Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine：Membranous Nephropathy / 中国实验方剂学杂志

Traditional Chinese medicine （TCM） is a great treasure house， exhibiting unique advantages in the treatment of some difficult and critical diseases. The incidence rate of membranous nephropathy has increased year by year in recent years， and has become the first cause of primary glomerular diseases. However， its pathogenesis is not clear. Modern medicine often uses immunosuppressive therapy， but it often faces the problems of high side effects and high recurrence rate. The China Association of Chinese Medicine （CACM） invited clinical experts of TCM and western medicine to fully discuss membranous nephropathy， which was later confirmed to be one of the clinical diseases responding specifically to TCM. Apart from summarizing the pathogenesis and clinical diagnosis and treatment of membranous nephropathy in both TCM and western medicine， this paper also detailed TCM cognition， syndrome differentiation， and therapeutic schemes of membranous nephropathy， aiming to improve the clinical remission rate of membranous nephropathy and provide reference for its clinical treatment.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial / 中西医结合学报

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 m@*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 / 中国结合医学杂志

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•1.73 m, 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•1.73 m, 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•1.73 m 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).

Type I and Ⅱ Cardiorenal Syndrome-related Biomarkers / 中国实验方剂学杂志

The physiology and pathology of the heart and kidney are interdependent and interact with each other, and dysfunction of any one of them causes dysfunction of the other, namely cardiorenal syndrome, in which type I and type Ⅱ have the highest incidence rate and are the commonest in clinic. Traditional Chinese medicine has a long history of treating the cardiorenal syndrome. It believes that the disease is located in the heart and kidney, and Wenyang Yiqi, Huoxue Lishui and other methods shall be adopted to effectively improve the heart and kidney function of patients. However,the pathogenesis of cardiorenal syndrome is complicated, and the clinical manifestations are diverse, which makes it difficult to diagnose and treat in the early stage, and causes missing of the best intervention timing and a poor prognosis. Biomarkers play a vital role in predicting the occurrence and development of cardiorenal syndrome. Therefore, efforts shall be made to look for biomarkers with better specificity and sensitivity, accurately evaluate physiological and pathological changes in heart and kidney, so as to achieve early diagnosis and early intervention of cardiorenal syndrome, and improve the effect of disease diagnosis and treatment. At present, domestic and foreign scholars have studied and applied more markers mainly in renal tubular injury, including neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and urinary interleukin-18. In addition, other studies have found cell cycle arrest inducing factors, such as insulin-like growth factor binding protein 7, tissue inhibitor metallo proteinase-2, and fibroblast growth factor 23 associated with mineral metabolism. The increase of the content of these biomarkers in the body is earlier than the rise of serum creatinine, which can better predict the occurrence of early cardiorenal syndrome, and has a high application value and research value. After summarization of the biomarkers relating to type I and Ⅱ cardiorenal syndrome in domestic and foreign literatures, the research progress of several representative markers were reviewed to provide reference for related research.

Effect of shenshuning recipe on the extracellular matrix accumulation of the peritoneal fibrosis rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Shenshuning Recipe (SR) on the peritoneal function, accumulation of extracellular matrix (ECM), and the expression of transforming growth factor-beta1 (TGF-beta1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the peritoneal fibrosis rats.</p><p><b>METHODS</b>The peritoneal fibrosis correlating peritoneal dialysis SD rat model was induced by injecting erythromycin and peritoneal dialysate. They were randomly divided into 4 groups according to body weight, i.e., the 1.50% peritoneal dialysate group (Group B), the 1.50% peritoneal dialysate + SR group (Group C), the 4.25% peritoneal dialysate group (Group D), and the 4.25% peritoneal dialysate +SR group (Group E), 15 in each group. Besides, another 15 rats was taken as the blank control group (n = 15, Group A). SR at the daily dose of 43.93 g/kg was given to rats in Group C and E by gastrogavage, while equal volume of normal saline was given to rats in other groups by gastrogavage. The changes of glucose in the peritoneal fluid were detected. The ultra filtration volume (UF)and mass transfer of glucose (MTG) were calculated. The pathomorphological changes of the peritoneum were observed. The distribution of collagen fiber, fibroblast count, collagen I (Col I), expressions of TIMP-1 and TGF-beta1 were determined.</p><p><b>RESULTS</b>At the end of the 6th week, statistical difference was shown in UF [(-3.3 +/- 14.2) mL] and [(-2.0 +/- 10.7) mL], MTG [(18.1 +/- 0.8) mmol/kg] and [(16.1 +/- 1.2) mmol/kg], collagen fiber [(4 721.3 +/- 541.0)%] and [(6502.7 +/- 877.4)%], fibroblast [(0.087 +/- 0.010)/mm2] and [(0.131 +/- 0.042)/mm2], Col I [(187.5 +/- 36.9)%] and [(289.7 +/- 95.6)%], TIMP-1 [(2.57 +/- 0.94)%] and [(3.63 +/- 0.29)%], and TGF-beta1 [(104.0 +/- 20.7) ng/L] and [(108.2 +/- 17.5) ng/L] between Group C and Group E, when compared with the peritoneal dialysate group at the same concentration (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>SR could postpone the development of peritoneal fibrosis in peritoneal dialysis SD rats possibly through inhibiting expressions of TGF-beta1 and TIMP-1, and hindering the over-accumulation of ECM.</p>

Effects of Shensu II Recipe on the expressions of transforming growth factor-beta1, and plasminogen activator inhibitor-1 in the focal segmental glomerulosclerosis rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effects of Shensu II Recipe on the renal function, mesangial extracellular matrix (ECM) accumulation, the expressions of transforming growth factor-beta1, (TGF-beta1), and plasminogen activator inhibitor-1 (PAI-1) in the focal segmental glomerulosclerosis (FSGS) rats.</p><p><b>METHODS</b>FSGS SD rat model was induced by injecting adriamycin. They were randomly divided into the model group, the Western medicine group, and the Chinese medicine group according to body weight. Besides, another 12 rats was taken as the blank control group. Of them, benazepril (0.33 mg/100 g) was given to rats in the Western medicine group by gastrogavage, while Shensu II Recipe (3.5 g/100 g) was given to rats in the Chinese medicine group by gastrogavage. Normal saline was given to rats in the control group and the model group by gastrogavage. Six rats died during the experiment process, among which, one in the control group, two in the model group, one in the Western medicine group, and two in the Chinese medicine group. The changes of 24 h urinary protein (24 hU, pyrogallol red method), blood urea nitrogen (BUN, urease method), serum creatinine (SCr, enzymatic assay of creatinine), serum total protein (TP, biuret colorimetry), serum albumin (ALB, bromocresol green colormetry) were detected. The pathomorphological changes of the glomerulus were observed. Fibronection (FN), collagen IV (Col IV), glomerulus sclerosis index (GSI), ECM/glomerulus area (GA), expressions of TGF-beta1, and PAI-1 were determined by semi-quantitative analysis.</p><p><b>RESULTS</b>At the end of the 12th week, improvement was shown in the Chinese medicine group (24 hU: 38.55 +/- 2.49 mg; BUN:10.87 +/- 1.78 mmol/L; SCr: 51.70 +/- 1.50 micromol/L; TP: 68.28 +/- 2.31 g/L; and ALB: 42.43 +/- 1.95 g/L). The pathomorphological observation showed that the development of glomerulosclerosis (GS) was significantly slowed down. Semi-quantitative analysis showed significant difference when compared with the model group (GSI: 1.68 +/- 0.33 grade; ECM/GA: 7.11% +/- 2.46%; FN: 4.15% +/- 1.55%; Col IV:1.47% +/- 0.48%; TGF-beta1:19.70% +/- 5.05%; PAI-1: 22.57% +/- 10.65%) ( P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>Shensu II Recipe could postpone the development of GS in FSGS rats possibly through inhibiting the expressions of TGF-beta1 and PAI-1, hindering the over-accumulation of mesangial matrix.</p>