An Interview with Professor Sadayoshi Itoh on the Reception of the American Heart Association Arthur C. Corcoran Memorial Lecturer Award
"Measuring the Health of the Brain Based On the Functioning of the Kidney"

Predicting brain disease from kidney anomalies

Professor Itoh:
Also, in 2002, a concept of chronic kidney disease was introduced. Chronic kidney disease is a term that collectively refers to abnormal conditions of the kidney such as a glomerular filtration rate of less than 60% of the normal level (100 ml/minute) and a very slight amount of protein excreted into the urine. Epidemiological studies have shown that patients with chronic kidney disease are more likely to develop stroke or myocardial infarction than to come to receive dialysis treatments. The biggest mystery of chronic kidney disease is that, even when glomerulus filtering is normal, a person is prone to develop stroke or myocardial infarction if a very tiny amount of urine protein is present (10 mg in the form of albumin). Come to think of it, the normal glomerular filtration rate (GFR) is 150 liters a day, and the amount of protein contained in the form of albumin is as large as 6 kilograms. Of all this protein, how is a mere 10 mg of it leaking into the urine related to diseases of blood vessels in the brain and heart?

One day, one of my coworkers asked me, "Professor Itoh, when albumin leaks, is there any difference in terms of where it leaks?" In that instant, the vascular structure of the brain overlapped that of the kidney in my mind (Figure 3). When the thick blood vessels entering the kidney are exposed to high blood pressure, the thin blood vessels located near those thick blood vessels are also exposed directly to high blood pressure and damaged (A in Figure 3). Albumin leaks from such damaged vessels. The thin blood vessels far from the thick blood vessels, on the other hand, are not damaged because the blood pressure drops before blood reaches there (B in Figure 3). Since a small amount of albumin leaking from the few damaged glomeruli near the thick blood vessels is diluted by the normal urine filtered by the many other glomeruli, substantially decreasing the concentration of albumin in the urine and hence a slight amount of albumin. This means that the presence of albumin in the urine, albeit in small amounts, provides evidence that afferent arterioles near a thick artery in the kidney is damaged. The fact that a vascular anomaly is occurring in the kidney suggests that the blood vessels in the brain that has exactly the same structure as the kidney are prone to be damaged as well (Figure 3, bottom).

Then, why does our body have such a fragile vascular structure? I think that it probably concerns the evolution of organisms. When the body has this mechanism, it can send blood to its vital organs, such as the brain and kidney, even if the blood pressure lowers due to trauma or other cause. In other words, the reason why thick blood vessels are connected to thin blood vessels is to protect the body against low blood pressure. Today, the function to withstand low blood pressure acquired through the long process of evolution causes blood vessels to be damaged by high blood pressure. How strange!

PR Office:
The story about the relationship between the evolution of humanity and low and high blood pressures is very interesting.

Professor Itoh:
Thanks to the discovery of this mechanism, if albumin is contained in the urine, no matter how small its amount is, we can check for other diseases and start treatment early. A tiny amount of albumin is present in a patient's urine. The patient may try to play it down as no big deal, but a slight amount does not necessarily mean a minor disorder. The fact that the blood vessels in the kidney are damaged suggests a high possibility that the blood vessels in the brain are also damaged. Leaving this situation as it is could potentially lead to brain disease.

PR Office:
By checking the urine, you can find out the conditions of the brain.

Professor Itoh:
This finding is increasingly recognized in society these days. I call this entity a strain vessel*5, because these blood vessels (A in Figure 3) are under extremely high strain. They are thin arteries (whose thickness is a tenth of that of a hair) that are exposed to and endure a high pressure. On top of that, the pressure is of pulsating nature (this is because the heart pulsates). When the blood pressure becomes low, the blood stream can be maintained by dilating moderately strained blood vessels. When the blood pressure becomes high, on the other hand, it is necessary to put blood vessels under higher strain. If this excessively strained condition continues, blood vessels are gradually damaged, resulting in protein leaking and the brain suffering stroke.

PR Office:
As you continue with your research, you discover new mechanisms one after another.

igure 3. Vascular structure of the kidney and that of the brain The branches of thin blood vessels near the thick blood vessels are exposed to high pressure. The further thin blood vessels get from the thick blood vessels, the lower the pressure on these thin blood vessels becomes. Even if the glomeruli of A in the kidney are damaged by high blood pressure and albumin leaks into the urine, it is diluted by the large volume of urinary water from the majority of normal glomeruli of B, resulting in only a small amount of albumin being found in the urine. However, a slight amount of albumin in the urine indicates that the blood vessels in the brain having the same structure as the kidney are at a high risk of being damaged.

*5: Strain vessel: A blood vessel under strain

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