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.

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.

Study of the efficacy of mizoribine in lupus nephritis in Chinese patients.

We conducted a clinical study in China on the efficacy and safety of mizoribine (MZR) in lupus nephritis. Eleven subjects with proteinuria (≥2 g/day) who had undergone renal biopsy confirming a diagnosis of lupus nephritis (class III: 1 subject; class IV: 6 subjects; class V: 4 subjects) were enrolled. Nine of the subjects were treatment- naive patients who received remission induction therapy, and the other two were switched from cyclophosphamide (CTX) or mycophenolate mofetil due to lack of efficacy. MZR 150 mg was administered once a day. After 6 months, the remission rate was 72.7% (2 subjects achieved complete remission, and 9 partial remission). After 3 and 6 months, significant reductions (p < 0.01) were obtained in 24-h proteinuria (g/day). In the subjects switched to MZR due to lack of efficacy with CTX, the dose was increased from MZR 150-200 mg due to inadequate improvement in proteinuria, and this dose escalation resulted in complete remission after 6 months. It is believed that this kind of dose escalation is one possible treatment option for lupus nephritis. In this study, no adverse events occurred in any of the subjects. We therefore concluded that this first use in China as remission induction therapy in lupus nephritis patients of MZR, which is recognized as an effective maintenance therapy in Japan, was effective. The results also suggest that MZR could be effective in patients for whom other drugs have been insufficiently effective.

[The association between vitamin D deficiency and diabetic nephropathy in type 2 diabetic patients].

OBJECTIVE: To evaluate the association between vitamin D deficiency and diabetic nephropathy in type 2 diabetic patients. METHODS: A total of 594 patients with type 2 diabetes were enrolled from the inpatients of the Nanjing Medical University Affiliated Nanjing Hospital. Fasting serum lipid profile, 25-hydroxycalciferol vitamin D and urinary albumin excretion rate were investigated. The relationship between nephropathy and vitamin D deficiency ( < 20 µg/L) or insufficiency (20-<30 µg/L) was analyzed. RESULTS: Nephropathy was found in 177 subjects (29.8%) with albuminuria in 141 and proteinuria in 36 subjects. Vitamin D deficiency was found in 180 subjects and insufficiency in 157 subjects. The proportion of vitamin D deficiency was higher in the individuals with nephropathy than those without nephropathy (36.2% vs 27.8%, P < 0.05). The urinary albumin excretion rate was significantly higher in the patients with vitamin D deficiency than those with normal vitamin D concentration [(123.0 ± 299.2) mg/24h vs (47.6 ± 97.1) mg/24h, P < 0.01]. The prevalence of nephropathy was higher in the patients with vitamin D deficiency than those with normal vitamin D concentration (35.6% vs 26.1%, P < 0.05), while the prevalence of proteinuria was higher in patients with vitamin D deficiency (12.2% vs 3.1%, P < 0.01). Logistic regression analysis demonstrated that vitamin D deficiency was associated with nephropathy (OR 1.57, 95%CI 1.04-2.37), even after the adjustment for age, gender, hypertension, dyslipidemia, smoking status, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (OR 1.78, 95%CI 1.12-2.81). The Vitamin D concentration was significantly negatively correlated with urinary albumin excretion rate (r = -1.783, P < 0.001). CONCLUSIONS: Type 2 diabetic patients have a high prevalence of vitamin D deficiency. Vitamin D deficiency is independently associated with diabetic nephropathy.

Suppression of Par-4 protects human renal proximal tubule cells from apoptosis induced by oxidative stress.

BACKGROUND: Oxidative stress is an important inducer of cell apoptosis and plays a key role in the development of renal inflammation. The prostate apoptosis response factor-4 (Par-4) gene was originally identified in prostate cells undergoing apoptosis. Subsequently, Par-4 was found to possess potent pro-apoptotic activity in various cellular systems. However, it remains unclear whether Par-4 is involved in oxidant injury of renal tubular epithelial cells. AIMS: To determine the role of Par-4 in renal proximal tubular cell apoptosis induced by oxidative stress. METHODS: Par-4 gene expression was silenced by small interfering RNA. Renal proximal tubular cells were then exposed to hydrogen peroxide and the effect of Par-4 silencing on apoptosis and expression of phosphorylated Akt and vascular endothelial growth factor was determined. RESULTS: Hydrogen peroxide induced apoptosis and increased Par-4 expression in human renal proximal tubular epithelial cells. Par-4 silencing significantly protected renal proximal tubular cells from apoptosis via activating the PI3K/Akt signaling pathway as Akt phosphorylation was enhanced. Par-4 silencing also ameliorated the downregulation of vascular endothelial growth factor expression induced by oxidative stress. CONCLUSION: Par-4 gene silencing resulted in PI3K/Akt signaling-dependent inhibition of renal proximal tubular cell apoptosis following oxidative stress.

[Liver X receptors mediate cholesterol efflux in mouse glomerular mesangial cells].

OBJECTIVE: To examine the role of liver X receptors (LXRs) in lipid metabolism in cultured mouse mesangial cells. METHODS: To determine whether LXRalpha and LXRbeta are expressed in the kidney, RT-PCR and western blot assay were utilized. Cultured mesangial cells were treated with either vehicle or LXR agonist TO901317(10 micromol/L) for 24 hours. Real-time PCR analysis was used to detect ABCA1 and ABCG1 expressions. Cells were also transfected with a human ABCA1 promoter driven luciferase reporter plasmid and then stimulated with or without TO901317 for 24 hours. In order to determine the effect of TO901317 on protein expression of ABCA1, LXRalpha adenovirus was used to overexpress LXRalpha in the cultured cells. Finally, [3H] cholesterol efflux assay was performed to evaluate the efflux of cholesterol upon TO901317 stimulation. RESULTS: Both LXRalpha and LXRbeta were expressed in the kidney, freshly isolated glomeruli and mesangial cells. After treatment with TO901317, both ABCA1 and ABCG1 expressions were induced. Moreover, ABCA1 protein level was increased after the cells were simultaneously treated with LXRalpha-adenovirus and TO901317. The cholesterol efflux was also significantly enhanced after TO901317 treatment. CONCLUSION: LXRalpha and LXRbeta were functionally expressed in mouse mesangial cells. Activation of LXRs enhanced cholesterol efflux possibly through upregulating ABCA1 and ABCG1 expressions in mesangial cells. Therefore, LXR agonist might ameliorate lipid accumulation and reduce related cell injury in mesangial cells.