激素联合来氟米特或环磷酰胺治疗慢性进展性IgA肾病的比较

目的：比较激素联合环磷酰胺（CTX）或来氟米特 （LEF）治疗慢性进展性IgA肾病（IgAN）的疗效及安全性.方法：回顾性分析2009年6月~2012年7月在我院确诊为IgAN患者,Lee氏分级Ⅱ级或以上,并应用激素分别联合CTX或LEF治疗的患者57例,CTX组25例,LEF组32例;收集患者治疗前及每月随访资料.结果：经治疗IgAN尿蛋白总缓解率达87.7%,治疗期间CTX组和LEF组尿蛋白部分缓解分别为7例（28.0%）和11例（34.4%）,P=0.607;CTX组和LEF组尿蛋白完全缓解分别为14例（56.0%）和18例（56.2%）,P=0.985.CTX组和LEF组部分缓解时间分别为（2.95±1.70）月和 （3.27±3.01）月,差异有统计学意义（P=0.048）,CTX组和LEF组尿蛋白完全缓解时间分别为（5.45±3.31）月和（6.69±5.82）月,P=0.052.随访中CTX组副反应发生率12.0%,LEF组副反应发生率6.25%.结论：激素联合CTX或LEF治疗慢性进展性IgAN均有相同的疗效,CTX组部分缓解时间较LEF快,长期疗效及安全性有待进一步观察.     

The efficacy and safety of tacrolimus monotherapy in adult-onset nephrotic syndrome caused by idiopathic membranous nephropathy

Introduction: The purpose of the study is to evaluate the efficiency and safety of tacrolimus (TAC) monotherapy in the treatment of nephrotic idiopathic membranous nephropathy (IMN) compared with the protocol of cyclophosphamide (CTX) combined with corticosteroids.

Methods: In total, 58 patients with nephrotic syndrome and biopsy-proven IMN were included in this study. 30 patients received TAC monotherapy with an initial dose of 0.05–0.1?mg/kg/day. 28 patients received transvenous CTX at a dose of 0.5–0.75?g/m² once in every month initially for 6?months and once in every 2 or 3?months for the later period, and the regimen was combined with corticosteroids (prednisone 1?mg/kg/d). All patients were observed for the treatment effects, recurrence and side effects.

Results: Twelve months after the initial treatment, a total of 24 (80%) patients in the TAC group and 23 (82.1%) patients in the CTX group achieved remission (either partial or complete remission). The survival curve of the probability of remission and complete remission were similar between the two groups (p?>?.05). Proteinuria (based on 24?h urinary protein excretion) was significantly decreased, and serum albumin was significantly increased after immunosuppressive treatment in both the groups. Estimated glomerular filtration rate (eGFR) was comparable between before and after treatment. The main adverse effects in TAC treatment were glucose intolerance, diabetes and abnormal aminotransferase.

Conclusions: TAC monotherapy is an alternative therapeutic regimen for patients with nephrotic IMN. Its short-term efficiency and patient tolerance are both acceptable.     

Leflunomide plus low-dose prednisone in patients with progressive IgA nephropathy: a multicenter,prospective, randomized,open-labeled,and controlled trial

BackgroundImmunoglobulin A nephropathy (IgAN) is the most common cause of glomerulonephritis worldwide, and the optimal approach to its treatment remains a significant challenge.MethodsWe did a prospective, randomized, open-labeled, multicenter, controlled trial, comprised of 3-month run-in, 12-month treatment, and 12-month follow-up phases. After 3-month run-in phase, patients with biopsy-confirmed IgAN at risk of progression were randomly allocated to LEF plus low-dose prednisone (LEF + prednisone group) or conventionally accepted-dose prednisone [prednisone(alone) group] Our primary outcome was 24-h urine protein excretion (UPE) and secondary outcomes were serum albumin (sALB), serum creatinine (Scr), and eGFR. Safety was evaluated in all patients who received the trial medications.ResultsOne hundred and eight patients [59 in LEF + prednisone group, 49 in prednisone (alone) group]were enrolled and finished their treatment and follow-up periods. There is no significant difference in the baseline level between the two groups. Compared with baseline, both groups showed a significant decrease in 24-h UPE (p < 0.01) and increase in sALB (p < 0.01), with stable Scr and eGFR throughout the 12-month treatment period. What’s more, these effects were sustained through the 12-month follow-up period. However, there was no difference in 24-h UPE, sALB, Scr, and eGFR between the two groups (p > 0.05). At 12 months, a difference in overall response rate, relapsing rate, and incidence of adverse events between the two groups was not significant.ConclusionsThe efficacy and safety of LEF plus low-dose prednisone and conventionally accepted-dose prednisone in the treatment of progressive IgAN are comparable.     

Effects of mycophenolate mofetil and glucocorticoid on Henoch-Schonlein purpura nephritis in children

Objective To explore the effect and safety of mycophenolate mofetil (MMF) and glucocorticoid on Henoch-Schonlein purpura nephritis in children and compared with cyclophosphamide (CTX). Methods The data of 48 patients diagnosed as Henoch-Schonlein purpura by renal biopsy were retrospectively analyzed. Median follow-up time was 22(7, 48) months. The subjects were divided into 2 groups. 34 cases were in the MMF group: MMF (15-20 mg?kg-1?d-1 or 800-1200 mg/m2)+ prednisone, and 14 cases in the CTX group: CTX (8 - 12 mg?kg-1?d-1)+prednisone. Clinical and laboratory data were collected at baseline and 1, 3, 6 months after treatment. During follow - up, cumulative retreatment rate and adverse reactions after treatment were recorded. Results In two groups after treatment for 1, 3, 6 months, 24 hours urinary protein quantitative was significantly lower than the baseline value, serum albumin (sAlb) was significantly higher than the baseline value, and serum creatinine (Scr) indicated no statistically significant difference during the follow-up period. After the treatment of 1 month, the efficient rate of MMF group was higher than the CTX group (MMF 73.5 % vs 42.9%, P=0.046), the effective treatment of 3, 6 months at the end of the follow-up, no statistically significant difference were observed in the accumulative remission rate. The total rate of retreatment was 10.4% (5/48), where MMF group was lower that of the than CTX group (3.0% vs 28.6%, P＜ 0.001). The retreatment often occurred after discontinuation of prednisone and CTX, MMF reduction process. Eleven children received IMPDH2 gene polymorphisms test in MMF group, 9 AA children had shorter time for drugs to be effective than that of the AG and GG children. The incidence of adverse reactions of MMF group was obviously lower than CTX group at the end of the follow-up (8.8% vs 35.7%, P=0.025), where two groups developed fungal infection. Conclusions The short-term effect of both groups are the same, but the recurrent rate and incidence of adverse reactions of MMF group are lower than those of the CTX group. The preliminary study shows that IMPDH2 gene polymorphisms is associated with MMF curative effect and adverse reactions.     

来氟米特对Ⅳ型及Ⅴ型狼疮肾炎的诱导维持治疗

目的 观察来氟米特诱导和维持治疗Ⅳ型及Ⅴ型狼疮肾炎（LN）的疗效及安全性。方法 单中心前瞻性临床研究。选取1个月内经病理证实的Ⅳ型及Ⅴ型狼疮肾炎患者，在使用激素的基础上随机入组分别使用来氟米特(口服30 mg/d，LEF组)或环磷酰胺（静1 g/月，CTX组）。6个月后，维持方案为LEF组续用LEF 20 mg/d，CTX组续用CTX 1 g/3月，两组泼尼松均使用5~10 mg/d。评价治疗的安全性和有效性。结果 共40例患者进入试验，其中LEF组19例，CTX组21例；LEF组17例、CTX组18例完成了诱导期治疗。LEF组诱导治疗总有效率达88.2％，完全缓解率为52.9％；CXT组治疗总有效率为72.2％，完全缓解率为44.4％；两组间差异无统计学意义。缓解的患者中，LEF组有7例进入维持期治疗，随访时间（18.6±6.5）月，未出现蛋白尿复发，其中3例进行了重复肾活检，结果显示肾脏病理类型均由重转轻，活动性指数下降，但慢性指数有所上升。CTX组有11例进入维持期治疗，随访时间（25.1±9.6）月，其中有3例在随访中蛋白尿复发。LEF组发生不良反应14例次，主要是感染，以带状疱疹多见。环磷酰胺组发生不良反应18例次，主要为感染和月经不调，组间比较差异无统计学意义。结论 来氟米特联合激素诱导及维持治疗Ⅳ型及Ⅴ型LN疗效显著，患者耐受性良好。     

来氟米特联合糖皮质激素治疗IgA肾病的临床研究

目的 观察应用来氟米特（Leflunomide,LEF）联合激素治疗IgA肾病的疗效和安全性.方法 选择IgA肾病患者63例,分为LEF合并激素治疗组（LEF组）及大剂量激素治疗组（激素组）,观察治疗前和治疗6个月、12个月后的24 h尿蛋白定量、血清白蛋白、肾小球率过滤（eGFR）、收缩压、舒张压等实验室指标的变化,并进行疗效评价.结果 LEF组和激素组治疗6个月和12个月后的24 h尿蛋白定量、收缩压、舒张压均较治疗前显著下降（P＜0.05）,血清白蛋白水平较治疗前显著升高（P＜0.05）,2组eGFR变化均无统计学差异（P＞0.05）.治疗12个月后LEF组的总有效率明显高于激素组（P＜0.05）,而完全缓解率和部分缓解率的差异无统计学意义（P＞0.05）,2组不良反应无显著性差异（P＞0.05）.结论 LEF联合激素可以作为治疗IgA肾病的选择之一,且安全、有效.     

Effects of the angiotensin II type 1 receptor antagonist candesartan,compared with angiotensin-converting enzyme inhibitors,on the urinary excretion of albumin and type IV collagen in patients with diabetic nephropathy

Background. We previously reported that the angiotensin II type 1 receptor antagonist candesartan was effective in reducing blood pressure and microalbuminuria in hypertensive patients with diabetic nephropathy after angiotensin-converting enzyme (ACE) inhibitors were replaced due to side effects. In the present study, the clinical effects of candesartan were investigated and compared with ACE inhibitors in patients with stage 2 or 3A diabetic nephropathy, mainly with respect to the effects on the urinary excretion of albumin and type IV collagen. Methods. Forty-nine patients (26 males/23 females) with diabetic nephropathy (stage 2 or 3A), including normotensive patients, were the study subjects. The patients were treated with either an ACE inhibitor (23 patients) or candesartan (26 patients) for 11 ± 3 months. The urinary excretion of albumin and urinary type IV collagen was measured. Results. Posttreatment blood pressure tended to decrease, but such a decrease did not reach a statistically significant level, nor did it show any intergroup difference. The urinary albumin excretion was positively correlated with pretreatment mean blood pressure and left ventricular mass index, but the urinary type IV collagen excretion did not show such correlations. The urinary albumin excretion decreased significantly after treatment to a similar extent in both groups, whereas the urinary type IV collagen excretion decreased significantly only in the candesartan group. Conclusion. It was revealed that ACE inhibitors and candesartan reduced urinary albumin excretion to a similar extent in patients with diabetic nephropathy. From the results of the present study, it is inferred that the renoprotective effect of candesartan in diabetic nephropathy may partially differ from that of ACE inhibitors.     

小剂量环孢素A联合小剂量泼尼松治疗特发性膜性肾病的初步观察

目的 非随机前瞻性观察小剂量环孢素A（CsA）联合小剂量泼尼松在我国特发性膜性肾病治疗中的疗效及不良反应,比较其与环磷酰胺（CTX）联合足量泼尼松的异同。 方法 31例经肾活检病理证实为特发性膜性肾病（Ⅰ~Ⅲ期）的肾功能正常的大量蛋白尿患者纳入本研究。CTX组20例,100 mg/d, 累积量约8 g;口服泼尼松0.6~1.0 mg&#8226;kg-1&#8226;d-1,2～3个月后逐渐减量。CsA 组19例（包括CTX组中治疗无效或复发的8例）,起始量1.0~1.5 mg&#8226;kg-1&#8226;d-1,2～3个月无效者,逐渐加量,最大剂量≤2.5 mg&#8226;kg-1&#8226;d-1;口服泼尼松0.15~0.50 mg&#8226;kg-1&#8226;d-1,3月个后逐渐减量。观察两组治疗前后的尿蛋白、血白蛋白和血肌酐等疗效指标及不良反应。 结果 CTX组随访（48±22）周,13例有效(65%,7例部分缓解,6例完全缓解),7例无效(35%)。CsA组随访（44±15）周,其中2例因不良反应而退出,余17例中,12例有效(70%,6例部分缓解,6例完全缓解),5例无效(30%)。两组缓解比例的差异无统计学意义。CTX组的不良反应有肝功能损伤等。CsA组的不良反应有血肌酐上升（3例）、高血压（12例）等,停药后或用药可控制。 结论 小剂量CsA联合小剂量泼尼松与CTX联合足量泼尼松治疗特发膜性肾病的缓解比例相近,对于CTX治疗无效或复发的患者,仍可能有效,虽然不良反应较多,但易于监测和控制。     

肾安冲剂对阿霉素肾病大鼠的治疗作用

目的：观察肾安冲剂对阿霉素肾病大鼠的治疗作用。方法：SD大鼠尾静脉注射阿霉素建立肾病综合征模型。雄性SD大鼠72只,随机分为6组：正常对照组、模型组、肾安冲剂小剂量组、肾安冲剂中剂量组、肾安冲剂大剂量组和泼尼松组,每组12只。连续给药8周,观察肾安冲剂对阿霉素肾病大鼠的24h尿蛋白、血清白蛋白、血清胆固醇、三酰甘油及肾组织病理形态学等方面的影响。结果：（1）与正常组比较,模型组24h尿蛋白定量、血脂水平明显升高,血清白蛋白水平明显降低（均P〈0.01）;（2）与模型组比较,各治疗组大鼠24h尿蛋白定量、血脂水平明显降低,血清白蛋白水平明显升高（均P〈0.01）;（3）肾安冲剂治疗组各指标与泼尼松组比较均有统计学差异（均P〈0.01）,说明肾安冲剂疗效优于泼尼松。结论：肾安冲剂具有降低尿蛋白、升高血清白蛋白水平,降低血脂以及减轻肾脏损害的作用。     

来氟米特与环磷酰胺治疗膜性肾病的疗效比较

目的：评价来氟米特（LEF）与环磷酰胺（CTX）分别联合泼尼松（PED）治疗成年人特发性膜性肾病（IMN）的疗效及安全性。方法：80例原发性肾病综合征患者经肾活检确诊为IMN,在诊断上排除了继发性膜性肾病,随机分两组：LEF组40例采用LEF＋PED治疗,CTX组40例采用CTX＋PED治疗。治疗期间及治疗前后,监测血常规、尿常规、24h尿蛋白定量、血白蛋白、血脂、肝肾功能,6个月后行疗效和安全性的评价。结果：（1）LEF组40例中失访1例,完成6个月治疗39例。CTX组40例中因不耐受药物不良反应中途退出7例,完成6个月治疗33例;（2）治疗3个月后LEF组的完全缓解率显著低于CTX组（χ2=4.3516,P〈0.05）,LEF组的未缓解显著高于CTX组（χ2=4.9059,P〈0.05）;治疗6个月后两组的完全缓解率、未缓解率差异无统计学意义（P均〉0.05）;（3）治疗6个月后,两组患者的24hUpro、Alb、TC、TG均较治疗前显著改善（LEF组：t=7.0841,9.0998,8.4412,7.7942;CTX组：t=8.7823,9.2826,7.1252,6.9731,P均〈0.01）,CTX组的改善略微优于LEF组（t=1.8112,1.6780,0.9881,1.6778,P均〉0.05）,但差异均无统计学意义;（4）CTX组中因不良反应中途退出的比率（7/40）显著高于LEF组（0/40）,（χ2=5.6360,P〈0.05）;LEF组不良反应发生率（5/39）显著低于CTX组（13/40）,（χ2=4.3468,P〈0.05）,差异均有统计学意义。结论：来氟米特治疗膜性肾病,与环磷酰胺的临床疗效相似,不良反应较少,但起效稍慢。     

Safety and efficacy of mizoribine treatment in nephrotic syndrome complicated with hepatitis B virus infection: a clinical study

Objective The objective of this study is to explore the efficacy and safety of mizoribine (MZR) in treating nephrotic syndrome patients afflicted with hepatitis B virus (HBV). Methods The present study included 36 nephrotic syndrome patients accompanied with HBV infection. A draft of MZR (150–200?mg/d), methylprednisolone (0.6–0.8?mg/kg·d), and entecavir (0.5?mg/d) was administered to study patients over 24 weeks. The serum albumin (AlB), 24-h urine protein (24-U-TP), liver and renal functions, and HBV-DNA were quantified before and at 2, 4, 8, 12, 16, 20, and 24 weeks after the treatment. The adverse responses were recorded. Results The AlB levels of patients increased gradually after comprehensive treatment, while the 24-U-TP, serum cholesterol, and triglyceride (TG) levels declined gradually. The changes at 24 weeks post-treatment were statistically significant. Compared with the levels before treatment, the HBV-DNA, transaminase, and renal functions of the patients were not significantly altered after the treatment. No evident adverse response was found. Conclusion Treatment using MZR in combination with methylprednisolone and entecavir in HBV-positive nephrotic syndrome patients displays significant efficacy with a low incidence of adverse reactions.     

加减地龙活血汤联合激素治疗原发性肾病综合征

目的探讨加减地龙活血汤治疗原发性肾病综合征的临床疗效。方法将病理表现为系膜增生性肾小球肾炎（MsPNS）的原发性肾病综合征患者96例随机分为A、B、C组,各32例。A组用泼尼松和（或）环磷酰胺（CTX）联合地龙活血汤和相应时间的辨证中药;B组除不用地龙活血汤,其余治疗方法同A组;C组仅用泼尼松和（或）CTX治疗。比较3组治疗前以及治疗后第6、12个月24h尿蛋白定量、总胆固醇（TC）、三酰甘油（TG）、血浆白蛋白（Alb）、血红蛋白（Hb）、D二聚体及尿纤维蛋白降解产物（UFDP）等,并比较各组转归与疗效、复发情况和不良反应。结果A组总有效率高于B、C组（P〈0．05或P〈0．01）。3组治疗6个月后复发率无差异（P〉0．05）;治疗12个月后,A、B、C组复发率依次升高（P〈0．05）。A、B组阴虚火旺症、Cushing综合征与感染发生率较C组低;B、C组血栓形成发生率较A组高（Pd0．05）。结论泼尼松和（或）CTX联合地龙活血汤可增强肾病综合征患者疗效,而且可减低复发和不良反应的发生。     

中西医结合治疗成人难治性肾病综合征的荟萃分析

目的评价中西医结合治疗成人原发性难治性肾病综合征（RNS）的临床疗效以及不良反应。方法采用荟萃（Meta）分析的方法,对近12年中西医结合治疗成人RNS的随机对照研究（RCT）进行系统评价。采用电子检索Medline、中国生物医学文献数据库（CBMdisk）、万方数据库、西文生物医学期刊文献数据库（EMCC）,并手工检索近6个月中西医结合杂志和国内肾脏疾病相关杂志的8种核心期刊;提取和比较中西医结合治疗成人RNS患者的RCT的数据;采用Cochrane协作网专用软件RavMan4．2进行统计分析。结果检索符合纳入标准的RCT研究13篇,共777例患者。Meta分析显示中西医结合治疗对成人RNS的治疗与同期平行随机对照的西药治疗组相比较,显示更好的临床疗效,降低24h尿蛋白定量及总胆固醇水平、提高血浆白蛋白水平;同时也降低不良反应的发生率。结论中西医结合治疗RNS与单独使用泼尼松、环磷酰胺等西药相比较,临床疗效明显提高、不良反应减少。     

Effect of fosinopril in children with steroid-resistant idiopathic nephrotic syndrome

We aimed to test if fosinopril reduces urinary protein excretion and alleviates renal tubular damage in normotensive children with steroid-resistant idiopathic nephrotic syndrome (SRINS). We also aimed to evaluate whether there are changes in steady-state blood pressure and serum concentrations of serum angiotensin-converting enzyme (ACE) and plasma renin activity or angiotensin II (AT-II) in children under this treatment. Forty-five normotensive patients with SRINS were randomly divided into two groups. Group I was treated with fosinopril and prednisone for 12 weeks, while group II was treated with prednisone alone for the same duration. The values of 24-h urinary protein excretion were 1.25±0.64 vs 2.52±0.56 g/24 h (P<0.05), 1.16±0.45 vs 2.42±0.24 g/24 h (P<0.05), and 1.10±0.41 vs 2.05±0.46 g/24 h (P<0.05) in group I and group II patients, respectively, at 4, 8, and 12 weeks. Patients in group I showed lower serum concentrations of urinary retinol-binding protein and β₂-microglobulin (P<0.01) at the end of the study, but the patients’ blood pressure and components of the renin-angiotensin system (RAS) had no change during treatment. The result suggested that fosinopril significantly reduced proteinuria and alleviated renal tubular damage, but did not influence blood pressure and components of systemic RAS in normotensive children with SRINS.     

环孢素A联合激素治疗难治性肾病综合征31例临床疗效观察

目的 探讨环孢素A（cyclosporine-A,CsA）联合激素治疗难治性肾病综合征的临床疗效及安全性.方法 对31例难治性肾病综合征患者使用糖皮质激素联合CsA治疗：CsA起始剂量平均（1.57±0.25）mg·kg^-1 ·d^-1,泼尼松起始剂量平均（0.69±0.20）mg· kg^-1·d^-1,分别测定CsA治疗前及治疗后1、3、6个月患者的24 h尿蛋白定量、肝功能[丙氨酸氨基转移酶（glutamate-pyruvate transaminase,AST）、天冬胺酸氨基转移酶（glutamic oxalacetic transaminase,ALT）、血浆白蛋白（serum albumin,Alb）]、肾功能[血肌酐（serum creatinine,SCr）、血尿酸（uric acid,UA）]、血常规[白细胞（white blood corpuscle,WBC）、血红蛋白（hemoglobin,Hb）、血小板（blood platelet,PLT）]及环孢素血药浓度等指标的变化,并记录不良反应.结果 加用CsA治疗后患者各项指标均较治疗前明显好转,治疗3个月时24 h尿蛋白定量由治疗前的（5.56±2.13）g降至（1.37±1.41） g（P＜0.05）,血浆白蛋白由（24.80±4.69） g/L升至（37.5±5.03） g/L（P＜0.05）,完全缓解9例,部分缓解12例,缓解率67.7％;治疗6个月时24 h尿蛋白定量由治疗前的（5.56±2.13）g降至（0.83±1.21）g（P＜0.05）,血浆白蛋白由（24.80±4.69） g/L升至（41.08±5.64） g/L（P＜0.05）,完全缓解16例,部分缓解11例,无效4例,缓解率87.1％,治疗前后结果差异有统计学意义（P＜0.05）.结论 CsA联合激素治疗可显著减少肾病综合征患者的尿蛋白,且不良反应少,可用于难治性肾病综合征的治疗.     

Safety and efficacy of fluvastatin in hyperlipidemic patients with chronic renal disease

BACKGROUND: There are few reports on the safety and efficacy of long-term treatment with statins in patients with chronic renal disease and hyperlipidemia. We evaluated these subjects treated with fluvastatin. METHODS: After a 4-week run-in period, a total of 80 patients with diabetic nephropathy or chronic glomerulonephritis were randomly allocated to receive dietary therapy and fluvastatin 20 mg/day (n=39), or dietary therapy alone (n=41) for a period of 48 weeks. Lipid parameters, rhabdomyolysis-related indicators, 24-hour urinary albumin excretion and creatinine clearance were measured. The pharmacokinetics of fluvastatin was examined in 8 patients. RESULTS: Creatinine clearance and 24-hour urinary albumin excretion did not differ between the two groups. The peak serum fluvastatin concentration (Cmax) was 141+/-67 microg/L and the mean AUC0-6 h was 341+/-149 microgh/L. Fluvastatin treatment significantly lowered serum total cholesterol, low-density lipoprotein (LDL) cholesterol and apo-lipoprotein B concentrations by 16%, 25%, and 22%, respectively, compared with patients receiving dietary therapy alone. There were no significant differences in serum triglyceride and high-density lipoprotein (HDL) cholesterol concentrations between the two treatment groups. Serum creatine kinase and aldolase concentrations did not change throughout treatment in both groups. CONCLUSIONS: Fluvastatin treatment significantly improved lipid parameters in patients with chronic renal disease. Fluvastatin was well tolerated, with no adverse effects on renal function and no muscular toxicity. However, the drug showed no direct renoprotective effects.     

The effect of amiloride in decreasing albuminuria in patients with diabetic kidney diseases: a prospective,crossover, open-label study

BackgroundDiabetic kidney diseases (DKD) were the leading cause of End-stage renal diseases worldwide. Albuminuria was a target for treatment in DKD and decreasing albuminuria was particularly important for improving its prognosis. However, there is still a lack of specific treatment for DKD.MethodsWe conducted a prospective, crossover, open-label study to investigate the effect of amiloride in patients with DKD. Safety and efficacy were assessed by monitoring urine protein creatinine ratio(uPCR), urinary albumin creatinine ratio (uACR), blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid, serum soluble urokinase-type plasminogen activator receptor (suPAR) and urinary suPAR. Ten subjects were enrolled in the trial.ResultsIn this prospective, crossover, open-label design, amiloride could induce a significant decrease of uACR in DKD. The decrease of serum and urinary suPAR in the amiloride/hydrochlorothiazide (HCTZ) group was also significant compared with those patients using HCTZ as the control group. Correlation analysis showed that the levels of urinary suPAR were positively associated with uPCR and uACR. No significant difference in blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid was seen between the amiloride/HCTZ group and the control group.ConclusionIn summary, among patients with DKD, amiloride could decrease albuminuria without severe side effects, which was accompanied by the significant decline of urinary suPAR.     

环孢霉素A与环磷酰胺联合激素治疗膜性肾病的疗效比较

目的：比较环孢霉素A（CSA）与环磷酰胺（CTX）联合激素治疗成年人特发性膜性肾病（IMN）的疗效和安全性。方法：76例原发性肾病综合征患者经肾活检确诊为IMN,在诊断上排除了继发性膜性肾病,单用激素治疗无效或复发,随机分两组分别予CSA联用糖皮质激素治疗（CSA组）或CTX联用糖皮质激素治疗（CTX组）,疗程至少12个月。观察各组的24h尿蛋白定量、血浆白蛋白、肾功能、血糖、白细胞总数及其不良反应,以及治疗前后的完全缓解率、部分缓解率。全部患者且在正式进入研究治疗前未用或已停用类固醇激素和细胞毒药物达半年以上。结果：治疗3个月末,CsA组的24h尿蛋白、胆固醇、三酰甘油显著低于CTX组（P均〈0.01）,血清白蛋白显著高于CTX组（P〈0.01）。两组患者的血肌酐比较差异无统计学意义（P〉0.05）,而CTX组的WBC显著低于CsA组（P〈0.01）。CsA组完全缓解率显著高于CTX组（χ2=4.6317,P〈0.05）。治疗12个月末两组的完全缓解率差异无统计学意义（χ2=1.2575,P〉0.05）。CsA组的不良反应发生率（8/40=20.0%）显著低于CTX组（15/36=41.7%）（χ2=4.2146,P〈0.05）。结论：与CTX相比,CsA联用糖皮质激素对IMN治疗12个月的总体疗效相当,但CsA起效更快,近期疗效更好,不良反应更小。CsA≤5mg.kg-1.d-1用于肾功能正常IMN患者是安全有效的。     

An oral cathepsin K inhibitor ONO-5334 inhibits N-terminal and C-terminal collagen crosslinks in serum and urine at similar plasma concentrations in postmenopausal women

Relationships between the plasma concentration of a cathepsin K inhibitor (ONO-5334) and inhibition of bone resorption markers N-telopeptide of type I collagen (NTX) and C-telopeptide of type I collagen (CTX) in serum and urinary NTX/creatinine and CTX/creatinine were examined in 10 postmenopausal women. The subjects received slow-release tablets of 100 mg ONO-5534 under fasted or fed conditions in a study with a crossover design. Inhibition of serum NTX and CTX levels and plasma concentrations of ONO-5334 were monitored at 0, 24, 48 and 168 h after dosing. Changes in urinary NTX/creatinine and CTX/creatinine levels in second morning urine were evaluated on 0, 1, 2 and 7 days after dosing. Data were analyzed using sigmoid maximal drug effect (E_max) models. The maximal inhibition, estimated E_max values, were − 31.8% for serum NTX, − 53.1% for serum CTX, − 67.2% for urinary NTX/creatinine, and − 95.2% for urinary CTX/creatinine. The estimated half maximal effective plasma concentrations (EC₅₀) of ONO-5334 and confidence intervals were 1.79 (1.01 to 3.16) ng/mL for serum NTX, 2.07 (1.63 to 2.62) ng/mL for serum CTX, 1.85 (1.30 to 2.61) ng/mL for urinary NTX/creatinine, and 1.98 (0.94 to 3.76) ng/mL for urinary CTX/creatinine. EC₅₀ values for the four crosslinks did not significantly differ, as indicated by the overlapping 95% confidence intervals. The highest signal-to-noise ratio was achieved with serum CTX, and was 2-fold higher than that on serum NTX. Inhibition for serum NTX and CTX, and urinary NTX/creatinine and CTX/creatinine by ONO-5334 were all correlated with correlation coefficients ranging from 0.55 to 0.80. In conclusion, data of ONO-5334 slow-releasing tablets in postmenopausal women were well fitted in E_max model. In all measured telopeptides, the maximal inhibition was obtained at urinary CTX/creatinine level, but serum CTX had the highest signal-to-noise ratio. Inhibition for all measured telopeptides by ONO-5334 were all correlated. The estimated half maximal effective plasma concentrations were not significantly different between all measured telopeptides.     

中西医结合治疗狼疮性肾炎疗效观察

目的：评估中西医结合治疗狼疮性肾炎(LN)的疗效和副作用，旨在进一步手求对狼疮性肾炎副作用小、完全缓解率高、复发率低的治疗方案。方法：46例LN患随机分为两组，单纯激素组(20例)：单纯选用强的松标准疗程；联合治疗组(26例)：环磷酰胺(CTX)冲击 激素标准疗程 中药治疗。根据中医对LN的分型进行辨证施治。中药治疗对CTX冲击与大量激素法疗研产生的不良反应针对性用药。同时对肾袁竭、血液高凝状态给予血透、抗凝对症治疗。结果：单纯激素组完全缓解率为55．55％，总有效率为80％。联合治疗组完全缓解率为73．07％，总有效率为92％。5年复发率比较，单纯激素组为25％，联合治疗组为15.3％。结论：从完全缓解率、总有效率、复发率及不良反应几方面分析研究表明，联合方案治疗LN明显优于单用激素。加用中药可保证CTX冲击与激素等主要用药的顺利实施，减少不良反应，提高缓解率，降低复发率。