pathological change. I believe that if it were possible to diagnose kidney disease much, much earlier, we would be able to stop its progress and save both humans and animals from this national disease.

My research focuses on the biological signs (biomarkers) that appear in urine and reflect the progress of kidney disease. We have discovered that people and animals afflicted with kidney disease show a specific nucleic acid in their urine. By analyzing the kidney disease models of animals and humans, as well as clinical samples from animals, we are evaluating their viability as diagnostic indexes in addition to seeking new biomarker candidates.

Kidneys of animals with kidney disease (histopathological image).

Animals, like people, can develop kidney disease. Kidney disease is diagnosed from blood test results (BUN, Cr ≒ The higher the number, the more kidney function has decreased).

The pictures on the left are of thin slices of animal kidneys, colored with dye and taken under an optical microscope. The shape of individual cells is easy to distinguish. The blue dots are cell nuclei.

The round cell groups (indicated with arrows and called glomeruli) that serve as blood filters appear larger in a dog with kidney disease than those in healthy dogs. The surrounding structures of the glomeruli in a cat with kidney disease appear different from a healthy cat. In this way, various changes in the kidney cells appear in cases of kidney disease.

 

What sort of research are you conducting?

1.    What are the biomarker candidates for kidney disease?
In my research, I am studying the nucleic acid (mRNA, microRNA) produced by kidney cells. I analyze the kidneys of kidney disease model mice, and find "nucleic acids that change in quantity" in early stages of kidney disease through genetic expression analysis. I am cyclopaedically selecting candidates from among roughly 30,000 types of mRNA and around 1,200 types of microRNA.
2.    What sort of kidney disease do kidney disease biomarker candidates reflect?
Kidneys are made up of at least 20 types of cells and are structurally more complex than other organs. I will study kidney disease model animals, as well as clinical samples from humans, dogs, and cats to determine what kidney cells produce biomarkers and how they are involved with kidney disease.
3.    How do kidney disease biomarkers appear in urine?
I will study the urine of kidney disease model animals, as well as humans, dogs, and cats to determine when and how biomarker candidates appear.

Biosynthesis and function of microRNA

microRNA is a single-strand RNA made up of 18 to 25 nucleic acids and is produced in the nucleus as a precursor. Precursors are cut by enzymes called Drosha and Dicers in the nucleus and cytoplasm, respectively, and mature.

mRNA is the blueprint for all proteins. Mature microRNA express their function by leading target mRNA to breakdown in cytoplasm.

In recent years, focus has been pointed at the role of microRNA in "cancer" and other diseases

 

What's next?

I believe there would be no progress in the field of medicine without progress in the field of veterinary medicine, and vice versa. I hope to research kidney disease with the basic methods of veterinary medicine, and contribute to the advancement of health in humans and animals.

Things like diagnostic standards, progression models, and susceptibility of kidney disease varies from race to race in both animals and humans. Such species difference is an issue for both medicine and clinical veterinary medicine, and is a barrier to diagnosis and treatment medicine development and research. Interestingly enough, the microRNA I am currently researching as a biomarker candidate has a homology among animal species and shows promise as a common biomarker for different species of animal.

At the same time, there are numerous causes and forms of kidney disease, like diabetic nephropathy, IgA nephropathy, lupus erythematosus nephritis, and HIV-associated nephropathy. Therefore, a biomarker and development of a convenient detection kit that applies to all types of kidney diseases in animals remain as an agenda. I hope to continue to identify biomarker candidates, and by combining the evaluation of multiple biomarkers, develop a next-generation kidney disease diagnosis such as "profile what is going on in the kidneys from the urine."