How Cistanche Help With Reducing Or Slowing There Rate Of Ckd
Mar 20, 2023
Objective
To observe the changes of serum fibroblast growth factor 23 (FGF23), fibroblast growth factor receptors (FGFRs), Klotho protein levels and the intervention effect of Cistanche, Rhizoma, Radix et Rhizoma granules in patients with abnormal kidney deficiency and damp-heat evidence of non-dialysis chronic kidney disease mineral and bone metabolism (CKD-MBD).
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Methods
Seventy patients with non-dialysis CKD-MBD with kidney deficiency and damp-heat evidence who met the inclusion criteria were randomly divided into 35 cases each in the treatment group and the control group, and finally 65 cases were actually completed, 33 cases in the control group and 32 cases in the treatment group, and 20 cases in the normal group. Patients in both groups were given conventional treatment and combined with Chinese medicine reserved enema, and the treatment group added Cistanches, Rhizoma, Radix et Rhizoma granules on top of this, which was taken with warm water, 3 times/d, 1 bag/time. The duration of treatment was 12 weeks in both groups. The changes of TCM symptoms in both groups were observed and recorded, and serum calcium (Ca), phosphorus (P), parathyroid hormone (iPTH), FGF23, FGFRs and Klotho protein were detected before and after treatment in both groups, while serum FGF23, FGFRs and Klotho protein levels in the normal group were detected.
Results
The efficacy of CKD-MBD was significantly better in the treatment group than in the control group after treatment (P < 0.05). In the treatment group, the CKD-MBD values at each time point were significantly lower than those before treatment (P < 0.05 or P < 0.01); in the control group, the CKD-MBD values at the end of the 12th week of treatment only were lower than those before treatment (P < 0.05); all the treatment groups were significantly better than the control group (P < 0.01). Serum Ca, P, and iPTH improved in the treatment group at all time points after treatment compared with pre-treatment (P < 0.05 or P < 0.01). In the control group, serum Ca increased and serum P and iPTH decreased only at the end of treatment 12 week (P < 0.05). Before treatment, serum FGF23, FGFRs, and Klotho protein levels were statistically significant in the control and treatment groups compared with the normal group (P < 0.01). After treatment, serum FGF23, FGFRs, and Klotho protein levels in the treatment group were significantly improved compared with those before treatment (P < 0.05); serum FGF23, FGFRs, and Klotho protein levels in the control group were not significantly different compared with those before treatment (P > 0.05); all the treatment groups were superior to the control group (P < 0.05).
Conclusion
Cistanches, Rhizoma, Radix et Rhizoma granules can significantly improve the clinical symptoms of non-dialysis CKD-MBD patients with kidney deficiency and damp heat evidence, correct the calcium and phosphorus metabolism disorders in non-dialysis CKD-MBD patients with kidney deficiency and damp heat evidence, and inhibit secondary hyperparathyroidism, thus effectively preventing and treating CKD-MBD. The main mechanism of action may be related to the significant improvement of serum FGF23, FGFRs and Klotho protein levels.
Keywords: Abnormalities of mineral and bone metabolism in chronic kidney disease, Cistanche, Rhizoma, Radix et Rhizoma Granules, Kidney deficiency and damp heat, Fibroblast growth factor 23, Fibroblast growth factor receptor, Klotho protein
The epidemiology, pathogenesis and clinical management of chronic kidney disease (CKD) are hot topics of research for scholars at home and abroad today. Studies have shown [1-2] that the prevalence of CKD in China reached 10.8% in 2012, among which the number of patients with complications of chronic kidney disease mineral and bone metabolism abnormalities (CKD-MBD) was as high as 55.6%, which is one of the common serious complications of CKD patients and has seriously affected the survival quality of CKD patients. At present, modern medicine mainly uses diet control, oral phosphorus binding agents and active vitamin D preparations, and removal of parathyroid glands as the main means of treatment for CKD-MBD, but none of them has achieved satisfactory clinical results. Therefore, there are drawbacks in the treatment of CKD-MBD by Western medicine alone [3]. Chinese medicine has significant advantages in the treatment of CKD-MBD, which can not only correct the disorder of calcium and phosphorus metabolism, but also significantly improve the clinical symptoms and signs of patients and further delay the progression of the disease. Cistanches, Rhizoma, Radix et Rhizoma granules, an in-house preparation, is used to treat non-dialysis CKD-MBD patients with kidney deficiency and damp-heat symptoms, which can benefit the kidneys and detoxify the toxins, resolve blood stasis and release turbidity. Previous studies [4-6] showed that Cistanches, Rhizoma, Radix et Rhizoma granules could reduce serum osteoprotegerin (OPG) and nuclear factor-κB receptor activator ligand (RANKL) levels and increase serum bone morphogenetic protein-7 (BMP-7) and 1, 25 (OH)2D3 levels, thus improving renal function and clinical symptoms in patients with CKD-MBD, but the exact mechanism of this study is not clear. The present study is a prospective study (ethics committee of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, ethics number 2015AH-33), in which the effects of Cistanches, Rhizoma, Radix et Rhizoma granules on serum fibroblast growth factor 23 (FGF23), fibroblast growth factor receptors (FGFRs) and Klotho protein in non-dialysis CKD-MBD patients were observed. The effects of FGF23, FGFRs and Klotho proteins on serum fibroblast growth factor 23 (FGF23), fibroblast growth factor receptors (FGFRs) and Klotho proteins in patients with fever were investigated from the perspective of the FGF23-Klotho axis.
1. Information and methods
1.1. Western medical diagnostic criteria
1.1.1 Diagnostic criteria for CKD [7] (1) Renal damage (abnormal kidney structure or function) ≥ 3 months, with or without a decrease in glomerular filtration rate (GFR). One of the following may be present: abnormal pathology; or positive indicators of kidney damage: abnormal blood or urine composition or abnormal imaging; (2) GFR < 60 mL/(min-1.73 m2) ≥ 3 months, with or without evidence of kidney damage.
1.1.2 CKD staging criteria Stage 1: renal injury, normal or elevated GFR: GFR ≥ 90 mL/(min-1.73 m2); Stage 2: mild decrease in GFR: GFR in 60~89 mL/(min-1.73 m2); Stage 3a: mild to moderate decrease in GFR: GFR in 45~59 mL/(min-1.73 m2); Stage 3b Stage 4: moderate to severe decline in GFR: GFR in the range of 30-44 mL/(min-1.73 m2); Stage 4: severe decline in GFR: GFR in the range of 15-29 mL/(min-1.73 m2); Stage 5: renal failure: GFR < 15 mL/(min-1.73 m2) or dialysis.
1.1.3. Diagnostic criteria for CKD-MBD
Referring to the "Guidelines for the diagnosis and treatment of mineral and bone abnormalities in chronic kidney disease" issued by the Chinese Society of Nephrology in 2013 [8] formulated: (1) abnormalities in serum calcium (Ca), phosphorus (P), parathyroid hormone (iPTH) or vitamin D metabolism; (2) abnormalities in bone transformation, mineralization, bone volume, linear bone growth or bone strength; (3) vascular or other soft tissue calcification. CKD-MBD can be diagnosed if one of the above three points is met.
1.2. Diagnostic criteria of Chinese medicine evidence
The diagnostic criteria for kidney deficiency and damp-heat symptoms were formulated according to the "Guidelines for Clinical Research on New Chinese Medicines for Chronic Renal Failure" [9]. Secondary symptoms: weakness, abdominal fullness, bone pain, nausea, vomiting; tongue, moss, and pulse: red tongue with yellowish moss or yellowish thick, and moist pulse; diagnostic conditions: primary symptoms are required, secondary symptoms or both, combined with tongue and pulse.
1.3. Quantitative scoring criteria of TCM symptoms
Quantitative scoring criteria of TCM symptoms: Referring to the "quantitative scoring criteria of TCM symptoms" in the "clinical research guideline of new Chinese medicine for chronic renal failure" [9], 3, 6 and 9 points were recorded according to the mild, moderate and severe degree of the main symptoms and secondary symptoms, respectively, and 0 points were recorded if there were no corresponding clinical symptoms.
1.4. Case study criteria
1.4.1. Case inclusion criteria (1) Non-dialysis CKD-MBD patients with CKD stage 3-5 who meet the above diagnostic criteria of Western medicine and Chinese medicine; (2) Gradual increase in serum iPTH, with iPTH > 70 pg/mL in CKD stage 3 patients, > 110 pg/mL in CKD stage 4 patients, > 300 pg/mL in CKD stage 5 patients; (3) Gradual increase in serum iPTH, with iPTH > 300 pg/mL in CKD stage 5 patients; (4) Gradual increase in serum iPTH in CKD stage 3 patients, > 110 pg/mL in CKD stage 4 patients, > 300 pg/mL in CKD stage 5 patients. (3) Patients voluntarily participated in the clinical study and signed the informed consent form; (4) The age range was 18~50 years old.
1.4.2. Exclusion criteria (1) those who did not meet the inclusion criteria; (2) those who had undergone surgical resection of parathyroid glands; (3) those who had serious complications of primary diseases such as heart, brain and hematopoietic system; (4) female patients with perimenopause or menopause; (5) those with metabolic bone diseases such as osteoporosis and rickets caused by other causes; (6) those with serious complications such as hypertension, renal anemia, infection, acidosis, electrolyte disorders, etc. (7) patients who have entered renal replacement therapy and received immunosuppressive drugs within the last 6 months; (8) patients with infectious diseases such as hepatitis, syphilis, AIDS, autoimmune diseases, malignant tumors, etc.; (9) patients who are unable to cooperate, such as psychiatric patients.
1.5. Source of cases
All 70 cases in the clinical study were from outpatients and inpatients of the Department of Nephrology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, from January to October 2017, and non-dialysis CKD-MBD patients who met the above diagnostic criteria of Western medicine and the diagnostic criteria of Chinese medicine evidence.
1.6. Experimental grouping
The 70 patients with CKD-MBD who met the inclusion criteria were randomly divided into 35 cases in the control group and 35 cases in the treatment group, and the 70 patients were numbered into groups according to the random number table method. The actual completion was 65 cases, 33 cases in the control group and 32 cases in the treatment group. The gender, age, underlying disease and duration of CKD in the control group and treatment group were statistically treated, and there was no difference (P>0.05). The normal group consisted of 20 patients who were selected from the same period of health check-ups at our medical examination center, and their glomerular filtration rate (eGFR) was estimated to be ≥ 90 mL/(min-1.73 m2), and their serum FGF23, FGFRs and Klotho protein levels were measured.
1.7. Treatment
Both groups were given conventional treatment, including avoidance of drugs that may aggravate renal damage, hypotension, correction of renal anemia, and retention of enema with detoxifying and draining granules. In the treatment group, in addition to the control group, Cistanches, Rhizoma, Radix et Rhizoma granules (containing Cistanches, Rhizoma, Radix et Rhizoma, Niubizi, Dandelion, Junxue, Jiang Zhuru, Poria, Tao Ren, Glycyrrhiza glabra, made by the Pharmacy Department of Anhui Provincial Hospital of Traditional Chinese Medicine, 10 g per packet, product batch number: 20161211) were taken 3 times/d, 1 bag each time. The treatment course was 12 weeks.
1.8. observation indexes
1.8.1. Chinese medicine clinical performance Before treatment, at the end of 4 weeks of treatment, at the end of 8 weeks of treatment and at the end of 12 weeks of treatment, the changes of Chinese medicine clinical symptoms and signs were recorded once for non-dialysis CKD-MBD patients respectively, and the scores were recorded according to the quantitative symptom score.
1.8.2. renal function Before treatment, at the end of treatment 4, at the end of treatment 8 and at the end of treatment 12, serum Ca and P were measured by automatic biochemical analyzer, and eGFR was calculated by the simplified equation of EPI [10]; serum iPTH was measured by chemical immunoluminescence method; before treatment and at the end of treatment 12, serum FGF23 and FGFRs were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA). FGF23, FGFRs and Klotho protein were measured by ELISA before treatment and at the end of 12 weeks.
1.9. Criteria for determining the efficacy
At present, there is no unified standard for determining the efficacy of CKD-MBD at home and abroad, and this clinical study referred to the third edition of Nephrology [11(], edited by Wang Haiyan), the Guidelines for the diagnosis and treatment of mineral and bone abnormalities in chronic kidney disease issued by the Chinese Medical Association Nephrology Branch in 2013 [8] and the "Guidelines for clinical research on new Chinese medicines for chronic renal failure" in the "Guidelines for clinical research on new Chinese medicines for chronic renal failure" [9]. The efficacy of CKD-MBD was determined as follows: efficacy: reduction of clinical symptoms by 60% or more, and at least two of the serum Ca, P and iPTH were within the target range [12]. Effective: The clinical symptom score was reduced by 30%-60%, and only one of the serum Ca, P and iPTH was within the target range [12]. Ineffective: The clinical symptom score was reduced by 30% or less, and serum Ca, P, and iPTH were not within the target range [12].
1.10. Statistical methods
SPSS17.0 statistical software was used for analysis, and the mean ± standard deviation was used for measurement data; t-test was used for comparison between two groups and the data conformed to normal distribution; one-way ANOVA was used for comparison between two or more independent groups; the non-parametric test was used for data that did not conform to normal distribution; rank sum test was used for comparison between rank data; P < 0.05 was considered a statistically significant difference.
