**2. Kidney stores essence theory**

#### **2.1. Kidney stores essence (Jing)**

Essence (Jing) is the basic substance both constituting the body and supporting its func‐ tional activities. The functions of essence are controlling reproduction, growth, and devel‐ opment, promoting the transformation of blood. For example, the forward movement of sperm in infertile men with kidney deficiency was much lower than that in fertile men, and the expression of c‐kit mRNA, a marker of sperm damage, was increased [14]. For female, more than half of premature ovarian failure (POF) patients were differentially diagnosed by TCM as deficiency of kidney in 122 cases [15]. Destruction of the gonad was usually used to induce kidney deficiency animal model. Kidney‐essence deficiency mice showed lower sperm density and motility, and lesser number of baby mice. The same is true for their descendants [16].

According to Suwen (Plain Questions), a classical work of the TCM theory, kidney essence controls the natural human processes from birth to death. There is an abundance of kid‐ ney essence in childhood, which provides the power to grow teeth, hair, and bones. During puberty, the kidney essence is even more plentiful resulting in the ability of fertility. Then female fertility begins to decline after 35 years old and male's after 40, as the kidney essence starts to decline. In old age, the kidney essence depletes as time passes, accompanying with infertility, osteoporosis, anemia, baldness, tinnitus, and even hearing loss. Therefore, aging is considered to be physiological kidney deficiency [17].

#### **2.2. Kidney rules water**

As urinary organs, TCM kidney and anatomical kidneys both bear consistency of functional. In the rat model of kidney‐yang deficiency, classical kidney‐nourishing formulas strongly regulated the RAA system hormone disorder [18].

#### **2.3. Kidney governs reception of qi**

According to the TCM theory, kidney controls deep and normal breathing in spite of the dif‐ ficult‐to‐understand relationship between the kidneys and the lungs. It has been proved that kidney deficiency related closely with stable phase of chronic obstructive pulmonary disease (COPD) [19]. Geng et al. [20] found that the number of asthma attacks of children treated with tonifying qi and kidney TCM significantly decreased, and the effect remained after with‐ drawal of TCM for 9 months.

#### **2.4. Kidney controls the bones**

academic view. Moreover, chromosome [5], vitamin D (calcitriol) [6], and erythropoietin (EPO) [7] were also considered to be the material basis of kidney essence. In modern medi‐ cine, the kidneys are endocrine organs that secrete a variety of hormones, such as renin [8], kallikreins [9], EPO [10], calcitriol [11], BMP‐7 [12], and klotho [13]. This chapter aims to compare the similarities of the essence of kidney in TCM and the active substance secreting by the kidneys, and to propose the idea that renal endocrine function has the potential to be

14 Chinese Medical Therapies for Diabetes, Infertility, Silicosis and the Theoretical Basis

Essence (Jing) is the basic substance both constituting the body and supporting its func‐ tional activities. The functions of essence are controlling reproduction, growth, and devel‐ opment, promoting the transformation of blood. For example, the forward movement of sperm in infertile men with kidney deficiency was much lower than that in fertile men, and the expression of c‐kit mRNA, a marker of sperm damage, was increased [14]. For female, more than half of premature ovarian failure (POF) patients were differentially diagnosed by TCM as deficiency of kidney in 122 cases [15]. Destruction of the gonad was usually used to induce kidney deficiency animal model. Kidney‐essence deficiency mice showed lower sperm density and motility, and lesser number of baby mice. The same is true for their

According to Suwen (Plain Questions), a classical work of the TCM theory, kidney essence controls the natural human processes from birth to death. There is an abundance of kid‐ ney essence in childhood, which provides the power to grow teeth, hair, and bones. During puberty, the kidney essence is even more plentiful resulting in the ability of fertility. Then female fertility begins to decline after 35 years old and male's after 40, as the kidney essence starts to decline. In old age, the kidney essence depletes as time passes, accompanying with infertility, osteoporosis, anemia, baldness, tinnitus, and even hearing loss. Therefore, aging is

As urinary organs, TCM kidney and anatomical kidneys both bear consistency of functional. In the rat model of kidney‐yang deficiency, classical kidney‐nourishing formulas strongly

According to the TCM theory, kidney controls deep and normal breathing in spite of the dif‐ ficult‐to‐understand relationship between the kidneys and the lungs. It has been proved that kidney deficiency related closely with stable phase of chronic obstructive pulmonary disease (COPD) [19]. Geng et al. [20] found that the number of asthma attacks of children treated

one of the kidney essence.

descendants [16].

**2.2. Kidney rules water**

**2. Kidney stores essence theory**

considered to be physiological kidney deficiency [17].

regulated the RAA system hormone disorder [18].

**2.3. Kidney governs reception of qi**

**2.1. Kidney stores essence (Jing)**

Stored in the kidneys, essence can transform into the marrow that fills up the bone cavities, where the blood is produced. The brain is even named as the "sea of marrow." For this reason, kidney essence is so important for bone development, healthy teeth, blood formation, and normal cognitive function. For example, the risk of fracture is significantly higher in chronic kidney disease (CKD) patients than in the general population [21]. The expenditures of oral problems also increased steadily along with the severity of CKD stages [22]. Homeostasis of calcium and phosphate maintain the development of bones. Many renal endocrines take part in the courses of bone metabolism, such as 1, 25(OH)2 D3 , Klotho, BMP‐7, and EPO. Aging may increase the risk of kidney dysfunction, and finally results in cardiovascular events, metabolic bone diseases, and even death [23].

When people are getting old, cognitive problems become more and more evident, such as amnesia, retard response, apathy, agnosia, and depression. The disorder of memory and cog‐ nitive deficit are usually related to Alzheimer's disease (AD) and vascular dementia (VD). TCM considered that the elderly person initially with kidney deficiency tends to have demen‐ tia. Promoting the transformation of blood is another function of kidney essence. Therapy of nourishing kidney [24] could promote the proliferation and differentiation of bone marrow hematopoietic progenitor cells *in vitro*.

#### **2.5. The kidney influences the hair luster**

Hair is nourished by the blood, which is generated from essence. Hairs collected from kidney deficiency patients [25] showed the shortest hair diameter and the relatively wide intervals between cuticles. Meanwhile, the levels of trace elements [26] and amino acids [27] in hair of patients with renal diseases decreased.

#### **2.6. Ears as window of kidney**

Presbycusis is regarded as a model of "kidney deficiency" deafness in TCM. The GC/MS analysis showed that hearing loss in the elderly people were positively correlated with kid‐ ney deficiency score in TCM [28]. It may be related to glutathione metabolism, amino acid metabolism, glucose metabolism, NMDA receptors, and GABA receptors. In addition, the ear length declined with the diminished kidney function after kidney donation [29].

In summary, the Five‐Element theory serves to categorize all things in nature with the char‐ acteristics of five elements (**Figure 1**). Meridian tropism is used to explain the selectivity of drug action on a part of the body. For example, TCM considered that "salty flavor entering the kidney," "black food nourishing the kidney," and "correspondence of kidney with win‐ ter." Modern research has shown that salt is associated with the secretion of renin and the occurrence of high blood pressure. Black rice rich in several anthocyanins are effective in the prevention of hypertension [30].

**Figure 1.** Categorization of kidney manifestation.

## **3. Renal endocrine and the "kidney stores essence" theory**

According to the similarities of the kidney endocrine substances and the kidney essence in the sources and functions (**Figure 2**), we summarize several hormones secreted by the kidneys.

Renin is produced by renal juxtaglomerular epithelioid cells [8], and its secretion is with salt sensitivity [31]. Renin is believed as the regulators of kidney‐yang, due to its partici‐ pation in the blood pressure control system. In contrast, kallikrein‐kinin system (KKS), mainly expressed in the distal tubules and collecting ducts of kidney [9], can lower blood pressure and promote the differentiation of stem cells, as the regulator of kidney‐yin. Unlike the two above, EPO is exclusively secreted by renal interstitial fibroblast cells [10], which can regulate differentiation of red blood cells, stem cells, and progenitor cells. It is a veritable substance of nourishing blood. Calcitriol and BMP‐7 are the presentations of the "kidney controls the bones" theory. The former is produced via 25‐hydroxyvitamin D3 1 alpha‐hydroxylase (CYP27B1) in renal proximal tubular cells [11], while the latter is expressed in the renal outer medulla and in glomeruli, and in several glomerular cell types, such as mesangial, epithelial, and endothelial cells [12]. Knocking out BMP‐7 in mice resulted in death shortly after delivery, with kidney failure, skeleton deformity, and eye loss [32].

As one of the material basis of the "kidney stores essence" theory, we will highlight α‐klotho in this chapter. Klotho is mainly expressed in the distal tubule and the collecting duct [13]. As a longevity gene klotho has been widely known, as its reduction directly affects life expectancy [33]. Compared with the wild‐type littermates, serum klotho level is reduced by approximately 80% in mice with renal‐specific deletion of klotho, and exhibited severe growth retardation, kyphosis, and premature death. Serum α‐klotho levels in healthy people rise with age to young adults and then gradually decline while age increased, showing a parabola [34]. The change of α‐klotho level (**Figure 3**) is consistent with the description of kidney essence in Suwen.

The Connotation of Kidney Stores Essence Theory and Kidney Endocrine Substance http://dx.doi.org/10.5772/66972 17

**Figure 2.** Similarity of kidney endocrine substances and kidney essence.

**3. Renal endocrine and the "kidney stores essence" theory**

16 Chinese Medical Therapies for Diabetes, Infertility, Silicosis and the Theoretical Basis

**Figure 1.** Categorization of kidney manifestation.

D3

eye loss [32].

kidney essence in Suwen.

According to the similarities of the kidney endocrine substances and the kidney essence in the sources and functions (**Figure 2**), we summarize several hormones secreted by the kidneys.

Renin is produced by renal juxtaglomerular epithelioid cells [8], and its secretion is with salt sensitivity [31]. Renin is believed as the regulators of kidney‐yang, due to its partici‐ pation in the blood pressure control system. In contrast, kallikrein‐kinin system (KKS), mainly expressed in the distal tubules and collecting ducts of kidney [9], can lower blood pressure and promote the differentiation of stem cells, as the regulator of kidney‐yin. Unlike the two above, EPO is exclusively secreted by renal interstitial fibroblast cells [10], which can regulate differentiation of red blood cells, stem cells, and progenitor cells. It is a veritable substance of nourishing blood. Calcitriol and BMP‐7 are the presentations of the "kidney controls the bones" theory. The former is produced via 25‐hydroxyvitamin

 1 alpha‐hydroxylase (CYP27B1) in renal proximal tubular cells [11], while the latter is expressed in the renal outer medulla and in glomeruli, and in several glomerular cell types, such as mesangial, epithelial, and endothelial cells [12]. Knocking out BMP‐7 in mice resulted in death shortly after delivery, with kidney failure, skeleton deformity, and

As one of the material basis of the "kidney stores essence" theory, we will highlight α‐klotho in this chapter. Klotho is mainly expressed in the distal tubule and the collecting duct [13]. As a longevity gene klotho has been widely known, as its reduction directly affects life expectancy [33]. Compared with the wild‐type littermates, serum klotho level is reduced by approximately 80% in mice with renal‐specific deletion of klotho, and exhibited severe growth retardation, kyphosis, and premature death. Serum α‐klotho levels in healthy people rise with age to young adults and then gradually decline while age increased, showing a parabola [34]. The change of α‐klotho level (**Figure 3**) is consistent with the description of

**Figure 3.** (A) Changes of kidney essence with age according to description of "Suwen." (B) Serum level of klotho protein changes with the human age [34].

Many studies have shown that α‐klotho deficiency affects bone marrow stem cells and blood cell growth, development, and differentiation [35–37]. α‐Klotho and EPO can be regulated by each other [38, 39]. Obviously, the role of α‐klotho is very similar to the TCM theory of "kid‐ neys essence generating marrow and producing blood."

Modern medical research has elucidated that α‐klotho deficiency causes bone matrix protein distribution changes and calcification defect [40]; and participates in calcium and phosphorus metabolism [41]. α‐Klotho also regulates the expression of vitamin D receptor [42]. It is clear that the lack of 1,25‐dihydroxyvitamin D3 can lead to osteoporosis [43]. Studies have shown that the introduction of variant KL‐VS of the human KLOTHO gene in mice enhances cogni‐ tive function and increases serum α‐klotho levels [44].

It has also been observed that there is a relationship between klotho and reproductive func‐ tion [39]. The Nabeshima group also found that klotho‐deficient mice have abnormal regula‐ tion of gonadotropins [45]. Recent studies have shown that maternal serum α‐klotho exhibits positive association with fetal birth weight [46]. Our research shows that klotho expression in testis in 30‐week‐old SHR is significantly lower than that of normal controls Wistar‐Kyoto (WKY) rats [47]. At present, although there is no direct evidence to prove the relationship between angiotensin II and klotho in testes, a lot of circumstantial evidence appears that klotho protect the organs and antagonistic effects of angiotensin II [48, 49]. Overall, we find that klotho function and the "kidney stores essence" theory have many overlapping and cov‐ ering, reflecting the similarities between the two.
