Effectiveness of Chinese herbal medicine combined with Western medicine on deferring dialysis initiation for nondialysis chronic kidney disease stage 5 patients: a multicenter prospective nonrandomized controlled study.

BACKGROUND: In clinical practice, Chinese herbal medicine (CHM) purportedly has beneficial therapeutic effects for chronic kidney disease (CKD), which include delaying disease progression and dialysis initiation. However, there is a lack of high-quality evidence-based results to support this. Therefore, this study aimed to evaluate the efficacy of CHM combined with Western medicine in the treatment of stage 5 CKD. METHODS: This was a prospective nonrandomized controlled study. Stage 5 CKD (nondialysis) patients were recruited form 29 AAA class hospitals across China from July 2014 to April 2019. According to doctors' advice and the patients' wishes, patients were assigned to the CHM group (Western medicine + CHM) and the non-CHM group (Western medicine). Patient demographic data, primary disease, blood pressure, Chinese and Western medical drugs, clinical test results, and time of dialysis initiation were collected during follow-up. RESULTS: A total of 908 patients were recruited in this study, and 814 patients were finally included for further analysis, including 747 patients in the CHM group and 67 patients in the non-CHM group. 482 patients in the CHM group and 52 patients in the non-CHM group initiated dialysis. The median time of initiating dialysis was 9 (7.90, 10.10) and 3 (0.98,5.02) months in the CHM group and non-CHM group, respectively. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis [adjusted hazard ratio (aHR): 0.38; 95% confidence interval (CI): 0.28, 0.53] compared to those in the non-CHM group. After 1:2 matching, the outcomes of 160 patients were analyzed. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis (aHR: 0.32; 95% CI: 0.21, 0.48) compared to patients in the non-CHM group. Also, the Kaplan-Meier analysis demonstrated that the cumulative incidence of dialysis in the CHM group was significantly lower than that in the non-CHM group (log-rank test, P<0.001) before and after matching. CONCLUSIONS: This study suggest that the combination of CHM and Western medicine could effectively reduce the incidence of dialysis and delay the time of dialysis initiation in stage 5 CKD patients.

Efficacy and safety of Abelmoschus manihot for IgA nephropathy: A multicenter randomized clinical trial.

RATIONALE AND OBJECTIVE: IgA nephropathy (IgAN) is an important cause for end-stage renal disease worldwide. The treatment for IgAN remains challenging, and few randomized and controlled clinical trials have been conducted to evaluate new therapies. The present study assesses the efficacy and safety of Abelmoschus manihot (AM) in IgAN patients. STUDY DESIGN: Randomized, non-inferiority, double-blind, double-dummy multicenter trial. SETTING AND PARTICIPANTS: This trial was designed to recruit 1,600 biopsy-proven IgAN patients (proteinuria between 0.5-3.0 g/d and estimated glomerular filtration rate [eGFR] of ≥ 45 ml/min/1.73 m2) across China. INTERVENTIONS: The participants were randomized at 1:1 to AM (2.5 g for three times per day) or losartan potassium (100 mg per day) for 48 weeks. OUTCOMES: The primary outcome was the change in 24-hour proteinuria from baseline to week 48. The secondary outcomes were the change in eGFR from baseline to week 48, and the incidents of endpoint events (proteinuria ≥ 3.5 g/24 h, doubling of serum creatinine, or receiving renal replacement treatment). RESULTS: Among 1,470 randomized patients (mean age, 37.4 [SD, 10.6] years old; 777 [52.9%] were female; mean eGFR, 95.0 [SD, 24.3] mL/min/1.73 m2; mean 24-hour proteinuria, 1.2 [SD, 0.7] g/d), the mean decline in 24-h proteinuria at week 48 was 230 mg and 253 mg in the AM and losartan potassium groups, respectively (P = 0.676). The mean difference in the change in 24-h proteinuria between these two groups was -23.32 mg (95% confident interval: -123.2 to 76.6, p = 0.647). The mean decline in eGFR was 0.41 ml/min/1.73 m2 and 0.76 ml/min/1.73 m2 in the AM and losartan potassium groups, respectively (p = 0.661). The mean difference in the change in eGFR between these two groups was -0.43 ml/min/1.73 m2 (95% confident interval: -1.99 to 1.13, p = 0.589). The incidence of endpoint events was 8.6% in the AM group and 8.2% in the losartan group (p = 0.851). LIMITATIONS: The results of the trial may not be generalized to IgAN patients with a proteinuria of > 3.0 g/d and an eGFR of < 45 ml/min/1.73 m2. The long-term benefits of AM in reducing the risk of progressive renal dysfunction remains unclear, based on this 48-week observation. CONCLUSION: AM can be recommended as a promising treatment for IgAN patients.

Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study.

OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min-1•1.73 m-2, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) µmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min-1•1.73 m-2, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min-1•1.73 m-2 per year. CONCLUSION: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

Effects of adding Rheum officinale to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on renal function in patients with chronic renal failure: A meta-analysis of randomized controlled trials
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OBJECTIVE: Rheum officinale is a traditional medicinal herb used widely in China to treat chronic renal failure, but the proof of evidence-based medicine is poor. This meta-analysis aims to assess the benefits of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) supplemented with Rheum officinale for delaying the progression of chronic renal failure. MATERIALS AND METHODS: The MEDLINE, EMBASE, Cochrane Library, SinoMed, Chinese National Knowledge Infrastructure, Wanfang, and VIP databases were searched to identify studies published before September 2016 that investigated the effects of ACEI/ARB plus the Chinese patented medicine Rheum (CPM-Rheum) compared to ACEI/ARB alone in lowering serum creatinine (SCr) and blood urea nitrogen (BUN) levels in chronic renal failure patients. Review Manager 5.3 was used to perform the meta-analysis. Fixed- and random-effects models were used to analyze the data. RESULTS: The meta-analysis included nine clinical trials. Comparisons of patients before and after treatment with ACEI/ARB plus CPM-Rheum or ACEI/ARB alone revealed that ACEI/ARB plus CPM-Rheum resulted in significantly greater reductions in SCr (short-term: weighted mean difference (WMD): 17.26, 95% confidence interval (CI): 7.28 - 27.24; long-term: WMD: 63.71, 95% CI: 51.01 - 76.41) and BUN (short-term: WMD: 1.70, 95% CI: 1.27 - 2.12; long-term: WMD: 3.98, 95% CI: 3.14 - 4.82) than ACEI/ARB alone. CONCLUSION: In patients with chronic renal failure, the addition of CPM-Rheum to ACEI/ARB significantly lowered both SCr and BUN, particularly after long-term administration. Thus, the combination of ACEI/ARB and CPM-Rheum may improve the treatment of patients with impaired renal function.
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Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction: A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study.

BACKGROUND: Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. METHODS: The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min-1·1.73 m-2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. RESULTS: A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and the median change in eGFR was -0.2 (-4.3-2.7) and -2.2 (-5.7-0.8) ml·min-1·1.73 m-2, respectively (Z = -2.408, P = 0.016). There were no significant differences in adverse events between the groups. CONCLUSIONS: Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102.

Abelmoschus manihot - a traditional Chinese medicine versus losartan potassium for treating IgA nephropathy: study protocol for a randomized controlled trial.

BACKGROUND: IgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide, but effective therapy remains limited and many patients progress to end-stage renal disease (ESRD). Only angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin-receptor blockers (ARB) show a high level of evidence (1B level) of being of value in the treatment for IgAN according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. However, traditional Chinese medicine has raised attention in kidney disease research. Abelmoschus manihot, a single medicament of traditional Chinese medicine has shown therapeutic effects in primary glomerular disease according to the randomized controlled clinical trial that we have completed. Here, we conduct a new study to assess the efficacy and safety of Abelmoschus manihot in IgAN. Also, this study is currently the largest double-blind, randomized controlled registered clinical research for the treatment of IgAN. METHODS: We will conduct a multicenter, prospective, double-blind, double-dummy randomized controlled study. The study is designed as a noninferiority clinical trial. Approximately 1600 biopsy-proven IgAN patients will be enrolled at 100 centers in China and followed up for as long as 48 weeks. IgAN patients will be randomized assigned to the Abelmoschus manihot group (in the form of a huangkui capsule, 2.5 g, three times per day) and the losartan potassium group (losartan potassium, 100 mg/d). The primary outcome is the change in 24-h proteinuria from baseline after 48 weeks of treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after 48 weeks of treatment, the incidence of endpoint events (proteinuria ≥3.5 g/24 h, the doubling of serum creatinine, or receiving blood purification treatment) are the secondary outcomes. Twenty-four-hour proteinuria and eGFR are measured at 0, 4, 12, 24, 36 and 48 weeks. DISCUSSION: This study will be of sufficient size and scope to evaluate the efficacy and safety of Abelmoschus manihot compared to losartan potassium in treating patients with IgAN. The results of this study may provide a new, effective and safe treatment strategy for IgAN. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02231125 . Registered on 30 August 2014.

Safety and efficiency of microwave ablation for recurrent and persistent secondary hyperparathyroidism after parathyroidectomy: A retrospective pilot study.

BACKGROUND: Recurrent and persistent secondary hyperparathyroidism (SHPT) nodules have an incidence of 10-70% after surgery. The treatment of recurrent and persistent SHPT nodules is a challenge, and surgical resection of difficult-to-reach or post-operative adhesions often fails. PURPOSE: The aim of this research was to study the safety and effectiveness of microwave ablation (MWA) for recurrent and persistent SHPT. MATERIALS AND METHODS: This was a retrospective study of 11 patients enrolled with a total of 16 nodules, and MWA was employed to manage SHPT. The laboratory test results, including the intact parathyroid hormone (iPTH), serum calcium, phosphorus and alkaline phosphatase (ALP) levels, improvement of SHPT-related symptoms after ablation, and complications during and after MWA were recorded and analysed. RESULTS: After ablation the value of iPTH was markedly decreased from 1570 ± 1765 pg/mL to 287 ± 239 pg/mL 1 day after MWA (p < 0.05). The levels of serum calcium and phosphorus decreased from 2.51 ± 0.23 mmol/L to 2.06 ± 0.27 mmol/L (p < 0.001) and 1.80 ± 0.43 mmol/L to 1.48 ± 0.32 mmol/L (p < 0.05), respectively, 1 day after MWA. There was no significant difference in the ALP value before and after MWA (p > 0.05). The clinical symptoms, including ostalgia, pruritus, disability, and restless legs, improved after MWA. Minor complications and side effects encountered during or after MWA include haematoma (1/11, 9%), transient hoarseness (2/11, 18.2%), hypocalcemia (6/11, 54.5%). No major complication occurred. CONCLUSION: MWA may be safe and effective to manage recurrent and persistent SHPT nodules; a definite conclusion needs to expand the sample size with a longer follow-up time.

[Total parathyroidectomy in treatment of Sagliker syndrome in 10 cases of hemodialysing patients with secondary hyperparathyroidism].

OBJECTIVE: To evaluate the efficacy of the parathyroidectomy (PTX) in the treatment of severe secondary hyperparathyroidism (SHPT) with Sagliker syndrome (SS). METHODS: A retrospective review was undertaken among 212 SS patients underwent PTX in our hospital and with more than 3 years' follow up. The definitions of the efficacy were based on the postoperative intact parathyroid hormone level (iPTH). "Cure" showed that the iPTH was < 150 ng/L; "marked effectiveness" was 150 - 300 ng/L; "effectiveness" was 301 - 500 ng/L; "ineffectiveness" was > 500 ng/L. The status was defined as persistent SHPT if iPTH was > 150 ng/L after surgery. The status was considered as SHPT recurrence if iPTH was < 100 ng/L in the first week after surgery, and gradually increased and > 150 ng/L with the follow-up. RESULTS: (1) Ten patients were involved and the average dialysis time was 142 months [male/female: 4/6; age 30 - 54 (39.3 ± 10.4) years]. All patients had severe bone and joint pain, accompanied with progressive facial increases, chicken breast, kyphosis, hip bone deformities, and body height shortening. (2) Preoperative tests: the median of iPTH 2000 (1800 - 2863) ng/L; serum calcium (2.45 ± 0.21) mmol/L, phosphorus (2.19 ± 0.51) mmol/L, alkaline phosphatase (ALP) (1189.8 ± 780.0) IU/L. Two to four enlarged parathyroid glands were confirmed by ultrasound and (99)Tc(m)-MIBI parathyroid scintigraphy. (3) Surgical procedures: local or general anesthesia for PTX. Supplement with calcium and calcitriol implemented low serum calcium after PTX. (4) FOLLOW-UP: symptoms, including bone pain, muscle weakness, skin itching, and insomnia, were significantly improved after surgery. Transient hoarseness occurred in 2 cases. The iPTHs of all patients were decreased significantly after surgery. The median of iPTH was 55.5 (10 - 967) ng/L at 1 month post PTX, and was significantly less than prior to PTX (P < 0.001). Eight patients were "cure", 1 "marked effectiveness", and 1 "ineffectiveness". Two patients were persistent SHPT, and 1 died of heart failure in the 4(th) year after PTX. The development of bone deformities was stopped and malnutrition was improved in long-time follow up. The level of iPTH 135 (28 - 390) ng/L (P < 0.001), serum calcium, phosphorus, and ALP showed normal in the third year. The SHPT recurrence was appeared in the 2(nd) and 3(rd) year in 2 out of 8 patients, respectively. CONCLUSIONS: Total PTX can effectively treat SS by SHPT. It can improve prognosis for patients, such as bone pain disappearing, bone deformities stopping and malnutrition improving, etc. The level of iPTH may rise again in some patients in the future. Therefore, more attentions should be paid to monitoring.

Pharmacokinetics and pharmacodynamics of broccoli sprouts on the suppression of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: implication of induction of Nrf2, HO-1 and apoptosis and the suppression of Akt-dependent kinase pathway.

PURPOSE: In the present study, we have evaluated the pharmacokinetics and the in vivo prostate chemopreventive activity of broccoli sprouts. METHODS: The in vivo pharmacokinetic profiles of sulforaphane (SFN) and SFN- glutathione (GSH) conjugate in rats after oral administration of 200 mg and 500 mg broccoli sprouts were analyzed. Next, 8-week old TRAMP mice were fed with dietary broccoli sprouts at two dosages (60 and 240 mg/mouse/day) for 16 weeks, and the mice were sacrificed to examine the pharmacodynamic response on prostate tumor and some biomarkers. RESULTS: SFN was readily released and conjugated with GSH in the rats after oral administration of broccoli sprouts. TRAMP mice fed with 240 mg broccoli sprouts/mouse/day exhibited a significant retardation of prostate tumor growth. Western blot analysis revealed that the expression levels of Nrf2, HO-1, cleaved-Caspase-3, cleaved-PARP and Bax proteins were increased, but that of Keap1 and Bcl-XL proteins were decreased. In addition, the phosphorylation and/or the expression level of Akt and its downstream kinase and target proteins, e.g. mTOR, 4E-BP1 and cyclin D1, were reduced. CONCLUSIONS: Our findings indicate that broccoli sprouts can serve as a good dietary source of SFN in vivo and that they have significant inhibitory effects on prostate tumorigenesis.

Induction of detoxifying enzymes by garlic organosulfur compounds through transcription factor Nrf2: effect of chemical structure and stress signals.

Garlic organosulfur compounds (OSCs) are recognized as a group of potential chemopreventive compounds. It is known that garlic OSCs can modulate drug metabolism systems, especially various phase II detoxifying enzymes, though the mechanism underlying their inductive effect on these enzymes remains largely unknown. In the present study, we investigated the transcriptional levels of NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO1) genes, the reporter activity mediated by antioxidant response element (ARE), and the protein level of transcription factor nuclear factor E2-related factor 2 (Nrf2), after administration of three major garlic OSCs--diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS)--in human hepatoma HepG2 cells. Our results showed that ARE activation and Nrf2 protein accumulation were well correlated with phase II gene expression induction. The structure-activity relationship study indicated that the third sulfur in the structure of OSCs contributed substantially to their bioactivities, and that allyl-containing OSCs were more potent than propyl-containing OSCs. To better understand the signaling events involved in the upregulation of detoxifying enzymes by DATS, ARE activity and Nrf2 protein levels were examined after transient transfection of HepG2 cells with mutant Nrf2, cotreatment with antioxidants, and pretreatment with protein kinase inhibitors. DATS-induced ARE activity was inhibited by dominant-negative Nrf2 Kelch-like ECH-associating protein 1 and constructs. Cotreatment with thiol antioxidants decreased the ARE activity and Nrf2 protein level induced by DATS. Three major mitogen-activated protein kinases (MAPKs)--extracellular signal-regulated protein kinase, c-Jun N-terminal kinase, and p38--were activated by DATS treatment. However, the inhibition of these MAPKs did not affect DATS-induced ARE activity. Pretreatment with various upstream protein kinase inhibitors showed that the protein kinase C pathway was not directly involved in DATS-induced ARE activity, but instead the calcium-dependent signaling pathway appeared to play a role in the DATS-induced cytoprotective effect.