Probucol for treatment of hyperlipidemia in persistent childhood nephrotic syndrome

 In a prospective, uncontrolled multicenter study, we have evaluated the effects of probucol on hyperlipidemia, proteinuria, and glomerular filtration rate (GFR) in hyperlipidemic children with persistent nephrotic syndrome. Probucol was started for a total of 12 weeks in 8 children and for 24 weeks in 14 children. Lipoprotein profiles, serum malondialdehyde (MDA) levels, proteinuria, renal function, and electrocardiogram were monitored every 4 weeks. Side effects were recorded by questionnaire. Treatment was completed by 7 of 8 patients for 12 weeks and by 7 of 14 children for 24 weeks. After 12 weeks, the mean serum concentrations of triglycerides (−15%), total cholesterol (−25%), very low-density lipoprotein-cholesterol (−27%), low-density lipoprotein-cholesterol (−23%), and high-density lipoprotein-cholesterol (−24%), as well as apolipoprotein (apo) A-I (−19%), apo B (−21%), and MDA (−32%) were reduced. The positive effects of probucol on the lipoprotein profile persisted over 24 weeks; however, there was no significant effect on either proteinuria or GFR. In conclusion, probucol had beneficial effects on lipoproteins and lipid peroxidation, but improved neither proteinuria nor GFR. The drug was generally tolerated well, but had to be discontinued because of a prolonged QT interval in 4 of 22 patients. Received: 17 November 1997 / Revised: 12 June 1998 / Accepted: 18 June 1998     

Lovastatin in the treatment of hypercholesterolemia in nephrotic syndrome due to diabetic nephropathy stage IV-V.

The efficacy and safety of lovastatin, a drug for lowering hypercholesterolemia, have been evaluated in ten adult patients with insulin-dependent diabetes mellitus (IDDM) and nephrotic syndrome due to diabetic nephropathy stage IV or V of Mogensen. For the first 8 weeks the patients received only a sugar-free isocaloric diet of which fats supplied approximately 30% of the total caloric intake and with not more than 300 mg cholesterol daily. After this run-in period patients were treated with 20 mg lovastatin once daily for 12 weeks while receiving the same isocaloric diet as previously. Body weights and glycosylated hemoglobin concentrations (HbAlc) did not change significantly during this period. The baseline plasma cholesterol concentrations (mean +/- SD) decreased only by 2% (from 310 +/- 54 to 303 +/- 46 mg/dl) during the 8 weeks with low cholesterol diet and by 25% (from 303 +/- 46 to 228 +/- 38 mg/dl) during the 12-week period on lovastatin therapy (p less than 0.005). The mean concentrations of low-density lipoprotein (LDL-)-cholesterol decreased by 3% (from 218 +/- 53 to 211 +/- 52 mg/dl) during the diet period and by 35% (from 211 +/- 52 to 137 +/- 38 mg/dl) during the period with lovastatin therapy (p less than 0.001). Concentrations of high-density lipoprotein (HDL) cholesterol increased slightly (11%) during the therapy with lovastatin (NS). Baseline plasma triglycerides fell by 22% (from 188 +/- 97 to 146 +/- 59 mg/dl) during the period with fat-restriction (p less than 0.05) and by 13% (from 146 +/- 59 to 127 +/- 54 mg/dl) during the period of lovastatin therapy (NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

通心络治疗肾病综合征高脂血症

目的观察通心络胶囊治疗肾病综合征（NS）患者高脂血症的临床疗效。方法将NS高脂血症并血粘度异常者57例分为2组,治疗组30例,对照组27例。治疗组给予通心络胶囊每天9粒（0．38克／粒）,分3次口服,辛伐他汀20mg／d,睡前顿服,对照组患者仅服用辛伐他汀20mg／d,睡前顿服,共治疗30d。分别于给药前的3d内和疗程结束后的3d内检测2组患者血总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDDC）、高密度脂蛋白胆固醇（HDDC）和血粘度（全血比粘度、血浆比粘度）。结果2组患者治疗后TC、TG、LDL-C均较治疗前下降,HDL-C均较治疗前升高,全血比粘度、血浆比粘度均较治疗前下降,差异有统计学意义（P〈0．05）;治疗组治疗后TC、TO、LDL-C均较对照组治疗后低,HDLC较对照组治疗后高,全血比粘度、血浆比粘度均较对照组治疗后低,差异有统计学意义（P〈0．05）。结论联用通心络与辛伐他汀能更有效的改善血脂异常和高血粘度。     

低分子肝素联合激素、环磷酰胺治疗难治性肾病综合征的Meta分析

目的评价低分子肝素联合激素、环磷酰胺治疗难治性肾病综合征(refractory nephrotic syndrome,RNS)的疗效。方法电子检索知网、万方、维普、PubMed、EMbase和Cochrane Library数据库,检索时间均从建库至2018年3月,收集低分子肝素联合激素、环磷酰胺治疗RNS的临床随机对照试验(randomized controlled trials,RCT),根据纳入和排除标准筛选文献、质量评价及数据提取后,采用Revman5.3软件进行Meta分析。结果共纳入15篇中文RCT研究,1077例RNS患者,其中试验组542例,对照组535例。Meta分析结果显示,试验组完全缓解率[OR=2.28,95%CI(1.76,2.95),P<0.00001]明显高于对照组,同时实验组24 h尿蛋白定量[MD=-1.14,95%CI(-1.57,-0.72),P<0.00001]、血肌酐[MD=-7.81,95%CI(-8.87,-6.75),P<0.00001]、尿素氮[MD=-1.81,95%CI(-1.88,-1.74),P<0.00001]均明显优于对照组。结论对于我国RNS患者,低分子肝素联合激素、环磷酰胺治疗疗效显著,但仍需要更多高质量的RCT进一步证实。     

Effect of probucol on hyperlipidemia in patients with nephrotic syndrome

We have evaluated the effect of the antihyperlipidemic agent probucol on hyperlipidemia in patients with nephrotic syndrome. Twelve patients with long-standing nephrotic syndrome received 500 mg of probucol daily for 12 weeks. Serum total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol were significantly lowered with probucol treatment. There were no differences in urine protein, serum total protein, serum albumin and renal function before and after probucol treatment. No drug-related side effects were observed during our study. These results indicated that probucol was effective against hyperlipidemia and free from side effects in patients with persistent nephrotic syndrome. The use of probucol is therefore suggested to be advisable when antihyperlipidemic treatment is required in some subgroups of nephrotic syndrome.     

Anti-oxidant status in relation to lipoproteins, leptin and pro-inflammatory cytokines in children with steroid-sensitive nephrotic syndrome

BACKGROUND: Reactive oxygen species and cytokines are reported to play a role in the proteinuria of nephrotic syndrome. The aim of this study was to investigate indirect evidence of oxidant activity together with leptin, lipoproteins and pro-inflammatory cytokines in children with steroid-sensitive nephrotic syndrome. METHODS: A total of 40 children with steroid-sensitive nephrotic syndrome (20 with newly onset or relapse comprised group I and 20 in remission while receiving steroids comprised group II) and 20 sex and age matched healthy control children were included. The following indirect parameters of oxidant activity were determined: serum malondialdehyde, erythrocyte superoxide dismutase, catalase and whole-blood-reduced glutathione. Serum leptin, lipids and lipoproteins were also determined. RESULTS: Similar glutathione, increased malondialdehyde levels and decreased superoxide dismutase and catalase activity were observed in group I patients compared with controls. There was no significant difference in these variables between group I and group II (P >0.05). Tumour necrosis factor-alpha and interleukin-6 concentrations were similar in patients and controls. Concentrations of interleukin-1beta and interleukin-8 were higher in the active phase of nephrotics compared with controls (P <0.05). Significant positive correlations were found between malondialdehyde and interleukin-1beta, interleukin-6, leptin and lipoprotein (a) (P <0.05). There were significant negative correlations between anti-oxidants and leptin, lipoprotein (a) and several cytokines (P <0.05). CONCLUSIONS: Changes in the concentrations of malondialdehyde, superoxide dismutase, catalase and glutathione are compatible with increased amounts of oxidation in steroid-sensitive nephrotic syndrome. Leptin and pro-inflammatory cytokines may be related to excessive protein permeability in nephrotic syndrome.     

Efficacy of leflunomide combined with prednisone in the treatment of refractory nephrotic syndrome

Objective: To assess the safety and clinical efficacy of leflunomide (LEF) and prednisone on refractory nephrotic syndrome (RNS).

Methods: A total of 52 patients with RNS were treated for 24 weeks between 2010 and 2014 in our hospital. In the treated group, 26 patients were treated with LEF and prednisone, and, in the control group, 26 patients were treated with cyclophosphamide (CTX) and prednisone. During the treatment, 24?h urinary protein excretion and the serum levels of albumin and cholesterol, and kidney function were assayed before and after the therapy. Adverse reactions during treatment were recorded.

Results: In the LEF group, the medication was markedly effective in eight cases and effective in nine cases; the total efficacy rate was 65.30%. In the CTX group, the treatment was markedly effective in six cases and effective in nine cases; the total efficacy rate was 57%. There were no significant differences between the results of the total efficacy rate (p?>?.05). The 24?h urinary protein excretion and serum cholesterol levels in both groups decreased after therapy and the serum levels of albumin in both groups increased after therapy. There were significant differences between the results for the 24?h urinary protein excretion, serum levels of albumin and cholesterol in the two groups (p?<?.05). The treatments were well tolerated in both groups.

Conclusion: LEF combined with prednisone has a certain efficacy on the RNS and displays few adverse reactions. A large-sample, randomized double-blind controlled study and long-term follow-up are needed to verify the efficacy of LEF combined with prednisone.     

Potential function of angiopoietin-like protein 3 in hyperlipidemia of nephrotic syndrome

Objective To explore whether angiopoietin-like protein 3 (Angptl3) is involved in the development of hyperlipidemia in nephrotic syndrome. Methods PCR analysis was carried out to identify the genotypes of Angptl3 Knockout mice. Sixty newborn Angptl3 knockout (KO) mice and wild type (WT) mice were randomly divided into four groups: KO-ADR, KO-Saline, WT-ADR and WT-Saline group. In each group 6 mice at different time points were separately analyzed: the pre-molding, molding 1st, 2nd, 4th, 8th week. WT-ADR and KO-ADR groups were treated with 25 mg/kg ADR once via tail vein injection at day 0; WT-saline and KO-saline groups were injected with the same volume of saline. Automatic biochemical analyzer was employed to test serum cholesterol (Cho) and triglycerides (TG) levels, ELISA method to detect the urine protein and urine creatinine, and real-time fluorescence quantitative PCR to detect the expression of Angptl3 mRNA in the renal tissue. Results (1)There were no significant differences in the weight, morphology or function of the liver and kidney between the KO and WT mice. Compared with WT mice, the levels of Cho and TG obviously decreased in the KO mice (P＜0.01). (2) In the WT-ADR group, urinary protein levels and the levels of Cho and TG increased significantly at 1st week after ADR injection (P＜0.05), while serum albumin level decreased dramatically (P＜0.05). The serum levels of Cho and TG increased gradually during the entire study period. The expressions of Angptl3 mRNA in kidney tissues were up-regulated significantly from 1st week (P＜0.05) to 8th weeks(P＜0.01). Furthermore, the expression of Angptl3 mRNA was significantly positively correlated with the Cho and TG levels (r=0.885, P＜0.01; r=0.788, P＜0.01, respectively). (3)The levels of Cho and TG in the Angptl3-/- mice were lower than those in the WT mice during the entire study period after ADR injection (P＜0.05). Conclusions Angptl3 is involved in the development of hyperlipidemia in nephrotic syndrome. Knocking-out of Angptl3 may play an anti-dyslipidemic role in nephrotic syndrome.     

The nephrotic syndrome: pathogenesis and treatment of edema formation and secondary complications

Nephrotic syndrome is an important clinical condition affecting both children and adults. Studies suggest that the pathogenesis of edema in individual patients may occur via widely variable mechanisms, i.e., intravascular volume underfilling versus overfilling. Managing edema should therefore be directed to the underlying pathophysiology. Nephrotic syndrome is also associated with clinically important complications related to urinary loss of proteins other than albumin. This educational review focuses on the pathophysiology and management of edema and secondary complications in patients with nephrotic syndrome.     

Treatment of the hyperlipidemia of the nephrotic syndrome: a controlled trial

The hyperlipidemia of the nephrotic syndrome is often associated with elevated total and low-density lipoprotein (LDL) cholesterol levels and low or normal high-density lipoprotein (HDL) cholesterol levels. This pattern of hyperlipidemia has been associated with an increased risk of accelerated atherosclerosis in other populations. Despite extensive studies of diet and drug therapy in other populations, few such therapeutic studies exist in patients with the nephrotic syndrome. To investigate the effect of diet and lipid-lowering drugs on the lipoprotein-lipid profile of patients with unremitting nephrotic syndrome and marked hyperlipidemia, we conducted a controlled trial using two such drugs: colestipol and probucol. Colestipol lowered the mean total fasting plasma cholesterol of seven patients from 397 +/- 27 to 317 +/- 37 mg/dL, a 20.2% decrease, and lowered the LDL cholesterol from 398 +/- 28 to 203 +/- 18 mg/dL, a 31.9% decrease. It did not affect the HDL cholesterol level, and thus lowered the LDL-to-HDL cholesterol ratio. Probucol lowered the mean total cholesterol from 439 +/- 72 to 339 +/- 60 mg/dL, a 22.6% decrease, and the LDL cholesterol from 282 +/- 43 to 215 +/- 26 mg/dL, a 23.8% decrease. Although the HDL cholesterol was lowered from 49 +/- 9 to 43 +/- 7 mg/dL by probucol, a 12.2% decrease, the LDL-to-HDL cholesterol ratio still declined. Both drugs were well tolerated and proved safe in this short-term trial. Antihyperlipidemic therapy may well be indicated in certain patients with unremitting nephrotic syndrome.     

吗替麦考酚酯联合低剂量激素治疗HBsAg阳性的成人微小病变性肾病综合征

目的 探讨吗替麦考酚酯（MMF）联合低剂量糖皮质激素方案治疗HBsAg阳性的成人微小病变性肾病综合征的疗效及安全性。 方法 前瞻性地选择HBsAg阳性、HBeAg 阴性及血清 HBV-DNA <1000 拷贝/ml的成人微小病变性肾病综合征患者30例,分成激素组（16例）及MMF组（14例）。激素组接受常规激素治疗方案（泼尼松片,1 mg&#8226;kg-1&#8226;d-1）;MMF组接受低剂量激素（泼尼松片,0.5 mg&#8226;kg-1&#8226;d-1）联合MMF 1.0~2.0 g/d。 结果 激素组和MMF组乙肝病毒激活发生比例分别为62.5%及35.7%,其中接受拉米呋定治疗分别为43.8%及21.4%;谷丙转氨酶升高发生比例分别为50.0%及28.6%。激素组及MMF组的完全缓解比例分别为11/14和10/12,两组复发比例分别为6/11和4/10。 结论 与常规激素治疗方案比较,MMF联合低剂量糖皮质激素方案能同样有效地治疗HBsAg阳性的成人微小病变性肾病综合征,并在减少乙肝病毒激活方面可能显示一定优势     

长春西汀联合泼尼松治疗原发性肾病综合征疗效观察

目的观察长春西汀联合泼尼松治疗原发性肾病综合征的临床疗效。方法选取原发性肾病综合征患者62例，随机分为观察组和对照组。对照组采用泼尼松及常规治疗，观察组在对照组治疗基础上给予长春西汀注射液静脉滴注，两组疗程均为3周。观察两组患者临床改善情况。结果观察组总有效率（83．9％）明显高于对照组总有效率（61．3％）（P〈0．05），两组治疗后血浆白蛋白、24h尿蛋白定量与本组治疗前比较有统计学差异（P〈0．05），观察组较对照组改善更显著（P〈0．05），观察组尿素氮、血肌酐、活化部分凝血活酶时间、纤维蛋白原、D-二聚体较治疗前明显改善（P〈0．05），与对照组相比有统计学差异（P〈0．05）。结论长春西汀联合泼尼松治疗原发性肾病综合征安全有效，能有效改善血液高凝状态。     

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.     

Effects of pravastatin on serum lipids and apolipoproteins in hyperlipidemia of the nephrotic syndrome.

The nephrotic syndrome is often accompanied by hyperlipidemia associated with an increased risk of accelerated atherosclerosis. The present study was undertaken to evaluate the effects of pravastatin, a novel competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the serum lipids and apolipoproteins in patients with this syndrome and marked hyperlipidemia. Eleven adult patients received 10 mg of pravastatin twice daily for 4 to 8 weeks. The total serum cholesterol decreased from 426 +/- 44 to 309 +/- 18 mg/dl (-27.4%, mean +/- S.E.; p less than 0.01) following administration of pravastatin. The serum triglyceride decreased from 332 +/- 122 to 229 +/- 50 mg/dl (-30.9%), although this change was not significant. Despite the fact that the HDL cholesterol level was barely changed (51 +/- 7 to 51 +/- 6 mg/dl), the LDL cholesterol fell from 313 +/- 30 to 211 +/- 16 mg/dl (-32.5%; p less than 0.005), and the LDL to HDL cholesterol ratio fell from 7.57 +/- 1.59 to 4.94 +/- 0.88 (-34.8%; p less than 0.05). These changes caused the atherogenic index to decline from 9.6 +/- 2.4 to 6.1 +/- 1.2 (-36.5%; p less than 0.05). No significant alterations could be found among apolipoproteins A-1, A-2, B, C-2, C-3, and E. During the present study period, pravastatin was well tolerated and did not affect the serum protein, albumin, serum urea nitrogen, creatinine levels, or urine protein excretion. Also, there were no serious adverse effects. Pravastatin appears to be effective for treating patients with hyperlipidemia of the nephrotic syndrome.     

来氟米特及雷公藤多甙联合泼尼松治疗难治性肾病综合征

难治性肾病综合征治疗方案的研究是肾脏疾病临床工作的重要内容。我院采用来氟米特及雷公藤多甙联合泼尼松治疗难治性肾病综合征，取得良好的效果，现报道如下。     

Complications of the nephrotic syndrome and their treatment

The nephrotic syndrome occurs in association with a diverse array of primary and secondary glomerular disorders. Despite the different etiologies, many of the clinical effects are similar. This review focuses on the pathogenesis and treatment of edema formation, hyperlipidemia, and the hypercoagulable state. Major abnormalities of the endocrine system and evidence of erythropoietin deficiency will be reviewed. Finally, non-specific treatments aimed at reducing proteinuria will also be discussed.