Significance of Kampo medicine in chronic kidney disease (CKD) and hypertension “1st International Symposium on Kampo Medicine”

Abstract

To The Editor Common pathological conditions are suggested to lead to various renal diseases such as diabetic nephropathy, chronic nephritis, and nephrosclerosis. Among these renal diseases, it is also necessary to keep in mind systemic complications such as those of the cardiovascular system. Therefore, they are collectively called chronic kidney disease (CKD). The severity classification of CKD consists of two components: the glomerular filtration rate (GFR) classification on the vertical axis, and the amount of urinary protein or urinary albumin on the horizontal axis. It has also been pointed out that the amount of urinary protein and the presence of hypertension have a significant effect on the prognosis of CKD progression. Kampo treatment is useful in many situations during the long disease course of CKD. In Kampo medicine, the pathophysiology of Oketsu (blood stasis) in CKD development is considered the background. At this symposium, an overview of Kampo treatment in dialysis-dependent and non-dialysis-dependent CKD, live imaging of anti-oketsu effects of Kampo prescriptions, and the effects of Kampo medicines on hypertension will be introduced. We hope that this session on CKD and hypertension will be beneficial for the audience and CKD treatment. The first presentation is “Clinical Aspects of NonDialysis-Dependent Chronic Kidney Disease (CKD).” We will outline traditional Kampo medicines for nondialysis-dependent CKD. In rat glomerulonephritis, saireito reduced urinary protein, and proliferating cell nuclear antigen (PCNA)and ED-1-positive cells (macrophages). It is reported that saireito involves suppression of the upregulation of the pro-inflammatory cytokines IL-1β and IL-6. Saireito is useful for non-dialysis-dependent CKD, which is mainly accompanied by proteinuria. Saireito is often used in combination with angiotensin II receptor blockers (ARBs); and there is room to consider tripartite combinations with mineral corticoid receptor antagonists (MRAs) [1]. Nephrosclerosis is usually caused by hypertension, and shichimotsukokato or hachimijiogan should be considered. In an irreversible rat glomerulonephritis model, shichimotsukokato suppressed elevation of systolic blood pressure and glomerular hypertrophy. Hachimijiogan is also used for diabetic nephropathy leading to advanced non-dialysis-dependent CKD. In order to judge the therapeutic effect, we need to apply traditional Kampo medicines to CKD, keeping in mind not only serum creatinine but also control of hypertension and minimization of urinary protein, which closely affect prognosis. When hypokalemia develops, it is necessary to consider discontinuing the licorice-rich preparation, or using MRAs in addition. The second presentation is “Live Imaging of AntiOketsu Effects of Kampo Prescriptions Used for Chronic Kidney Disease.” Oketsu (blood stasis) is a characteristic condition of Kampo and includes multiple aspects of hemodynamic disorders in arteries, arterioles and capillaries. Abnormalities of glomerular microcirculation in CKD are also included in this concept, and thus, Kampo prescriptions with anti-oketsu effects are theoretically effective in CKD treatment. We clarify the modern pharmacological background of traditional Kampo therapeutic theories by live imaging of the anti-oketsu effects of various Kampo prescriptions. In the microcirculation, differences in the pharmacological effects of various anti-oketsu Kampo prescriptions are apparent in differences in the target vessels: tokakujyokito has a vasodilative solid effect on the arteries with a short onset; keishibukuryogan induces vasodilation in arterioles with slower onset; and tokishakuyakusan enhances blood flow velocity in the capillaries, with a slow onset of effect but long-lasting action [2]. These results are generally consistent with the clinical selection of Kampo prescriptions and can provide a pharmacological background to the traditional therapeutic strategies of Kampo, based on sho. Nitric oxide (NO) also defines the characteristics of each prescription. Keishibukuryogan and kamishoyosan enhance vascular endothelial NO production, while goshajinkigan inhibits this. In addition, we have found that the anti-oketsu Kampo prescriptions improve Received: 18 May 2022 Revised: 10 June 2022 Accepted: 16 June 2022