Traditional Chinese Medicine in the Treatment of Chronic Kidney Diseases: Theories, Applications, and Mechanisms

Abstract

Chronic kidney disease (CKD) is a common and progressive disease that has become a major public health problem on a global scale. Renal fibrosis is a common feature in the pathogenesis of CKD, which is mainly related to the excessive accumulation and deposition of extracellular matrix caused by various inflammatory factors. No ideal treatment has yet been established. In recent years, based on the traditional Chinese medicine (TCM) theory of CKD and its molecular mechanism, clinical evidence or experimental studies have confirmed that a variety of Chinese materia medica (CMM) and their effective components can delay the progress of CKD. TCM believes that the pathogenesis of CKD is the deficiency in the root and excess in the branch, and the deficiency and excess are always accompanied by the disease. The strategies of TCM in treating CKD are mainly based on invigorating Qi, tonifying the kidneys, promoting blood circulation, removing stasis, eliminating heat and dampness, removing turbidity, and eliminating edema, and these effects are multitargeted and multifunctional. This review attempts to summarize the theories and treatment strategies of TCM in the treatment of CKD and presents the efficacy and mechanisms of several CMMs supported by clinical evidence or experimental studies. In addition, the relationship between the macroscopic of TCM and the microscopic of modern medicine and the problems faced in further research were also discussed.

Keywords: Chinese materia medica; chronic kidney disease; intervention mechanism; reinforcing deficiency and purging excess; renal fibrosis; traditional Chinese medicine.

FIGURE 1

The corresponding relationship between the pathogenesis of the TCM theory and the modern medicine theory. (A) Characteristics of TCM pathogenesis in the process of chronic kidney disease. In the early stage of CKD, although the spleen and kidneys are insufficient, the vital Qi can still resist exogenous pathogens, and the pathogenesis is characterized by pathogenic excess (such as dampness heat and blood stasis). However, as the disease progresses to the middle stage, the vital Qi cannot overcome the pathogenic factors, various pathological products are formed, and its pathogenesis characteristics change into a mixture of deficiency and excess. When the disease progresses to the terminal stage, the vital Qi is exhausted, and the pathogenesis is characterized by a deficiency of vital Qi (leading to the accumulation of liquid and turbid toxin). In different stages of nephropathy, the priority of the deficiency and the excess are different. Deficiency and excess are cause and effect of each other, which leads to the continuous progress of CKD. (B) Cognition and treatment strategy of CKD in the TCM theory. On the left are the modern medical characteristics and the main pathological process of CKD. On the right is the treatment strategy of TCM using CMM, and the representative CMMs corresponding to each pathogenesis are listed.

FIGURE 2

Summary of the related mechanism of treating CKD with CMM. TGF-β/Smad and Wnt/β-catenin signaling pathways are two antifibrotic mechanisms that have been confirmed by a variety of TCM studies. Among them, Smad3 is pathogenic in renal fibrosis but Smad7 plays a protective role by negatively regulating the phosphorylation of Smad2/3 and NF-κB-driven inflammatory response. For the dual functions of Smad4, the therapeutic effect of CMM is to inhibit Smad3-dependent renal fibrosis. Besides, the sustained excessive reaction of abnormal activation of the PI3K/Akt/mTOR signaling pathway can lead to an increase in Col I and FN and ultimately lead to renal fibrosis. In the occurrence of glomerular hyperperfusion, hyperfiltration, and hyperglycemia, it causes oxidative stress and AGE activation, followed by a series of inflammatory reactions. In addition to inhibiting the activation of AGE, the antiinflammatory effect of CMM is also manifested in the inhibition of ROS-ERK1/2 and NF-κB-mediated NLRP3 inflammasomes.