ABSTRACT
It is recently known that the kidney and brain have a very rich distribution of blood vessels, and the histological structures of micro-vessels are very similar. Therefore, a number of studies have reported that renal diseases like chronic kidney disease (CKD) caused by various causes have a very close relationship with the occurrence of neurodegenerative diseases. On the other hand, since diabetic nephropathy, which is caused by chronic inflammation, such as diabetes, often shows very different prognoses even in patients at the same clinical stage, the judgment of their disease prognosis will have a critical meaning in clinical practice. Recently, many studies of cerebro-renal interaction have been reported using experimental animals. The discovery of common biomarkers found in both organs can predict the prognosis of renal disease and the possibility of neurodegenerative disease progression. More associations can be found with novel common biomarkers found in the brain and kidneys that seem entirely unrelated. In that case, it will ultimately be a research field that can expand predictive models of patients' complex diseases through these biomarkers in clinical practice. It is presented biomarkers such as α-klotho, Nephrin, and Synaptopodin. These markers are observed in both the brain and kidney, and it has been reported that both organs show a very significant change in function according to their expression. Even though the brain and kidneys perform very independent functions, it is thought that it has a crucial diagnostic significance that the genes commonly expressed in both organs are functionally effective. With the discovery of novel biomarkers that share cerebro-renal interactions at the early stage of diabetic nephropathy, physicians can predict post-clinical symptoms and prevent severe neurodegenerative and cerebrovascular diseases. Therefore, further study for the diseases of these two organs in laboratory animals means that the field of research on this relationship can be expanded in the future. In the future, more attention and research will be needed on the possibility of prediction for the prevention of neurological diseases caused by CKD in disease animal models.
ABSTRACT
One third of the patients with chronic kidney disease (CKD) develop cognitive impairment, which is also an independent risk factor for mortality. However, the concise mechanism of cerebro-renal interaction has not been clarified. The present study examines the effects of uremic toxins on neuronal cells and analyzes the pathological condition of the brain using mouse hippocampal neuronal HT-22 cells and adenine-induced CKD model rats. Among the uremic toxins analyzed, indoxyl sulfate, indole, 3-indoleacetate, and methylglyoxal significantly decreased viability and glutathione level in HT-22 cells. The mixture of these uremic toxins also decreased viability and glutathione level at a lower dose. Adenine-induced CKD rat showed marked renal damage, increased urinary oxidative stress markers, and increased numbers of pyknotic neuronal cells in hippocampus. CKD rats with damaged hippocampus demonstrated poor learning process when tested using the Morris water maze test. Our results suggest that uremic toxins have a toxic effect on hippocampal neuronal cells and uremic CKD rats shows pyknosis in hippocampus.