Clinical Effects Of Traditional Chinese Medicine in Delaying The Progression Of Chronic Renal Failure

2 Clinical effects of traditional Chinese medicine in delaying the progression of chronic renal failure

Clinically, there are two main stages of renal dysfunction in patients with CRF. The early stage of mild renal function decline is equivalent to CKD stage 3, that is, the glomerular filtration rate (GFR) drops to 30-59 mL/(min·1.73 m2). At this stage, patients often have no obvious clinical symptoms, but only slightly increased serum creatinine (Scr) and serum urea nitrogen (BUN). Some patients may be accompanied by increased nocturia and mental fatigue. Symptoms such as strength, backache and knee weakness. Clinical practice shows that at this stage, traditional Chinese medicine can directly improve glomerular filtration function and delay the progression of CRF. Another stage is the stage of moderate to severe decline in renal function, which is equivalent to CKD stages 4 and 5.

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Due to the accumulation of various nitrogen metabolism toxins in the patient's body and the disturbance of water, electrolyte, and acid-base balance, the clinical manifestations of functional damage to various organs and systems of the body appear. At this stage, the role of traditional Chinese medicine is mainly reflected in the improvement of complications such as "gastrointestinal tract, cardiovascular, calcium/phosphorus metabolism, malnutrition, endocrine abnormalities, and low immunity" in CRF patients. As for toxins to uremia, except for traditional organic small molecular substances, such as BUN, Scr, uric acid (UA), guanidine, etc., traditional Chinese medicine also has a certain clearance for "middle molecular substances and hormone macromolecular substances" effect.

 2.1 The effect of traditional Chinese medicine on renal function

Japanese scholar Mizuma Zhongdao applied Wenpi Decoction (rhubarb, aconite, dried ginger, ginseng, licorice) to treat 8 CRF azotemia patients and did a 5-year outpatient follow-up. Among them, 5 patients received the whole course of treatment. Wenpi Decoction was prescribed as a single prescription for ( 207. 0 ± 110. 5) weeks, during which the patient continued to receive the original antihypertensive drugs, diuretics, and antiplatelet aggregation drugs, blood uric acid-lowering drugs, and electrolyte-improving drugs. Observation items include Scr, BUN, UA, serum potassium (K+), serum calcium (Ca2+), serum phosphorus (P3+) and so on. The author used the traditional Mitch method to calculate 1/Scr to judge the rate of renal damage, and the endpoint was Scr 880.4 μmol·L -1. 

The results showed that Wenpi Decoction improved 1/Scr, the time of entering dialysis in CRF patients was prolonged to ( 262. 0 ± 145. 8) weeks, and Scr increased from ( 397. 8 ± 212. 16 ) μmol·L - 1 before treatment To ( 742. 56 ± 318. 24 ) μmol·L - 1 , BUN increased from ( 13. 57 ± 4. 11) mol · L - 1 to ( 31. 09 ± 10. 89) mmol · L - 1 before treatment 1. Blood P3 + increased from (1. 39 ± 0. 25) mmol·L - 1 to ( 1. 71 ± 0. 35) mmol · L - 1 before treatment, while blood

K + , blood Ca2 + , UA did not change significantly. The authors believe that long-term use of Wenpi Decoction can delay the progression of CRF patients into end-stage renal disease [37].

Guo Zhaoan et al. randomly divided 194 CRF patients with Scr between 177 and 707 μmol·L - 1 into a treatment group (128 cases) and a control group (66 cases). The patients in the treatment group were treated with nitrogen-clearing enema solution (rhubarb, dandelion, raw peony, cooked aconite, salvia, etc.), and the patients in the control group were treated with aldehyde-oxidized starch.

The author observed the symptoms, signs, and renal function-related indexes of the two groups of patients before and after treatment, and also focused on the comparison of serum middle molecular substance (MMS), parathyroid hormone (PTH), blood Ca2+, blood Changes in indicators such as P3+. The results showed that in the treatment group, 74 cases were markedly effective, 38 were effective, 16 were ineffective, with a total effective rate of 87.5%; in the control group, 18 were markedly effective, 26 were effective, and 22 were ineffective, with a total effective rate of 66.5%. 7%; the difference in the total effective rate between the two groups was very significant (P ＜ 0.01); after the treatment with the nitrogen-clearing enema, the symptom and sign scores of the patients in the treatment group decreased, and compared with the control group, the difference was significant ( P ＜ 0. 05), and the blood MMS, PTH, Ca2 + , P3 + were all lower than those before treatment (P ＜ 0. 05 or P ＜ 0. 01), compared with the control group, the difference was significant (P < 0.05).

The authors believe that for non-dialysis patients with CRF, a nitrogen-clearing enema can improve renal function and regulate calcium/phosphorus metabolism disorders [34]. Studies have shown that the clinical indicators that can reflect early renal dysfunction are also serum cystatin protease inhibitors [referred to as cystatin C (CysC)] [38]. Domestic scholars Dong et al. observed 68 cases of CRF patients with renal function compensation stage (equivalent to CKD stage 2). The patients were randomly divided into a treatment group and a control group with 34 cases in each. The patients in the control group were given basic treatment with a low-protein and low-phosphorus diet, while those in the treatment group were given Guben Qudu Yishen Decoction (Sheng Astragalus, Cistanche deserticola, Eucommia ulmoides, Chinese yam, Poria, Polyporus, Alisma, Danshen, Ji Snow grass, June snow, rhubarb, dogwood, etc.) orally.

During 48 months, CysC, Scr, BUN, and GFR of 2 groups of patients were observed every 3 months. The authors found that the CysC, Scr, and BUN of the control group did not change significantly before and after treatment, and the GFR decreased from ( 66. 86 ± 6. 43) mL·min - 1 to ( 42. 34 ± 3. 28) mL before treatment ·min - 1, while the patients in the treatment group received Guben Qudu Yishen Decoction combined with a low-protein diet and low-phosphorus treatment for 48 months, their CysC, Scr, and BUN all showed a downward trend, especially CysC, Scr improved most obviously, CysC From before treatment ( 3. 85 ± 1. 23 ) g · L - 1 to ( 2. 13 ± 0. 83) g · L - 1, Scr decreased from before treatment ( 135. 28 ± 39. 88) μmol · L -1 decreased to ( 95.26 ± 14.69) μmol·L -1. Therefore, the authors believe that for CKD2 patients with renal function compensation, the change rule of CysC is the same as that of Scr, which can reflect the excessive function of the glomerulus; Guben Qudu Yishen Decoction combined with low-protein and low-phosphorus diet can delay early CRF. Decreased glomerular filtration function in patients [39].

Recent studies have shown that colon dialysis combined with traditional Chinese medicine-Cistanche retention enema is an important method to improve the efficacy of traditional Chinese medicine in the treatment of CRF.

There were 72 non-dialysis CRF patients (equivalent to CKD stage 3 to 5), 36 in the treatment group and 36 in the control group.

The patients in the two groups were treated with colon dialysis combined with traditional Chinese medicine retention enema or traditional Chinese medicine retention enema alone while receiving basic treatment (including correction of water, electrolyte, acid-base balance disorders, improvement of anemia, and low-quality protein diet, etc.). The patients in the treatment group first received whole colon cleansing, and then colon dialysis for 40 min. After the dialysis, they were given Jiedu Xiezhuo No. Ⅱ traditional Chinese medicine solution (raw rhubarb, calcined keel, calcined oyster, sophora japonica, Junexue, tuckahoe, whole Scorpion, Dilong, etc.) retention enema (2 to 3 h); patients in the control group only received retention enema with the same traditional Chinese medicine solution. The course of treatment is 2 weeks.

The authors compared the changes of TCM syndromes, BUN, Scr, creatinine clearance rate (Ccr), UA between the two groups of patients before and after treatment. The results showed that the total effective rate of the treatment group was 88.9%, which was significantly better than that of the control group (69.4%) (P < 0.05). The authors believe that colon dialysis can excrete urine toxins in the large intestine by means of the exchange and absorption of dialysate in the intestinal lumen. The liquid directly reaches the descending colon, which not only expands the contact area between the intestinal mucosa and the traditional Chinese medicine, but also keeps the traditional Chinese medicine in the intestinal cavity for a long time, thereby increasing the absorption of the traditional Chinese medicine. Therefore, colon

It has been analyzed that the combination of traditional Chinese medicine retention enema can improve the efficacy of traditional Chinese medicine in the treatment of CRF [40]. 

2.2 The effect of traditional Chinese medicine on the complications of uremia

Clinical practice shows that Chinese medicine has a certain improvement effect on skin itching and muscle spasm associated with hemodialysis in patients with advanced CRF (uremia). Itchy skin is a common symptom in patients with uremia, and its mechanism may be related to histamine release or calcium/phosphorus metabolism disturbance. Huang Xiaoqin et al used auricular acupuncture plus traditional Chinese medicine medicated bath to treat itchy skin in CRF patients. The authors randomly divided 104 uremia patients with itchy skin into the routine group, medicated bath group, and acupuncture plus medicated bath group. , wild chrysanthemum, etc.), acupuncture (ear points such as the liver, spleen, endocrine, adrenal gland, diaphragm, Shenmen, Fengxi, etc.) plus medicated bath therapy. The results showed that the degree of pruritus in both the medicated bathing group and the acupuncture plus medicated bathing group was alleviated after treatment, and there was a significant difference in the clinical scores between the groups (P ＜ 0. 05 or P ＜ 0. 01). The effect of acupuncture plus medicated bath group was significantly better than that of medicated bath group and routine group ( P ＜ 0. 01 ). The authors believe that auricular acupuncture plus traditional Chinese medicine bath has a good effect on skin itching in patients with uremia [41]. Hinoshita et al selected 5 patients with severe muscle spasms on maintenance hemodialysis and treated them with shakuyaku-kanzo-to granules (6 g per day) for 4 weeks. The authors found that muscle spasms basically disappeared in 2 patients, and the frequency of muscle spasms in the other 3 patients was significantly lower than that before treatment, and the degree was also obvious. alleviated, and, during the treatment period, there were no adverse drug reactions. Therefore, the authors believe that Shaoyao Gancao Decoction can effectively prevent and treat muscle spasms in hemodialysis patients [42].

To sum up, the mechanism of Chinese medicine delaying the progression of CRF mainly refers to the effect of Chinese medicine on improving glomerular sclerosis and renal interstitial fibrosis, for example, by affecting glomerular hemodynamics, reducing podocyte damage, and inhibiting TGF-β expression. , adjust lipid metabolism disorder to improve glomerular sclerosis; improve renal interstitial fibrosis by reducing macrophage infiltration, inhibiting renal tubular epithelial cell transdifferentiation, and reducing urinary protein toxicity. The clinical effects of traditional Chinese medicine in delaying the progression of CRF are mainly reflected in the improvement of renal function and certain complications. In addition, Chinese medicine also has a certain improvement effect on calcium/phosphorus metabolism imbalance, micro-inflammatory state, and uremic toxin accumulation in patients with advanced CRF. Japanese scholars also found that Cistanche can replace hormones to treat peritoneal fibrosis (retroperitoneal fibrosis, RF) in CRF patients undergoing peritoneal dialysis [43].

The author believes that the azotemia stage is a relatively stable disease stage during the progression of CRF, which generally lasts for more than 5 to 10 years. At this stage, the patient has not yet developed a severe multi-system disease, and the clinical features are relatively clear. Therefore, the azotemia stage is the best stage to clarify the clinical effect of traditional Chinese medicine in delaying the progression of CRF. Domestic scholars should collect large samples of clinical data as possible to reveal the laws of TCM syndromes and select relatively uniform treatment plans and drugs to clarify the real effects of TCM in improving renal function indicators. As for the study of the pharmacological mechanism, it is still necessary to focus on glomerulosclerosis and renal interstitial fibrosis. Therefore, it is very important to establish a living model of progressive glomerulosclerosis with renal dysfunction. Although the 5/6 nephrectomy model lacks immune-mediated inflammatory responses, there is also no reliable non-invasive means to detect hyperfiltration in surviving nephrons in the living model, however, this model has typical glomerulosclerosis, Therefore, it has been recognized by scholars at home and abroad.

In addition, another progressive glomerulosclerosis model was developed by the Institute of Nephrology, Niigata University, Japan [44]. Munich Wistar mice first received unilateral nephrectomy, and then, a one-time injection of an anti-Thy-1.1 monoclonal antibody, the model mice developed progressive glomerulosclerosis and renal insufficiency in the 2nd week after modeling; in the 7th week, The 24-hour urinary protein excretion and BUN of the model mice increased to 229.3 mg and 2 171 mg·L - 1, respectively. Among them, glomerular hemodynamics disturbance (glomerular hemodynamics turbulence) is the fundamental factor causing the progression of glomerular sclerosis in model mice. The author believes that with the help of this model, the effect and mechanism of traditional Chinese medicine in delaying the progression of CRF can be directly elucidated in vivo.

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