Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg. MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER: NCT02063100 on ClinicalTrials.gov.

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).

[Two new polypeptides from extract of deer bone extract].

Two new polypeptides were isolated and purified from the extract of deer bone (constitutive part of Cucumis and Cervus polypeptide injection) by various column chromatography including C4 300Å and Sephadex G-50, as well as semipreparative HPLC. Their N-terminal amino acid sequences were identified by De Novo sequencing on the basis of MALDI-TOF-MS data and Explorer™ software. The N-terminal amino acid sequences of polypeptides were identified as NH2-Gly-Pro-Val-Gly-Pro-Thr-Gly-Pro-Val-Gly-Ala-Ala-Gly-Pro-Ser-Gly-Pro-Asp (Mei18 peptide, 1) and NH2-Ala-Gly-Pro-Ala-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Pro-Asp-Ser-Try-Asp (Mei23 peptide, 2), respectively. Mei18 and Mei 23 peptides are new polypeptides.

Clinical study on Yishen Qufeng Shengshi Recipe () for glomerular proteinuria patients: A randomized controlled trial.

OBJECTIVE: To explore the therapeutic effect of Yishen Qufeng Shengshi Recipe (, YQSR) in patients with glomerular proteinuria METHODS: A total of 145 patients with glomerular proteinuria were selected and randomly assigned to the treatment group (108 cases) and the control group (37 cases) according to a random number table in a ratio of 3:1. All patients received conventional and symptomatic treatment. In addition, patients in the treatment and control groups were given YQSR (200 mL, twice per day, orally) and losartan (50 mg/d orally), respectively for 6 months. The 24-h urine protein quantity, blood urea nitrogen, and serum creatinine in the two groups were measured at multiple time points before and after treatment. RESULTS: At the end of the study, 5 cases were lost to follow-up in the treatment group and 1 in the control group. Finally, the statistical data included 103 cases in the treatment group and 36 cases in the control group. The total effectiveness after 2, 4, and 6 months was 81.6% (84/103), 87.4% (90/103), and 92.2% (95/103), respectively, in the treatment group and 47.2% (17/36), 55.6% (20/36), and 61.1% (22/36), respectively, in the control group, with significant difference between the two groups (P<0.01 at all observation points). In the treatment group, the curative effect after 6 months was better than that after 2 months (P<0.05). The 24-h urine protein quantity was significantly lower in the treatment group at 3, 4, 5, and 6 months than that in the control group (P<0.05 or P<0.01, respectively) CONCLUSION: YQSR could significantly reduce the amount of glomerular proteinuria in the early stage.

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.

[Effects of Gubentongluo Formula on Oxidative Stress Reflected by Expressions of PPARα and L-FABP in Mice with IgA Nephropathy].

OBJECTIVES: To determine the underlying mechanism of Gubentongluo Formula in the treatment of IgA nephropathy (IgAN). METHODS: C57BL/6 mice were randomly divided into four groups: normal group (n =10), IgAN group (n =10), control group (n =10) and treatment group (n =10). Mice in the normal and IgAN groups were intragastricly administered with normal saline for 12 weeks; while those in the control and treatment groups were given fenofibrate [30 mg/(kg!$d) and Gubentongluo Formula [1.67 mL/(g!$d)], respectively. Urinary albumin was detected at week 0 and 12. At week 12, protein expressions of peroxisome proliferstor activated receptor α (PPARα), liver fatty acid-binding proteins (L-FABP), 4-hydroxy-2-nonenal (4-HNE), and hemeoxygenase-1(HO-1) in renal tissues were determined by Western blot; mRNA expressions of PPARα and L-FABP in renal tissues were determined by florescent quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: At week 12, higher levels of urinary albumin, pathological injuries in glomerular mesangial area, and lower expressions of protein and mRNA of PPARα and L-FABP were found in mice in the IgAN group compared with those in the normal group (P <0.01). The levels of those indicators decreased in those treated with fenofibrate and Gubentongluo Formule, but still higher than the normal controls (P <0.01). The mice treated with Gubentongluo Formula had more significant improvement than those treated with fenofibrate (P <0.05). CONCLUSION: [CM(155.3mm]Gubentongluo formula can improve proteinuria and pathological injuries in glomerular mesangial area of IgAN mice, due to reduction of oxidative stress in renal tissues through regulating the expressions of PPARα and L-FABP.

[Effect of Kangxianling Recipe on p38MAPK/NF-KBp65 Mediated Inflammatory Factors in 5/6 Nephrectomized Mice].

Objective To observe effects of Kangxianling Recipe ( KXLR) on p38MAPK/NF- κBp65 mediated inflammatory factors in chronic renal failure ( CRF) model mice. Methods Totally 56 C57BL/6J male mice (18 -22 g) were recruited in this experiment. Ten were randomly selected as a sham-operation group. The rest 46 mice were used for preparing CRF model by 5/6 nephrectomization. To- tally 33 successfully modeled mice were divided into the model group, the rapamycin (RAP) group, and the KXLR group according to serum creatinine (SCr) level, 11 in each group. Mice in the RAP group were administered with rapamycin (0.13 mg/100 g per day, 0. 5 mL each time) by gastrogavage. Mice in the KXLR group were administered with KXLR (2 g/100 g per day, 0. 5 mL each time) by gastrogavage. Equal volume of distilled water was administered to mice in the model group and the sham-operation group. Mice were sacrificed after 8 weeks of consecutive medication. The expression of neutrophils was ob- served using immunohistochemical assay. Expression levels of p38MAPK/NF-κB p65 protein and TNF-α/ IL-6 mRNA were detected by Western blot and Real-time PCR. Results Compared with the sham-opera- tion group, the number of positive neutrophils increased, expression levels of p38MAPK/NF-κB p65 protein and TNF-α/IL-6 mRNA were enhanced significantly in the model group (P <0. 05, P <0. 01). Com- pared with the model group, the number of neutrophils was reduced, expression levels of p38MAPK/NF- κB p65 protein and TNF-α/IL-6 mRNA were decreased significantly in the KXLR group and the RAP group (P <0. 05, P <0. 01). RAP showed better effect in decreasing p38MAPK protein expression than KXLR (P <0. 05). There was no statistical difference in the rest indices between the KXLR group and the RAP group (P >0. 05). Conclusions KXLR participated the regulation of p38MAPK/NF-κB p65 mediated in- flammation factors. It had certain improvement in renal fibrosis induced renal failure.

[Effect of "Gubentongluo Formula" on the IgA Class Switch Recombination of B Lymohocytes in Peyer's Patches in Mice with IgA Nephropathy].

OBJECTIVE: To explore the underlying mechanism of "Gubentongluo Formula" in treatment of IgA nephropathy (IgAN). METHODS: After the IgAN model was successfully induced at week 12, the Kunming mice were randomly divided into three groups: normal control group (n = 15), IgAN group (n = 15) and Traditional Chinese Medicine (TCM) group. The mice in normal control and IgAN group were intragastriclly administrated with normal saline for 8 weeks; meanwhile, the mice in TCM group were intragastriclly administrated with "Gubentongluo Formula" 1.35 mL/ (g · d). The levels of 24 h urine protein were determined at Week 0, 12 and 20. At week 20, the changes of renal pathology were detected; the mRNA expressions of transforming growth factor-ß (TGF-ß) and small mothers against decapentaplegic (Smad) 3 in Peyer's patches (PPs) were detected by fuorescent quantitative reverse transcription-polymerase chain reaction; the protein expressions of TGF-ß and Smad 3 in PPs were detected by immunohistochemistry technique; the levels of (IgA + B)/B lymphocytes in PPs were determined by flow cytometry. RESULTS: Compared with those results of normal control group, the levels of 24 h urine protein, IgA deposition in glomerular mesangial area, and expressions of protein and mRNA of TGF-ß and Smad3 in IgAN group were significantly increased (P < 0.01). Besides, the levels of (IgA+B)/B lymphocytes were significantly elevated in IgAN group (P < 0.01). All these indicators were improved in TCM group. Compared with IgAN group, the differences were statistically significant (P < 0.01). Compared with those results of control group, the levels of (IgA + B)/B lymphocytes showed no significant difference in TCM group (P > 0.05), but other indicators showed significant differences (P < 0.01). CONCLUSION: "Gubentongluo Formula" could effectively improve proteinuria and suppress IgA deposition in glomerular mesangial area in IgAN mice, due to affect IgA class switch recombination of B lymphocytes in PPs through regulating TGF-ß/Smad3 pathway.

Prevalence, awareness, and treatment of anemia in Chinese patients with nondialysis chronic kidney disease: First multicenter, cross-sectional study.

This was the first multicenter, cross-sectional survey to assess the prevalence of anemia, patient awareness, and treatment status in China. Data of patients with chronic kidney disease (CKD; age, 18-75 years; both out- and inpatients) from 25 hospitals in Shanghai, seeking medical treatment at the nephrology department, were collected between July 1, 2012 and August 31, 2012. The prevalence, awareness, and treatment of anemia in patients with nondialysis CKD (ND-CKD) were assessed. Anemia was defined as serum hemoglobin (Hb) levels ≤12 g/dL in women and ≤13 g/dL in men. A total of 2420 patients with ND-CKD were included. Anemia was established in 1246 (51.5%) patients: 639 (51.3%) men and 607 (48.7%) women. The prevalence of anemia increased with advancing CKD stage (χtrend = 675.14, P < 0.001). Anemia was more prevalent in patients with diabetic nephropathy (68.0%) than in patients with hypertensive renal damage (56.6%) or chronic glomerulonephritis (46.1%, both P < 0.001). Only 39.8% of the anemic patients received treatment with erythropoietin and 27.1% patients received iron products; furthermore, 22.7% of the patients started receiving treatment when their Hb level reached 7 g/dL. The target-achieving rate (Hb at 11-12 g/dL) was only 8.2%. Of the 1246 anemia patients, only 7.5% received more effective and recommended intravenous supplementation. Anemia is highly prevalent in patients with ND-CKD in China, with a low target-achieving rate and poor treatment patterns. The study highlights the need to improve multiple aspects of CKD management to delay the progression of renal failure.

A Meta-Analysis of Randomized Controlled Trials of Yiqi Yangyin Huoxue Method in Treating Diabetic Nephropathy.

Objective. The purpose of this systematic review is to evaluate the evidence of Yiqi Yangyin Huoxue Method for diabetic nephropathy. Methods. 11 electronic databases, through September 2015, were searched to identify randomized controlled trials of Yiqi Yangyin Huoxue Method for diabetic nephropathy. The quality of the included trials was assessed using the Jadad scale. Results. 26 randomized controlled trials were included in our review. Of all the included trials, most of them were considered as high quality. The aggregated results suggested that Yiqi Yangyin Huoxue Method is beneficial to diabetic nephropathy in bringing down the microalbuminuria (SMD = -0.98, 95% CI -1.22 to -0.74), serum creatinine (SMD = -0.56, 95% CI -0.93 to -0.20), beta-2 microglobulin (MD = 0.06, 95% CI 0.01 to 0.12), fasting plasma glucose (MD = -0.35, 95% CI -0.62 to -0.08), and 2-hour postprandial blood glucose (MD = 1.13, 95% CI 0.07 to 2.20), but not in decreasing blood urea nitrogen (SMD = -0.72, 95% CI -1.47 to 0.02) or 2-hour postprandial blood glucose (SMD = -0.48, 95% CI -1.01 to 0.04). Conclusions. Yiqi Yangyin Huoxue Method should be a valid complementary and alternative therapy in the management of diabetic nephropathy, especially in improving UAER, serum creatinine, fasting blood glucose, and beta-2 microglobulin. However, more studies with long follow-up are warrant to confirm the current findings.

Interventional mechanisms of herbs or herbal extracts on renal interstitial fibrosis.

Renal interstitial fibrosis (RIF) is a common development in chronic renal diseases that can lead to uremia and be life-threatening. The RIF pathology has complicated extracellular and intercellular mechanisms, involving many cells and cytokines, resulting in an incomplete mechanistic understanding of the disease. Finding effective herbs or herbal extracts for prevention and treatment of RIF is crucial because current medical approaches do not reliably slow or reverse RIF. In recent years, many experts have worked to identify herbs or herbal extracts to combat RIF both in vivo and in vitro, with some success. This review attempts to summarize the possible interventional mechanisms of herbs or herbal extracts involved in protecting and reversing RIF. The authors found some herbs and their extracts that may ameliorate renal impairments through anti-inflammation, anti-fibrogenesis and stabilization of extra cellular matrix. Among them, tetramethylpyrazine/ligustrazine, curcumin and polyglucoside of Tripterygium have experimentally shown good potential for improving RIF. However, conclusive evidence is still needed, especially in randomized controlled clinical trials. We expect that herbs or herbal extracts will play an important role in RIF treatment and reversal in the future.

A Clinical Multicenter Randomized Controlled Study on JianpiQinghua Decoction in Treating Stage 3 Chronic Kidney Disease with A Syndrome Type of Dampness-heat due to Spleen Deficiency.

Objective To evaluate the clinical effectiveness of JianpiQinghua decoction in treating stage 3 chronic kidney disease (CKD3) with syndrome type of dampness-heat due to spleen deficiency. Methods A multicenter, randomized, controlled, prospective, double-blind, and double-simulation study was undertaken. A total of 270 CKD3 patients with syndrome type of dampness-heat due to spleen deficiency from the outpatient departments of six general hospitals were randomly divided into telmisartan+analog traditional Chinese medicine (TA) group, traditional Chinese medicine+analog telmisartan (TCMA) group, and telmisartan+traditional Chinese medicine (TTCM) group, in which the corresponding treatment was applied in addition to basic treatment. Six months later, changes in the traditional Chinese medicine (TCM) clinical symptom scores and renal functions before and after treatment were compared among these three groups. Results Of these 270 CKD3 patients who had been enrolled in this study, 30 cases lost to follow-up. The baseline data were comparable among these three groups. After treatment, the TCM clinical symptom scores of both syndrome of spleen-qi deficiency and dampness-heat in TA group were significantly higher than those in TCMA group and TTCM group (P<0.001). With the treatment time prolonged, the TCM clinical symptom scores showed similar descending trends in TCMA group and TTCM group but were different from that in TA group. After treatment, abnormal creatinine rate decreased (P=0.003), and these three treatments and their interactions with each visit had no effect on serum urea nitrogen value (P=0.270, P=0.520); with prolonged treatment, the estimated glomerular filtration rates in three groups tended to be relatively stable after the first rise. The liver function and abnormal serum potassium rate were not statistically significant before and after treatment (P>0.05). Conclusions JianpiQinghua decoction can improve clinical symptoms of TCM in CKD3 patients with syndrome type of dampness-heat due to spleen deficiency and thus improve the quality of life and prognosis. The clinical efficacy of JianpiQinghua decoction alone or combined with telmisartan is superior to telmisartan monotherapy.

[Treatment of Proteinuria in Chronic Glomerular Disease Patients with Pi-Shen Deficiency Complicated Damp-Heat Syndrome by Yishen Qingre Huashi Recipe: a Clinical Study].

OBJECTIVE: To observe the therapeutic effect of Yishen Qingre Huashi Recipe (YQHR) in treating proteinuria of chronic glomerular disease patients with Pi-Shen deficiency complicated damp-heat syndrome (PSDCDHS). METHODS: Totally 121 stage 1 -2 primary chronic glomerular disease patients with PSDCDHS were randomly assigned to the treated group (85 cases) and the control group (36 cases) according to 2:1. All patients received conventional and symptomatic treatment. Patients in the treated group took YQHR additionally, while those in the control group took Losartan Potassium Tablet (50 mg each time, once per day) additionally. The therapeutic course for all was 6 months. Changes of 24 h urine protein, blood urea nitrogen (BUN), serum creatinine(SCr), and estimated glomerular filtration rate (eGFR) were observed at different time points. And the difference in therapeutic effects were compared between the two groups. RESULTS: Compared with the control group after 6 months of treatment, 24 h urine protein obviously decreased in the treated group (P <0. 05). There was no statistical difference in SCr, BUN, or eGFR between the two groups after 6 months of treatment (P >0. 05). The total effective rate after 2, 4, and 6 months of treatment in the treated group was 77. 6% (66/85 cases), 82. 4% (70/85 cases), and 89. 4% (76/85 cases), respectively. They were 47. 2% (17/36 cases), 55. 6% (20/36 cases), and 61. 1% (22/36 cases) in the control group, respectively. Compared with before treatment in the treated group, the total effective effect after 6 months of treatment was higher than that after 2 months of treatment (χ2=4. 28, P <0. 01). Compared with the control group at the same time points, the total effective rate in the treated group after 2, 4, and 6 months of treatment was higher (χ2=10. 87, 9. 53, 13.16, P <0. 01). CONCLUSION: YQHR could significantly lower proteinuria in chronic glomerular disease patients with PSDCDHS, improve the clinical effect, thereby providing clinical evidence for treating chronic glomerular disease proteinuria from resolving dampness and clearing heat.

[Multi-center randomized control study on the effects of syndrome differentiated traditional Chinese medicine therapy on CKD 1-2 with chronic nephritis proteinuria].

OBJECTIVE: To determine the effects of Syndrome Differentiated Chinese Medicine (TCM) Therapy on (CKD) 1-2 stage chronic kidney disease with proteinuria. METHODS: A prospective randomized control study was undertaken in 11 centers. A total of 396 chronic nephritis patients were divided into a treatment group (n=297) and a control group (n=99). Their TCM syndrome was classified as "Qi and Yin Deficiency of spleen and kidney" or "Qi and Yang Deficiency of spleen and kidney", with accompanying syndromes showing as "water and dampness", "damp-heat", and "blood stasis". Patients in the treatment group took a dose of Chinese medicine daily in response to their syndromes, while the controls took 50 mg/d losartan. The course of treatment was 24 weeks. Changes of 24-hour urinary protein excretion and glomerular filtration rate (eGFR) before and after treatments (4, 8, 12, 16, 20, 24 weeks), as well as clinical efficacy (after 4, 16, 24 weeks treatments) were measured. RESULTS: 361 patients were included in the final program participants comply analysis (PPS). Patients in the treatment group showed gradual decreased 24-hour urinary protein excretion, whereas the controls remained unchanged. Significant differences in 24-hour urinary protein excretion appeared between the experimental and control group at week 20 and 24 (P<0.05). eGFR decreased in all of the patients after treatments (P=0.0014). At three follow-up points, patients in the treatment group had higher eGFR than the controls, but without statistical significance (P>0.05). Significant differences in clinical remission rate, marked effect rate and total effective rate were observed between the treatment and control groups at week 24 (P<0.001). CONCLUSION: Syndrome differentiated TCM therapy can reduce the level of proteinuria in CKD 1-2 nephritis patients, promoting clinical effectiveness and protecting renal functions.

[Effects and mechanism of "Jianpi Qinghua Decoction" on renal fibrosis in rats with glomerulosclerosis].

OBJECTIVE: To investigate the mechanism of "Jianpi Qinghua Decoction" (JQD) on renal fibrosis by observing the impact of JQD on serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and kidney tumor necrosis factor-Α (TNF-Α) expressions in focal segmental glomerulosclerosis rats induced by nephrectomy combined with adriamycin. METHODS: Totally 56 male SD rats were divided into normal group, sham operation group, model group, JQD group, Yiqi Jianpi group, Qingre Huashi group, and Niaoduqing group (all n=8). The model of focal segmental glomerulosclerosis was established by the unilateral nephrectomy and the injection of adriamycin in caudal vein of rat at a dose of 3 mg/kg in the latter 5 groups. JQD, the disassembled prescription of Jianpi Qinghua Decoction (Yiqi Jianpi Decoction and Qingre Huashi Decoction), and Niaoduqing Capsule were administered separately for 8 weeks. The serum TC, TG, LDL, and VLDL levels and the expression of Kidney TNF-Α were determined. RESULTS: Compared with normal group and sham operation group, the serum TC, TG, LDL, and VLDL levels and the kidney TNF-Α expression in the model group were significantly higher (all P<0.01). Compared with the model group, the JQD group, Qingre Huashi group, and Niaoduqing group had significantly lower serum TC, TG, LDL, and VLDL levels and kidney TNF-Α expression (all P<0.01). Compared with the model group, the Yiqi Jianpi group had significantly lower serum TC ,TG, and VLDL levels (all P<0.01), while the serum LDL level and kidney TNF-Α expression remained unchanged (all P>0.05). CONCLUSIONS: JQD can regulate serum lipids and lower the TNF-Α expression in kidney tissue and thus improve the renal inflammation and relieve renal fibrosis. The heat-clearing and dampness-removing herbs in the prescription play a central role in fighting against renal fibrosis.

[Effect and mechanism of jianpi qinghua recipe on renal functions of adriamycin-induced nephropathic rats from the angle of inhibiting renal fibrosis].

OBJECTIVE: To explore the effect of Jianpi Qinghua Recipe (JQR) on renal functions of adriamycin-induced focal segmental glomerular sclerosis (FSGS) rats from the angle of activating fibroblasts to myofibroblast (MyoF). METHODS: Totally 56 rats were randomly divided into the normal control group (n=8), the sham-operation group (n =8), and the model group (n=40). The FSGS rat model was induced by nephrectomy of left kidney plus intravenous injection of adriamycin. Successfully modeled rats were further divided into 5 groups, i.e., the model group, the JQR group, the JPR (Jianpi Recipe) group, the QHR (Qinghua Recipe) group, and the NDQ (Niaoduqing) group, 8 in each group. Corresponding drugs were administered to rats in all groups, 2 mL each time, for 56 days. The effect of JQR on serum creatinine (SCr), urea nitrogen, 24-h urinary protein excretion, a-smooth muscle actin (alpha-SMA) mRNA, collagen type III (Col III) mRNA, fibronectin (FN) mRNA, and collagen type IV (Col IV) mRNA were observed. RESULTS: JQR could significantly lower SCr, urea nitrogen, and 24-h urinary protein excretion levels (P < 0.01), and significantly decrease mRNA levels of alpha-SMA, Col III, FN, and Col IV (P < 0.01). It was advantageous over the NDQ group. Compared with JPR, the relative expression levels of Col III mRNA and FN mRNA of JQR and QHR were significantly lower (P < 0.01). CONCLUSIONS: JQR could improve the renal function and renal fibrosis in the adriamycin-induced nephropathic model rats. Its efficacy was superior to that of NDQ. Its mechanisms might be linked with inhibiting activation of fibroblasts.

Efficacy and safety of Abelmoschus manihot for primary glomerular disease: a prospective, multicenter randomized controlled clinical trial.

BACKGROUND: Abelmoschus manihot, a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess its efficacy and safety in patients with primary glomerular disease. STUDY DESIGN: Prospective, open-label, multicenter, randomized, controlled, clinical trial. SETTING & PARTICIPANTS: From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. INTERVENTIONS: A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50mg/d. The duration of intervention was 24 weeks. OUTCOMES & MEASUREMENTS: The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. RESULTS: Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot, losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2, respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of -508, -376, and -545 mg/d, respectively (P=0.003 for A manihot vs losartan and P<0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups (P>0.05), and there were no severe adverse events in any group. LIMITATIONS: Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. CONCLUSIONS: A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.

[Effects of Jianpi Qinghua Decoctions on immune inflammatory injury in adriamycin-induced nephropathic rats MA].

OBJECTIVE: To investigate the effects of Jianpi Qinghua Decoctions on the inflammation injury mediated by the cellular immunity in the focal segmental glomurular Sclerosis (FSGS) nephropathy rats. METHODS: The FSGS nephropathy rat model was established by the method of intravenous injection of Adriamycin after the removal of one kidney. After the treatment of Jianpi Qinghua Decoctions, the blood, spleen and kidney samples of each rat were collected for the detection of splenocytes CD4+/CD8+ ratio, renal tubulointerstitial fibronectin (FN) mRNA, Col III mRNA, and the expression levels of TNF-alpha and IL6. RESULTS: The treatment of Jianpi Qinghua Decoctions decreased the levels of CD4+/CD8+, tubulointerstitial FN mRNA, Col III mRNA, TNF-alpha and IL6 significantly in FSGS nephropathy rats. CONCLUSION: Jianpi Qinghua Decoctions could improve renal FSGS damage in adriamycin-induced nephropathy rats.

[MAPK p38 pathway may be involved in renal function improvement in chronic renal failure rats treated with Jianpi Qinghua decoction].

OBJECTIVE: To investigate the involvement of MAPK p38 pathway in treatment of chronic renal failure with Jianpi Qinghua Decoction in rats. METHODS: Forty SPF SD rats were divided into sham group (n=10),model group (n=10), Jianpi Qinghua group (n=10) and losartan group (n=10). Rat chronic renal failure was induced by 5/6 nephrectomy (Platt method) in model, Jianpi Qinghua and losartan groups, and rats in sham group received sham operation. Jianpi Qinghua decoction (3.9 g 200 g(-1)) or losartan (3.3 g 200 g(-1)) daily were administrated by gavage in Jianpi Qinghua and losartan groups for 60 days, respectively, Rats in sham and model groups were orally administered with saline of the same volume. The serum levels of creatinine and urea nitrogen were measured by biochemical method, the expression of MAPK p38 was detected by Western Blot,and renal pathological changes were observed with hematoxylin-eosin staining. RESULTS: Compared to model group,serum creatinine levels after 60d in Jianpi Qinghua and losartan groups were decreased significantly (42.67 ± 5.98 or 40.90 ± 5.07 compared with 60.90 ± 9.54, both P<0.01), the expression of MAPK p38 was significantly down-regulated (0.555 ± 0.004 or 0.587 ± 0.045 compared with 0.930 ± 0.265,both P<0.01) and serum urea nitrogen was also decreased (8.56 ± 0.75 or 7.97 ± 0.86 compared with 8.62 ± 0.62,both P<0.05). The renal pathology in the model group presented glomerular mesangial proliferation,hyperplasia of glomenrulus mesangial cells and interstitial inflammation. Those pathological changes were attenuated significantly in Jianpi Qinghua and losartan groups. CONCLUSION: Jianpi Qinghua Decoctions can improve the renal function and renal pathological changes in a rat with chronic renal failure, which may be associated with down-regulation of MAPK p38 immune inflammatory pathways.

[The research on xiaochalhu decoction improving the inflammation of chronic glomerulonephritis patients and relieving the proteinuria].

OBJECTIVE: To observe the balance of T help cell1/2 (Th1/Th2), the changes of correlated proinflammatory cytokines (IFN-gamma and IL-4), and regulated on activation normal T cell expressed and secreted (RANTES), and the abnormal expression of IL-17, the effector of T help cell17 (Th17) in chronic glomerulonephritis (CGN)patients with Shaoyang disease, thus revealing the mechanisms of Xiaochaihu Decoction (XD) for treating proteinuria of CGN patients according to the theory of mediating Shaoyang meridian. METHODS: Totally 70 CGN patients with Shaoyang disease were randomly assigned to two groups, the treatment group (treated by XD) and the control group [treated by Shenyan Kangfu Tablet (SKT)], 35 in each group. Besides, 20 healthy volunteers were recruited as the healthy control group. Besides, routine therapy of chronic kidney disease (CKD), patients in the treatment group and the control group were treated with XD and SKT respectively for 4 weeks. The changes of Chinese medical syndrome, the effectiveness, 24-h urinary protein, renal functions, the peripheral blood IFN-gamma, IL-4, Th1/Th2, IL-17, and RANTES were compared. RESULTS: Before treatment the Th1/Th2, IL-17, and RANTES of the two treated groups were higher, and the IL-4 level was lower than those of the healthy control group (P < 0.05). After treatment the improvement of Chinese medical syndrome, main symptoms, the effectiveness was better in the XD group than in the SKT group (P < 0.05, P < 0.01). The proteinuria obviously decreased in the treatment group, with the efficacy superior to the SKT group (P < 0.05). The Th1/Th2, IL-17, and RANTES decreased to various degrees when compared with the SKT group (P < 0.05, P < 0.01). The IL-4 level increased more obviously in the treatment group than in the control group (P < 0.05). There was no statistical difference in the improvement of the renal function (P > 0.05). CONCLUSIONS: The immune disorder of the CGN patients with Shaoyang disease was correlated with Th1/Th2 imbalance, and abnormal changes of Th17 cell functions and RANTES. XD could improve the inflammation by regulating the immune disorder of CGN patients with Shaoyang disease, which proved that the theory of mediating Shaoyang meridian could be used to improve the inflammation of CGN patients, thus relieving the proteinuria.