Optimized project of traditional Chinese medicine in treating chronic kidney disease stage 3: a multicenter double-blinded randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE Stage 3 is the key phase of chronic kidney disease. Traditional Chinese medicine (TCM) has been used for the treatment of chronic kidney disease. But a large sample trial is desirable. MATERIALS AND METHODS A total of 578 Chinese patients with primary glomerulonephritis in CKD stage 3 were randomly assigned to three groups: patients received TCM (TCM group), benazepril (Ben group), TCM combined with benazepril (TCM+Ben group). Patients were followed up for 24 weeks. The primary endpoint was the time to the composite of 50% increased of serum creatinine, end stage renal disease or death. RESULTS eGFR in the TCM and the TCM+Ben group were improved (week 24 vs. baseline, P<0.05) while eGFR in the Ben group was decreased (week 24 vs. baseline, P>0.05). 24h urinary protein excretion (UP) and urinary albumin/creatinine (UAlb/Cr) were decreased in the TCM+Ben (week 24 vs. baseline, P<0.05) and the Ben group (week 24 vs. baseline, P>0.05). UP and UAlb/Cr were increased in the TCM group to week 12, then were stable (week 24 vs. baseline, P<0.05). The hemoglobin in the TCM group was also improved (week 24 vs. baseline, P<0.05). The accumulative survival rate in the TCM+Ben group was higher than that in the TCM group and the Ben group (P=0.044). Side effects in the TCM group were the lowest in these groups (P<0.05). The patients with dry cough in the TCM+Ben group and the Ben group were increased as compared with the TCM group (P<0.05). Hyperkalemia happened less frequently in the TCM group as compared with the other two groups (P=0.052). CONCLUSIONS For the patients with CKD stage 3, TCM can improve eGFR and hemoglobin with lower side effects. Benazepril significantly decreased the proteinuria. Chinese medicine integrated with benazepril can ameliorate renal function and decrease proteinuria synergistically.

[1]  G. K. Chu,et al.  A Chinese herbal decoction, Danggui Buxue Tang, prepared from Radix Astragali and Radix Angelicae Sinensis stimulates the immune responses. , 2006, Planta medica.

[2]  Xiang-mei Chen,et al.  [Multicentered, randomized, controlled clinical trial on patients with IgA nephropathy of Qi-yin deficiency syndrome type]. , 2007, Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine.

[3]  G. Gallacher,et al.  Suppression of experimental autoimmune tubulointerstitial nephritis in BALB/c mice by berberine. , 2000, Immunopharmacology.

[4]  Li-sheng Liu,et al.  Association between carotid artery intima-media thickness and early-stage CKD in a Chinese population. , 2007, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[5]  T. Chan,et al.  Emodin ameliorates glucose-induced matrix synthesis in human peritoneal mesothelial cells. , 2003, Kidney international.

[6]  Sheng Wei,et al.  Triptolide inhibits extracellular matrix protein synthesis by suppressing the Smad2 but not the MAPK pathway in TGF-beta1-stimulated NRK-49F cells. , 2010, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[7]  Y. Tan,et al.  Effect of water deficits on the activity of anti-oxidative enzymes and osmoregulation among three different genotypes of Radix Astragali at seeding stage. , 2006, Colloids and surfaces. B, Biointerfaces.

[8]  Da Zhu,et al.  Astragalus mongholicus ameliorates renal fibrosis by modulating HGF and TGF-β in rats with unilateral ureteral obstruction , 2009, Journal of Zhejiang University SCIENCE B.

[9]  Di Xie,et al.  Efficacy and safety of benazepril for advanced chronic renal insufficiency. , 2006, The New England journal of medicine.

[10]  Bing Yang,et al.  Inhibition of phosphorylation of p38 MAPK involved in the protection of nephropathy by emodin in diabetic rats. , 2006, European journal of pharmacology.

[11]  Y. Iwamoto,et al.  Effects of the Renin-Angiotensin system blockade on hemoglobin levels in type 2 diabetic patients with chronic kidney disease. , 2008, American journal of hypertension.

[12]  S. K. Kim,et al.  Protective effect of Tanshinone IIA on the early stage of experimental diabetic nephropathy. , 2009, Biological & pharmaceutical bulletin.

[13]  Yan-yun Ren,et al.  [Effect of Qufengtongluo recipe on expression of nephrin mRNA in adriamycin-induced nephropathy in rats]. , 2009, Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences.

[14]  J. Lai,et al.  Immunomodulatory effects and mechanisms of plant alkaloid tetrandrine in autoimmune diseases. , 2002, Acta pharmacologica Sinica.

[15]  Ping Zhang,et al.  Assessment of the renal protection and hepatotoxicity of rhubarb extract in rats. , 2009, Journal of ethnopharmacology.

[16]  Yuzhang Wu,et al.  Triptolide inhibits B7-H1 expression on proinflammatory factor activated renal tubular epithelial cells by decreasing NF-kappaB transcription. , 2006, Molecular immunology.

[17]  Xiaoqin Wang,et al.  Salvia miltiorrhiza depresses plasminogen activator inhibitor-1 production through inhibition of angiotensin II. , 2008, The American journal of Chinese medicine.

[18]  J. Chen,et al.  [Mechanism of Chinese herbal medicine delaying progression of chronic kidney disease]. , 2009, Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica.

[19]  Liming Chen,et al.  JinQi-Jiangtang tablet, a Chinese patent medicine, for pre-diabetes: a randomized controlled trial , 2010, Trials.

[20]  Qihe Xu,et al.  In vitro anti-fibrotic activities of herbal compounds and herbs. , 2009, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[21]  C. Zeng,et al.  Triptolide protects podocytes from puromycin aminonucleoside induced injury in vivo and in vitro. , 2008, Kidney international.

[22]  L. Sy,et al.  Herbal treatment for renal diseases. , 2005, Annals of the Academy of Medicine, Singapore.

[23]  A. Levey,et al.  A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation , 1999, Annals of Internal Medicine.

[24]  Shuo Wang,et al.  Inhibitory Effect of Emodin on Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) Expression in Rat Hepatic Stellate Cells , 2006, Digestive Diseases and Sciences.

[25]  H. Oh,et al.  Lithospermic acid B isolated from Salvia miltiorrhiza ameliorates ischemia/reperfusion-induced renal injury in rats. , 2004, Life sciences.

[26]  C. Zeng,et al.  Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro. , 2010, Kidney international.

[27]  Sook-Kyoung Heo,et al.  Emodin and rhein inhibit LIGHT-induced monocytes migration by blocking of ROS production. , 2010, Vascular pharmacology.

[28]  Jiyoung Kim,et al.  Antioxidant effect of tianwang buxin pills a traditional chinese medicine formula: double-blind, randomized controlled trial. , 2009, The American Journal of Chinese Medicine.

[29]  Bianhong Zhang,et al.  Tetrandrine protects mice from concanavalin A-induced hepatitis through inhibiting NF-kappaB activation. , 2008, Immunology letters.

[30]  N. Chen,et al.  Community-based study on CKD subjects and the associated risk factors , 2009, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[31]  C. Meisinger,et al.  Effect of Chronic Kidney Disease and Comorbid Conditions on Health Care Costs: A 10-Year Observational Study in a General Population , 2009, American Journal of Nephrology.

[32]  J. Wan,et al.  The nephroprotective effects of the herbal medicine preparation, WH30+, on the chemical-induced acute and chronic renal failure in rats. , 2005, The American journal of Chinese medicine.

[33]  N. Chen,et al.  Comparison of antioxidant activities between salvianolic acid B and Ginkgo biloba extract (EGb 761) , 2006, Acta Pharmacologica Sinica.

[34]  J. Aldigier,et al.  Protection of Renal Function with ACE Inhibitors , 1998, Clinical drug investigation.

[35]  Y. Kanno,et al.  A Fiveyear Comparison of the Renal Protective Effects of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Patients with NonDiabeticNephropathy , 2006 .

[36]  Chen Wang,et al.  Effects of No.2 Renal Failure Recipe on expressions of cyclooxygenase-2 and -1 mRNAs in rats with chronic renal failure. , 2008, Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine.

[37]  N. Futrakul,et al.  A Mildly Altered Vascular Homeostasis in Early Stage of CKD , 2009, Renal failure.

[38]  Xili Wu,et al.  Clinical study of trilogy detoxicating therapy combined with routine Western medicine on patients with chronic renal failure , 2008, Chinese journal of integrative medicine.

[39]  R. Atkins,et al.  Comparison of the prevalence and mortality risk of CKD in Australia using the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study GFR estimating equations: the AusDiab (Australian Diabetes, Obesity and Lifestyle) Study. , 2010, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[40]  Ying Wang,et al.  Tetrandrine suppresses lipopolysaccharide-induced microglial activation by inhibiting NF-κB pathway , 2008, Acta Pharmacologica Sinica.

[41]  Shao-feng Yang,et al.  [Therapeutic effect of total glucosides of paeony on lupus nephritis in MRL/lpr mice]. , 2011, Nan fang yi ke da xue xue bao = Journal of Southern Medical University.

[42]  C. H. Cheng,et al.  Danshen prevents the occurrence of oxidative stress in the eye and aorta of diabetic rats without affecting the hyperglycemic state. , 2006, Journal of ethnopharmacology.

[43]  M. Yin,et al.  Nonenzymatic antioxidative and antiglycative effects of oleanolic acid and ursolic acid. , 2007, Journal of agricultural and food chemistry.

[44]  Ping-yan Chen,et al.  Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: a randomized controlled study of benazepril and losartan in chronic renal insufficiency. , 2007, Journal of the American Society of Nephrology : JASN.

[45]  Xili Wu,et al.  [Mechanism of the effect of Tongluo Recipe against glomerular sclerosis in rats]. , 2008, Nan fang yi ke da xue xue bao = Journal of Southern Medical University.

[46]  S. Donnelly,et al.  Erythropoietin deficiency in hyporeninemia. , 1999, American Journal of Kidney Diseases.

[47]  T. Yokozawa,et al.  Role of Salviae Miltiorrhizae Radix extract and its compounds in enhancing nitric oxide expression. , 2000, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[48]  Zhi-qiang Gao,et al.  Effect of emodin on pancreatic fibrosis in rats. , 2007, World journal of gastroenterology.

[49]  K. Pyun,et al.  Anti-inflammatory effects of Stephania tetrandra S. Moore on interleukin-6 production and experimental inflammatory disease models , 1996, Mediators of inflammation.

[50]  Zhigui Wu,et al.  Molecular pharmacological basis of the YiSui ShenXu Granule in beta-thalassemia therapy. , 2008, Journal of ethnopharmacology.

[51]  M. Itô,et al.  Studies on the antinephritic effect of plant components (4): Reduction of protein excretion by berberine and coptisine in rats with original-type anti-GBM nephritis. , 1992, Japanese journal of pharmacology.