舒洛地特对原发性膜性肾病的疗效观察
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摘要
背景和目的
膜性肾病(membranous nephropathy, MN)是成人肾病综合征常见的病理类型,临床上原发性膜性肾病(idiopathic membranous nephropathy, IMN)约占75%-80%,其发病机制目前仍不清楚,剩余20-25%的膜性肾病继发于感染、自身免疫性疾病、肿瘤、药物等相关因素,即继发性膜性肾病(secondary membranous nephropathy)。膜性肾病的自然病程具有较大差异,部分患者可自发缓解(约占25%),部分患者则进展至终末期肾脏病(end stage renal disease, ESRD),相关报道有近40%患者在10年后发展为ESRD。目前,膜性肾病的治疗方法仍存在争议,多数学者赞同根据其预后危险程度进行个体化治疗。Cattran将膜性肾病按其进展性分为低危、中危及高危三种类型：肾功能正常、蛋白尿定量<4g/24h为低危患者；肾功能正常或基本接近正常、蛋白尿定量为4-8g/24h为中危患者；肾功能不正常或持续恶化、尿蛋白定量>8g/24h为高危患者。对于中、低危患者,应避免过于积极的使用糖皮质激素及(或)免疫抑制剂而出现严重的不良反应,可考虑仅应用非免疫抑制剂治疗,对于高危患者,则需要积极应用糖皮质激素及(或)免疫抑制剂治疗。
血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitor, ACEI)和血管紧张素Ⅱ受体拮抗剂(angiotensin receptor blocker, ARB)已成为临床上治疗MN的常规用药,它们主要通过调节肾小球血流动力学、调节基底膜(Glomerular basement membrane, GBM)的滤过孔径影响GBM的滤过屏障,并抑制炎性细胞因子的生成与释放等机制减少尿蛋白。ACEI/ARB类药物达到减少尿蛋白的疗效呈剂量依赖性,但膜性肾病患者中约70%血压正常,部分患者难以耐受ACEI/ARB类药物引起的干咳、体位性低血压等症状,副作用不容忽视。
舒洛地特是一种天然的糖胺聚糖(glycosaminoglycans, GAGs),含有低分子肝素和硫酸皮肤素两种主要成分。近年来国内外的动物及临床药物实验均表明,舒洛地特对减少糖尿病肾病(Diabetic nephropathy, DN)尿蛋白具有显著效果,现阶段研究表明舒洛地特对足细胞及GBM的保护作用为减少DN蛋白尿的主要机制。原发性膜性肾病是足细胞病之一,在MN的病理发病过程中以足细胞的损伤为主。由于舒洛地特具有良好的抗凝、调脂及血管内皮保护等作用,且为口服制剂服用方便,在心脑血管疾病、糖尿病肾病及其他糖尿病并发症、代谢综合征肾损害、高血压肾损害等领域的应用越来越广泛,但是有关舒洛地特在原发性膜性肾病中的临床研究鲜有报道。本研究应用舒洛地特及联合替米沙坦治疗IMN中、低危患者,观察其临床疗效和不良反应,探讨舒洛地特对IMN治疗的有效性。
方法
将经过肾脏活检证实,并排除糖尿病肾病、系统性红斑狼疮-狼疮肾炎、病毒性肝炎相关性肾病等继发性膜性肾病的51例IMN中、低危患者随机分为3个治疗组：舒洛地特组,替米沙坦组和联合治疗组,所有病人均随访6个月,随访过程中定期监测患者的24小时尿蛋白定量、血浆白蛋白、肝功能、肾功能、血脂、血压及不良反应。
结果
1.治疗后三组病人尿蛋白水平及血浆白蛋白水平较治疗前均明显改善,其中舒洛地特组24小时尿蛋白定量水平较治疗前下降44.36%,替米沙坦组下降48.74%,联合治疗组下降72.24%。舒洛地特组尿蛋白量下降水平与替米沙坦组比较差异无统计学意义(P>0.05),两组与联合治疗组比较差异均有统计学意义(P<0.05)。
2.三组患者肝肾功能、血脂、血压及在治疗前后差异无统计学意义(P>0.05)。
3.替米沙坦组出现肝功能轻度损害一例,替米沙坦组和联合治疗组出现体位性低血压各一例。
结论
1.舒洛地特能有效降低IMN中、低危患者尿蛋白水平,效果与替米沙坦相当。
2.舒洛地特联合替米沙坦能有效降低IMN中、低危患者的尿蛋白水平,效果优于单一用药。
3.舒洛地特无明显肝肾功损害、出血、低血压等副作用,临床应用安全。
Backgroud and Objective
Membranous nephropathy(MN) is one common pathological type of adult nephrotic syndrome(NS). Of the total MN, idiopathic membranous nephropathy(IMN) accounts for about75%～80%, and by now the pathogenesis of IMN is still unknown; The remaining20%～25%of MN is the secondary membranous nephropathy, which often occurs secondary to some other diseases, such as infection, autoimmune diseases, neoplasm, and some medication. The natural course of MN has large difference, some of MN patients can relieve itself(about25-30%), however, some of them will eventually progress to end-stage kidney(ESRD). There is one report demonstrating that about40%of MN will develop into ESRD finally. Presently the therapy for MN is controversial, most scholars agree that MN patients should be given individualized treatments according to their different risk degree of prognosis and should avoid actively using of glucocorticoid and (or) immune inhibitors for patients with low risk, since it could generate serious adverse reactions. MN was divided into three types by Cattran on the basis of its progressivity:the low-risk MN patients have normal renal function and the quantitative proteinuria is less than4g/24h; the intermediate risk MN patients have normal or near normal renal function and the quantitative proteinuria is4-8g/24h; the high risk MN patients have abnormal or deteriorated renal function and the urine protein quantitative is greater than8g/24h. For medium and low risk patients, treatments except immunosuppressant can be only considered, whereas for high-risk patients, they should be given active application of immunosuppressive therapy.
The angiotensin converting enzyme inhibitor(ACEI) and angiotensin receptor blocker(ARB) have been the routine drugs for low risk and intermediate risk MN patients. ACEI/ARB show dose-dependent effect for reducing urinary protein. However, the side effect should be noted since70%of MN patients have normal blood pressure, and some of them can not tolerate symptoms of low blood pressure caused by ACEI/ARB drugs.
Sulodexide is a kind of natural glycosaminoglycans(GAGs), which contains low molecular weight heparin and dermatan sulfate, and the two main ingredients have different working mechanisms and provide synergistic effects for MN therapy. For the past few years, Sulodexide has showed significant effect for reducing urinary protein in the secondary membranous nephropathy caused by diabetic nephropathy(DN), meanwhile present researches indicate that the primary mechanism of Sulodexide to reduce proteinuria of DN due to the protection for sertoli cell and glomerular basement membrane(GBM). IMN is one of Sertoli cell disease, and hormone and immune inhibitor have poor curative effects for some patients. Meanwhile, most of the researches aim at the studies about curative effect of Sulodexide for diabetic nephropathy,metabolic syndrome kidney damage and Cardiovascular and cerebrovascular diseases currently, nevertheless there were few reports about Sulodexide for IMN. The present study is to analyse the effectiveness of Sulodexide for IMN patients with low and intermediate risk by means of observing clinical efficacy and adverse reactions when using Sulodexide alone and combined using telmisartan treatment.
Methods
Total one fifty patients with low-intermediate risk IMN, which have been confirmed by the kidney biopsy and excluded the secondary membranous nephropathy generated from DN, systemic lupus erythematosus-lupus nephritis, viral hepatit and so on, were randomly devided into three treatment groups:Sulodexide therapy group, Telmisartan therapy group and combination therapy group. All patients were followed up for6months, when24-hour urinary protein quantity, plasma albumin, liver function, renal function, blood lipid, blood pressure and untoward effect were monitored periodically.
Results
1.Urine protein and plasma albumin levels in all three groups of patients were obviously improved after treatment. Compared with before, the24hours urine protein quantitative level decreased by44.36%in Sulodexide therapy group, which had no statistically significant difference compared to48.74%in Telmisartan therapy group. Result were significantly decreased by72.24%in combination therapy group compared with the above two single drug treatment groups;
2. Liver function, renal function, blood lipid and blood pressure were no significant change in all therapy groups(P>0.05);
3. One patient showed mild liver damage after using Telmisartan, postural hypotension occurred in Telmisartan therapy group and combination therapy group and each one in each group.
Conclusions
Sulodexide can effectively reduce the urinary protein of low-intermediate risk IMN patients, which has the same effect as Telmisartan, and the medicinal effect of combination with Telmisartan was superior to that of single Sulodexide using. It is safe to apply Sulodexide as there are no obvious liver and kidney function damage, hemorrhage, hypotension and other side effects.
膜性肾病(membranous nephropathy, MN)是成人肾病综合征常见的病理类型,临床上原发性膜性肾病(idiopathic membranous nephropathy, IMN)约占75%-80%,其发病机制目前仍不清楚,剩余20-25%的膜性肾病继发于感染、自身免疫性疾病、肿瘤、药物等相关因素,即继发性膜性肾病(secondary membranous nephropathy)。膜性肾病的自然病程具有较大差异,部分患者可自发缓解(约占25%),部分患者则进展至终末期肾脏病(end stage renal disease, ESRD),相关报道有近40%患者在10年后发展为ESRD。目前,膜性肾病的治疗方法仍存在争议,多数学者赞同根据其预后危险程度进行个体化治疗。Cattran将膜性肾病按其进展性分为低危、中危及高危三种类型：肾功能正常、蛋白尿定量<4g/24h为低危患者；肾功能正常或基本接近正常、蛋白尿定量为4-8g/24h为中危患者；肾功能不正常或持续恶化、尿蛋白定量>8g/24h为高危患者。对于中、低危患者,应避免过于积极的使用糖皮质激素及(或)免疫抑制剂而出现严重的不良反应,可考虑仅应用非免疫抑制剂治疗,对于高危患者,则需要积极应用糖皮质激素及(或)免疫抑制剂治疗。
血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitor, ACEI)和血管紧张素Ⅱ受体拮抗剂(angiotensin receptor blocker, ARB)已成为临床上治疗MN的常规用药,它们主要通过调节肾小球血流动力学、调节基底膜(Glomerular basement membrane, GBM)的滤过孔径影响GBM的滤过屏障,并抑制炎性细胞因子的生成与释放等机制减少尿蛋白。ACEI/ARB类药物达到减少尿蛋白的疗效呈剂量依赖性,但膜性肾病患者中约70%血压正常,部分患者难以耐受ACEI/ARB类药物引起的干咳、体位性低血压等症状,副作用不容忽视。
舒洛地特是一种天然的糖胺聚糖(glycosaminoglycans, GAGs),含有低分子肝素和硫酸皮肤素两种主要成分。近年来国内外的动物及临床药物实验均表明,舒洛地特对减少糖尿病肾病(Diabetic nephropathy, DN)尿蛋白具有显著效果,现阶段研究表明舒洛地特对足细胞及GBM的保护作用为减少DN蛋白尿的主要机制。原发性膜性肾病是足细胞病之一,在MN的病理发病过程中以足细胞的损伤为主。由于舒洛地特具有良好的抗凝、调脂及血管内皮保护等作用,且为口服制剂服用方便,在心脑血管疾病、糖尿病肾病及其他糖尿病并发症、代谢综合征肾损害、高血压肾损害等领域的应用越来越广泛,但是有关舒洛地特在原发性膜性肾病中的临床研究鲜有报道。本研究应用舒洛地特及联合替米沙坦治疗IMN中、低危患者,观察其临床疗效和不良反应,探讨舒洛地特对IMN治疗的有效性。
方法
将经过肾脏活检证实,并排除糖尿病肾病、系统性红斑狼疮-狼疮肾炎、病毒性肝炎相关性肾病等继发性膜性肾病的51例IMN中、低危患者随机分为3个治疗组：舒洛地特组,替米沙坦组和联合治疗组,所有病人均随访6个月,随访过程中定期监测患者的24小时尿蛋白定量、血浆白蛋白、肝功能、肾功能、血脂、血压及不良反应。
结果
1.治疗后三组病人尿蛋白水平及血浆白蛋白水平较治疗前均明显改善,其中舒洛地特组24小时尿蛋白定量水平较治疗前下降44.36%,替米沙坦组下降48.74%,联合治疗组下降72.24%。舒洛地特组尿蛋白量下降水平与替米沙坦组比较差异无统计学意义(P>0.05),两组与联合治疗组比较差异均有统计学意义(P<0.05)。
2.三组患者肝肾功能、血脂、血压及在治疗前后差异无统计学意义(P>0.05)。
3.替米沙坦组出现肝功能轻度损害一例,替米沙坦组和联合治疗组出现体位性低血压各一例。
结论
1.舒洛地特能有效降低IMN中、低危患者尿蛋白水平,效果与替米沙坦相当。
2.舒洛地特联合替米沙坦能有效降低IMN中、低危患者的尿蛋白水平,效果优于单一用药。
3.舒洛地特无明显肝肾功损害、出血、低血压等副作用,临床应用安全。
Backgroud and Objective
Membranous nephropathy(MN) is one common pathological type of adult nephrotic syndrome(NS). Of the total MN, idiopathic membranous nephropathy(IMN) accounts for about75%～80%, and by now the pathogenesis of IMN is still unknown; The remaining20%～25%of MN is the secondary membranous nephropathy, which often occurs secondary to some other diseases, such as infection, autoimmune diseases, neoplasm, and some medication. The natural course of MN has large difference, some of MN patients can relieve itself(about25-30%), however, some of them will eventually progress to end-stage kidney(ESRD). There is one report demonstrating that about40%of MN will develop into ESRD finally. Presently the therapy for MN is controversial, most scholars agree that MN patients should be given individualized treatments according to their different risk degree of prognosis and should avoid actively using of glucocorticoid and (or) immune inhibitors for patients with low risk, since it could generate serious adverse reactions. MN was divided into three types by Cattran on the basis of its progressivity:the low-risk MN patients have normal renal function and the quantitative proteinuria is less than4g/24h; the intermediate risk MN patients have normal or near normal renal function and the quantitative proteinuria is4-8g/24h; the high risk MN patients have abnormal or deteriorated renal function and the urine protein quantitative is greater than8g/24h. For medium and low risk patients, treatments except immunosuppressant can be only considered, whereas for high-risk patients, they should be given active application of immunosuppressive therapy.
The angiotensin converting enzyme inhibitor(ACEI) and angiotensin receptor blocker(ARB) have been the routine drugs for low risk and intermediate risk MN patients. ACEI/ARB show dose-dependent effect for reducing urinary protein. However, the side effect should be noted since70%of MN patients have normal blood pressure, and some of them can not tolerate symptoms of low blood pressure caused by ACEI/ARB drugs.
Sulodexide is a kind of natural glycosaminoglycans(GAGs), which contains low molecular weight heparin and dermatan sulfate, and the two main ingredients have different working mechanisms and provide synergistic effects for MN therapy. For the past few years, Sulodexide has showed significant effect for reducing urinary protein in the secondary membranous nephropathy caused by diabetic nephropathy(DN), meanwhile present researches indicate that the primary mechanism of Sulodexide to reduce proteinuria of DN due to the protection for sertoli cell and glomerular basement membrane(GBM). IMN is one of Sertoli cell disease, and hormone and immune inhibitor have poor curative effects for some patients. Meanwhile, most of the researches aim at the studies about curative effect of Sulodexide for diabetic nephropathy,metabolic syndrome kidney damage and Cardiovascular and cerebrovascular diseases currently, nevertheless there were few reports about Sulodexide for IMN. The present study is to analyse the effectiveness of Sulodexide for IMN patients with low and intermediate risk by means of observing clinical efficacy and adverse reactions when using Sulodexide alone and combined using telmisartan treatment.
Methods
Total one fifty patients with low-intermediate risk IMN, which have been confirmed by the kidney biopsy and excluded the secondary membranous nephropathy generated from DN, systemic lupus erythematosus-lupus nephritis, viral hepatit and so on, were randomly devided into three treatment groups:Sulodexide therapy group, Telmisartan therapy group and combination therapy group. All patients were followed up for6months, when24-hour urinary protein quantity, plasma albumin, liver function, renal function, blood lipid, blood pressure and untoward effect were monitored periodically.
Results
1.Urine protein and plasma albumin levels in all three groups of patients were obviously improved after treatment. Compared with before, the24hours urine protein quantitative level decreased by44.36%in Sulodexide therapy group, which had no statistically significant difference compared to48.74%in Telmisartan therapy group. Result were significantly decreased by72.24%in combination therapy group compared with the above two single drug treatment groups;
2. Liver function, renal function, blood lipid and blood pressure were no significant change in all therapy groups(P>0.05);
3. One patient showed mild liver damage after using Telmisartan, postural hypotension occurred in Telmisartan therapy group and combination therapy group and each one in each group.
Conclusions
Sulodexide can effectively reduce the urinary protein of low-intermediate risk IMN patients, which has the same effect as Telmisartan, and the medicinal effect of combination with Telmisartan was superior to that of single Sulodexide using. It is safe to apply Sulodexide as there are no obvious liver and kidney function damage, hemorrhage, hypotension and other side effects.
引文
[1]Piero Ruggenenti, MD, Paolo Cravedi MD, Giuseppe Remuzzi. Latest treatmentstrategies for membranous nephropathy[J]. Expert Opin Pharmacother.2007; 8(18):3159-3171.
[2]Cattarn DC. Idiopathic membranous glomerulonephritis[J]. Kidney Int,2001,59:1983-1994.
[3]Nakao N,Yoshimura,Morita H,et al.Combination treatment of angiotenain-Ⅱ receptor blocker and angiotenain convert ingenzyme inhibitor in non-diabetic renal disease (COOPERATE):A randomized controlled trial[J].Lancet,2003; 361(9352):117-124.
[4]Adiguzel C, Iqbal O, Hoppensteadt D et al. Comparative Anticoagulant and Platelet M odulatory.Effects of Enoxaparin and Sulodexide[J]. Clin ApplThromb H emost,2009; 15(5):501-511.
[5]Barbanti M, Guizzardi S, Calanni F, et al. Antithrombotic and thrombolytic activity of sulodexide in rats [J]. Int J Clin Lab Res,199; 22(3):179-184.
[6]Lauver DA, Booth EA, White AJ, et al. Sulodexide attenuates myocar dia 1 ischemia reperfusion injury and the depositio n of C-reactive pro tein in areas of infarction without affecting hemostasis[J]. J Pharmacol Exp Ther,2005,312(2):794-800.
[7]王亚敏.舒洛地特研究进展及临床应用[J].中国临床药理学与治疗学,2010,15(1)：109-115.
[8]Radhakrishnamurthy B, Sharma C, Bhandaru RR, et al. Studies of chemical and biologic properties of a fraction of sulodexide, a heparin-like glycosaminoglycan[J]. Atherosclerosis, 1986; 60(2):141-149.
[9]Heerspink HL, Greene T, Lew is JB, et al. Effects of sulodex ide in patients w ith type 2 diabetes and per sistent albuminuria [J]. Nephr ol Dial T ransplant,2008; 23(6):1946-1954.
[10]Maruyama M, Sugiyama H, Sada K, et al. Desmin as a marker of proteinuria in early stages of membranous nephropathy in elderly patients[J]. Clin Nephrol,2007; 68(2):73-80.
[11]Ceol M, Gambaro G, Sauer U, et al. Glycosaminoglycan therapy prevents TGF-betal overexpression and pathologic changes in renal tissue of long term diabetic rats [J].Am Soc Nephrol,2000,11:2324-2336.
[12]Ohashi T, Uchida K, Yumura W, et al. Membranous glomerulonephritis(membranous-nephropathy):pathogenesis, patho-physiology, and therapy[J]. Nippon Rinsho,2006; 64(12):417-421.
[13]章洁,王丹,马恒颢,等.肾局部内皮素与蛋白尿关系的实验骈究[J].中华肾脏病杂志,2000；16(4)：261—262.
[14]纪泽泉,黄翠雯,梁成结,等.阻断肾素-血管紧张素对肾病大鼠肾小球硬化ET-1及NO的作用[J].中国医师杂志,2004；6(9)：1167-1169.
[15]Nakamura T, Ebihara I, Fukui M, et al. Effect of a specific endothelinle.receptorA antagonist on mRNA levels for extracellular matrix components.An growth factors in diabetic glomeruli[J]. Diabetes,1995; 44(8):895-899.
[16]陈楠.膜性肾病的治疗[J].肾脏病与透析肾移植杂志,2002,11(3)：251-252.
[17]Haraldsson B, Nystrom J, Deen WM. Properties of the glomeruar barrier and mechanisms of proteinuria[J]. Physiol Rev,2008; 88 (2):451-487.
[18]Erdely A, Freshour G, M addox DA, et al. Renal disease in rats with type 2 diabetes is also ciated with decreased renal nitric oxide production[J]. Diabetologia,2004; 47(10):1672-1676.
[19]Piqueras L, Kubes P, Alvare zA, et al. Angiotensin Ⅱ induces leukocyte-endothelial cell interactions in vivo via AT(1) and AT(2) receptor-mediated P-selectin upregulation[J]. Circulation,2000; 102(17):2118-2123.
[20]Deckert T. Nephropathy and coronary death:the fatal twins in diabetes mellitus[J].Nephrol Dial Transplant,1994,9:1069.
[21]梁伟,余碧影,丁国华,等.舒洛地特对糖尿病高血压大鼠足细胞podocalyxin表达的影响[J].中华肾脏病杂志,2009；25(7)：497-502.
[22]舒同,曾龙驿,王曼曼,等.舒洛地特对大鼠糖尿病肾脏的保护作用及其机制[J].中国医院药学杂志,2009；29(1)：19-23.
[23]Karon J, Polubinska A, Antoniewicz AA, et al. Anti-inflammatory effect of sulodexide during acute peritonitis in rats[J]. Blood Purif,2007; 25(5-6):510-514.
[24]Fem iano F, Gom bos F, Scully C. Recurrent aphthous stomatitis unresponsive to topical corticosteroids:a study of the comparative therapeutic effects of systemic prednisone and systemic sulodexide[J]. In t J Derm tol,2003; 42(5):394-397.
[25]Jurgen F, Eudora E, Bessie Y, et al. Heparin suppresses mesangial cell proliferation and matrix expansion in experimental mesangioproliferative glomerulonephritis[J]. Kidney Int, 1993; 43(2):369-380.
[26]林可意,曾龙驿,舒同,等.舒洛地特对糖尿病大鼠尿白蛋白排泄率及肾脏转化生长因子-1表达的影响[J].中华糖尿病杂志,2009；,1(3)：196-200.
[27]徐海平,郑红光.舒洛地特对糖尿病大鼠的肾脏保护作用[J].沈阳部队医药,2009；22(3)：172-176.
[28]Mandal AK, Lyden TW, Saklayen MG. Heparin lowers blood pressure:biological and clinical perspectives[J]. Kidney Int,1995; 47(4):1017-1022.
[29]Weiss R, NiecestroR, Raz I. The role of sulodexide in the treatment of diabetic nephropathy[J]. Drugs,2007; 67(18):2681-2696.
[30]李大勇,曹海霞,范亚平,等.膜性肾病肾活检组织中TRPC6和lpodocalyxin表达改变及其意义[J].临床与实验病理学杂志,2012；28(5)：486-489.
[31]贾冶,王晶,顾华,等.FK506治疗大鼠早期膜性肾病的实验研究[J].中国老年学杂志,2009；29(16)：2061-2064.
[32]Mezzano S, Aros C, Droguett A, et al. NF-kappa B activation and overexpression of regulated genes in human diabetic nephropathy [J]. Nephrol Dial Transplant,2004; 19(10): 2505-2512.
[33]Van den Hoven MJ, Rops AL, Bakker MA, et al. Increased expression of heparanase in oven diabetic nephmpathy[J]. Kidney Int,2006; 70(12):1287-1296.
[34]姚素花,王彦,陈凤慧,等.乙酰肝素酶、血管内皮生长因子和核因子-κB在原发性膜性肾病患者肾小球内的表达变化及意义[J].中国美容医学,2012；21(z1)：37-39.
[35]舒同.舒洛地特对糖尿病大鼠肾脏NF-κB、ICAM-1表达的影响及肾保护作用[D].广州,中山大学硕士学位论文,2007.
[36]杜江涛,王建生,赵瑛瑛,等.舒洛地特对糖尿病肾病大鼠肾脏乙酰肝素酶及碱性成纤维细胞生长因子表达影响[J].中华实用诊断与治疗杂志,2011；25(3)：253-254.
[37]廖丹,白云凯,肖欢,等.乙酰肝素酶在慢性肾脏疾病患者肾组织中的表达及其意义[J].国际泌尿系统杂志,2012；32(6)：768-770.
[38]Nosadini R, Velussi M, Broeeo E, et al. Altered transcapillary escape of albumin and microalbuminuria reflects two different pathogenefic mechanisms[J]. Diabetes,2005, 54(1):228-233.
[1]Laluck BJ Jr., Catttran DC. Prognosis after a complete remission in adult patients with idiopathic membranous nephropathy[J]. Am J Kid Dis,1993;33(6):1026-1032
[2]Chen A, Frank R, Vento S, et al. Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome[J]. BMC Nephrol 2007;8:11.
[3]Ponticelli C. Membranous nephropathy[J]. J Nephrol 2007; 20(3):268-87.
[4]Kerjaschki D. Molecular pathogenesis of membranous nephropathy[J]. Kidney Int, 1992; 41 (4):1090-1105.
[5]达展云,崔世维,钱桐荪.Heymann肾炎抗原及免疫复合物的研究进展[J].国外医学·泌尿系统分册.2000；20(增刊)：23—24.
[6]Beck LH Jr, Bonegio RG, I,ambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy[J]. N Engl J Med,2009; 361:11-21.
[7]曲贞,刘刚.特发性膜性肾病发病机制的研究进展[J].临床肾脏病杂志,2012；12(1)：7-8.
[8]Beck LH Jr, Fervenza FC, Beck DM, et al. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy [J]. J Am Soc Nephrol.2011; 22(8):1543-50.
[9]Qin w, Beck LH Jr, Zeng C, et al. Anti -phospholipase A2 receptor antibody in nlenlbranous nephropathy[J]. J Am Soc Nephrol,2011; 22:1137-1143.
[10]周广宇,金玲,于晶,等.成人膜性肾病患者血清抗PLA2R抗体与病情的相关性[J].中华肾脏病杂志,2012；28(2)：111-114.
[11]Stanescu HC, Arcos-Burgos M, Medlar A, et al. Risk HLA-DQAI and PLA(2)R1 alleles in idiopathic membranous nephropathy [J]. N Engl J Med,2011; 364:616-626
[12]Lin YH, Chen CH, Chen SY, et al. Association of phospholipaseA2 receptor 1 polymorphisms with idiopathic membranous nephropathy in Chinese patients in Taiwan[J]. J Biomed Sci,2010;17:81.
[13]Prunotto M Autoimmunity in membranous nephropathy targets aldose reductase and S0D2[J]. J Am Soc Nephrol,2010; 3:507-519.
[14]Stanescu HC, Arcos-Burgos M, Medlar A, et al. Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy [J]. N Engl J Med.2011; 364(7):616-26.
[15]Debiec H, Lefeu F, Kemper MJ,et al. Early-childhood membranous nephropathy due to cationic bovine serum albumin[J]. N Engl J Med,2011; 364(22):2101-10.
[16]Zhang H. Ding J, Fan Q, et al. TRPC6 Up-docyte apoptosis might result from ERK activation and NF-κB translocation[J]. Exp Biol Med,2009; 234(9):1029-1036.
[17]Ohashi T, Uchida K, Yumura W, et al. Membranous glomerulonephritis (membranous nephropathy):pathogenesis, pathophysiology,and therapy [J]. Nippon Rinsho,2006; 64(12): 417-421.
[18]Kuroki A, lyoda M, Shibata T, Sugisaki T. Th2 cytokines increase and stimulate B cells to produce IgG4 in idiopathic membranous nephropathy[J]. Kidney Int,2005;68(1): 302-310.
[19]Kawasaki Y, Suzuki J, Sakai N,et al. Evaluation of T helper-1/-2 balance on the basis of IgG subclasses and serum cytokines in children with glomerulonephritis [J]. Am J Kidney Dis,2004; 44(1):42-9.
[20]Cunningham PN, Quigg RJ. Contrasting roles of complement activation and its regulation in membranous nephropathy[J]. J Am Soc Nephrol.2005; 16(5):1214-22.
[21]Segawa Y, Hisano S, Matsushita M, et al. IgG subclasses and complement pathway in segmental and global membranous nephropathy[J]. Pediatr Nephrol,2010; 25(6): 1091-1099.
[22]Hyun SL. Pathogenic role of TGP-13 in the progression of podocyte diseases[J], Histol Histopatho,2011; 26(1):107-116.
[23]梅长林,刘亚伟.特发性膜性肾病的治疗评价[J].继续医学教育,2006；20(5)：8-11.
[24]Jha V, Ganguli A, Saha TK, et al. A randomized, cortrolled trial of steroids and cyclopho-sphamide in adlts with nephrotic synrome caused by id iopathic embranos nephropathy[J]. J Am SocNephrol,2007; 18(6):1899-1904.
[25]Ponticelli C, Zucchelli P, Passerini P, et al. A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy [J]. Kidney Int,1995; 48 (5):1600-1604.
[26]丛敏,江蓓,胡昭,等.来氟米特治疗原发性肾病综合征的多中心临床观察[J].山东大学学报(医学版),2007；45(3)：295-298.
[27]Wozel G, Pfeiffer C. Leflunomide-a new drug for pharmacological immunomodulation[J]. Hautarzt.,2002; 53(5):309-15.
[28]朱开颜,毕春艳.来氟米特治疗膜性肾病的疗效观察[J].中国实用医药,2009；4(32)：99-100.
[29]熊晓玲.特发性膜性肾病的治疗进展[J].国外医学泌尿系统分册,2004；24(1)：131-133.
[30]Meyrier A. Treatment of glomerular disease with cyclosporine A[J]. Nephrol Dialy Transplant,1989; 4:923
[31]Wetzels JF. Tacrolimus in membranous nephropathy[J]. Kidney Int,2008,73(2):238.
[32]孙广东,许钟镐,罗萍,苗里宁.他克莫司治疗特发性膜性肾病的临床疗效观察[J].中国老年学杂志,2008；28(5)：469-471.
[33]Xie G, Xu J, Ye C, et al. Immunosuppressive Treatment for Nephrotic Idiopath Membranous Nephropathy:A Meta-Analysis Based on Chinese Adults[J]. PLoS One. 2012;7(9):e44330.
[34]刘少军,顾勇,杨海春,等.霉酚酸酯对肾大部切除大鼠肾脏的保护作用[J].中华肾脏病杂志,2002；18：199.
[35]Kobayashi M, Kojima C, Sugiura H, et al. Case of MMF monotherapy for membranous nephropathy[J]. Nihon Jinzo Gakkai Shi,2010; 52(5):572-7.
[36]张翥,张淅涛,马继伟,刘浩飞.吗替麦考酚酯联合小剂量激素治疗膜性肾病的疗效观察[J].中国中西医结合肾病杂志,2012；12(1)：59-60.
[37]Chen Y, Schieppati A, Cai G, et al. Immunosuppression for Membranous Nephropathy:A Systematic Review and Meta-Analysis of 36 Clinical Trials[J]. Clin J Am Soc Nephrol. 2013[Epub ahead of prin].
[38]Fervenza FC, Cosio FG, Erickson SB, et al. Rituximab treatment of idiopathic membranous nephropathy[J]. Kidney Int,2008; 73(1):117-125.
[39]Fervenza FC, Abraham RS, Erickson SB, et al. Rituximab therapy in idiopathic membranousn ephropathy:a 2-year study[J]. Clin J Am Soc Nephrol,2010; 5(12): 2188-2198.
[40]Ruggenenti P, Cravedi P, Chianca A, et al. Rituximab in idiopathic membranous nephropathy [J]. J Am Soc Nephrol.2012; 23(8):1416-25.
[41]章洁,王丹,马恒颢,等.肾局部内皮素与蛋白尿关系的实验骈究[J].中华肾脏病杂志,2000；16(4)：261—262.
[42]Nakamura T, Ebihara I, Fukui M, et al. Effect of a specific endothelinle。receptorA antagonist on mRNA levels for extracellular matrix components an growth factors in diabetic glomeruli[J]. Diabetes,1995,44(8):895-899.
[43]刘志红,李世军,吴燕,等.雷公藤多苷联合小剂量激素治疗特发性膜性肾病前瞻性对照研究[J].肾脏病与透析肾移植杂志,2009；18(4)：303—309.
[44]何志军,马路,潘涛,武强.联合雷公藤多甙片、激素及中草药治疗老年膜性肾病的临床观察[J].临床肾脏病杂志,2012；12(7)：325-326.
[45]秦卫松,刘志红,曾彩虹,等.霄公藤甲素对Heymann肾炎模型足细胞病变的影响[J].肾脏病与透析肾移植杂志,2007；16(2)：101—109.
[46]陈朝红,刘志红,洪亦眉,等.雷公藤甲素干预C5b-9诱导足细胞损伤的体外研究[J].肾脏病与透析肾移植杂志,2009；18(4)：310-317.
[47]Ruggenenti P, Cravedi P, Remuzzi G. Latest treatmentstrategies for membranous nephropathy[J]. Expert Opin Pharmacother,2007; 8(18):3159-3171.
[2]Cattarn DC. Idiopathic membranous glomerulonephritis[J]. Kidney Int,2001,59:1983-1994.
[3]Nakao N,Yoshimura,Morita H,et al.Combination treatment of angiotenain-Ⅱ receptor blocker and angiotenain convert ingenzyme inhibitor in non-diabetic renal disease (COOPERATE):A randomized controlled trial[J].Lancet,2003; 361(9352):117-124.
[4]Adiguzel C, Iqbal O, Hoppensteadt D et al. Comparative Anticoagulant and Platelet M odulatory.Effects of Enoxaparin and Sulodexide[J]. Clin ApplThromb H emost,2009; 15(5):501-511.
[5]Barbanti M, Guizzardi S, Calanni F, et al. Antithrombotic and thrombolytic activity of sulodexide in rats [J]. Int J Clin Lab Res,199; 22(3):179-184.
[6]Lauver DA, Booth EA, White AJ, et al. Sulodexide attenuates myocar dia 1 ischemia reperfusion injury and the depositio n of C-reactive pro tein in areas of infarction without affecting hemostasis[J]. J Pharmacol Exp Ther,2005,312(2):794-800.
[7]王亚敏.舒洛地特研究进展及临床应用[J].中国临床药理学与治疗学,2010,15(1)：109-115.
[8]Radhakrishnamurthy B, Sharma C, Bhandaru RR, et al. Studies of chemical and biologic properties of a fraction of sulodexide, a heparin-like glycosaminoglycan[J]. Atherosclerosis, 1986; 60(2):141-149.
[9]Heerspink HL, Greene T, Lew is JB, et al. Effects of sulodex ide in patients w ith type 2 diabetes and per sistent albuminuria [J]. Nephr ol Dial T ransplant,2008; 23(6):1946-1954.
[10]Maruyama M, Sugiyama H, Sada K, et al. Desmin as a marker of proteinuria in early stages of membranous nephropathy in elderly patients[J]. Clin Nephrol,2007; 68(2):73-80.
[11]Ceol M, Gambaro G, Sauer U, et al. Glycosaminoglycan therapy prevents TGF-betal overexpression and pathologic changes in renal tissue of long term diabetic rats [J].Am Soc Nephrol,2000,11:2324-2336.
[12]Ohashi T, Uchida K, Yumura W, et al. Membranous glomerulonephritis(membranous-nephropathy):pathogenesis, patho-physiology, and therapy[J]. Nippon Rinsho,2006; 64(12):417-421.
[13]章洁,王丹,马恒颢,等.肾局部内皮素与蛋白尿关系的实验骈究[J].中华肾脏病杂志,2000；16(4)：261—262.
[14]纪泽泉,黄翠雯,梁成结,等.阻断肾素-血管紧张素对肾病大鼠肾小球硬化ET-1及NO的作用[J].中国医师杂志,2004；6(9)：1167-1169.
[15]Nakamura T, Ebihara I, Fukui M, et al. Effect of a specific endothelinle.receptorA antagonist on mRNA levels for extracellular matrix components.An growth factors in diabetic glomeruli[J]. Diabetes,1995; 44(8):895-899.
[16]陈楠.膜性肾病的治疗[J].肾脏病与透析肾移植杂志,2002,11(3)：251-252.
[17]Haraldsson B, Nystrom J, Deen WM. Properties of the glomeruar barrier and mechanisms of proteinuria[J]. Physiol Rev,2008; 88 (2):451-487.
[18]Erdely A, Freshour G, M addox DA, et al. Renal disease in rats with type 2 diabetes is also ciated with decreased renal nitric oxide production[J]. Diabetologia,2004; 47(10):1672-1676.
[19]Piqueras L, Kubes P, Alvare zA, et al. Angiotensin Ⅱ induces leukocyte-endothelial cell interactions in vivo via AT(1) and AT(2) receptor-mediated P-selectin upregulation[J]. Circulation,2000; 102(17):2118-2123.
[20]Deckert T. Nephropathy and coronary death:the fatal twins in diabetes mellitus[J].Nephrol Dial Transplant,1994,9:1069.
[21]梁伟,余碧影,丁国华,等.舒洛地特对糖尿病高血压大鼠足细胞podocalyxin表达的影响[J].中华肾脏病杂志,2009；25(7)：497-502.
[22]舒同,曾龙驿,王曼曼,等.舒洛地特对大鼠糖尿病肾脏的保护作用及其机制[J].中国医院药学杂志,2009；29(1)：19-23.
[23]Karon J, Polubinska A, Antoniewicz AA, et al. Anti-inflammatory effect of sulodexide during acute peritonitis in rats[J]. Blood Purif,2007; 25(5-6):510-514.
[24]Fem iano F, Gom bos F, Scully C. Recurrent aphthous stomatitis unresponsive to topical corticosteroids:a study of the comparative therapeutic effects of systemic prednisone and systemic sulodexide[J]. In t J Derm tol,2003; 42(5):394-397.
[25]Jurgen F, Eudora E, Bessie Y, et al. Heparin suppresses mesangial cell proliferation and matrix expansion in experimental mesangioproliferative glomerulonephritis[J]. Kidney Int, 1993; 43(2):369-380.
[26]林可意,曾龙驿,舒同,等.舒洛地特对糖尿病大鼠尿白蛋白排泄率及肾脏转化生长因子-1表达的影响[J].中华糖尿病杂志,2009；,1(3)：196-200.
[27]徐海平,郑红光.舒洛地特对糖尿病大鼠的肾脏保护作用[J].沈阳部队医药,2009；22(3)：172-176.
[28]Mandal AK, Lyden TW, Saklayen MG. Heparin lowers blood pressure:biological and clinical perspectives[J]. Kidney Int,1995; 47(4):1017-1022.
[29]Weiss R, NiecestroR, Raz I. The role of sulodexide in the treatment of diabetic nephropathy[J]. Drugs,2007; 67(18):2681-2696.
[30]李大勇,曹海霞,范亚平,等.膜性肾病肾活检组织中TRPC6和lpodocalyxin表达改变及其意义[J].临床与实验病理学杂志,2012；28(5)：486-489.
[31]贾冶,王晶,顾华,等.FK506治疗大鼠早期膜性肾病的实验研究[J].中国老年学杂志,2009；29(16)：2061-2064.
[32]Mezzano S, Aros C, Droguett A, et al. NF-kappa B activation and overexpression of regulated genes in human diabetic nephropathy [J]. Nephrol Dial Transplant,2004; 19(10): 2505-2512.
[33]Van den Hoven MJ, Rops AL, Bakker MA, et al. Increased expression of heparanase in oven diabetic nephmpathy[J]. Kidney Int,2006; 70(12):1287-1296.
[34]姚素花,王彦,陈凤慧,等.乙酰肝素酶、血管内皮生长因子和核因子-κB在原发性膜性肾病患者肾小球内的表达变化及意义[J].中国美容医学,2012；21(z1)：37-39.
[35]舒同.舒洛地特对糖尿病大鼠肾脏NF-κB、ICAM-1表达的影响及肾保护作用[D].广州,中山大学硕士学位论文,2007.
[36]杜江涛,王建生,赵瑛瑛,等.舒洛地特对糖尿病肾病大鼠肾脏乙酰肝素酶及碱性成纤维细胞生长因子表达影响[J].中华实用诊断与治疗杂志,2011；25(3)：253-254.
[37]廖丹,白云凯,肖欢,等.乙酰肝素酶在慢性肾脏疾病患者肾组织中的表达及其意义[J].国际泌尿系统杂志,2012；32(6)：768-770.
[38]Nosadini R, Velussi M, Broeeo E, et al. Altered transcapillary escape of albumin and microalbuminuria reflects two different pathogenefic mechanisms[J]. Diabetes,2005, 54(1):228-233.
[1]Laluck BJ Jr., Catttran DC. Prognosis after a complete remission in adult patients with idiopathic membranous nephropathy[J]. Am J Kid Dis,1993;33(6):1026-1032
[2]Chen A, Frank R, Vento S, et al. Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome[J]. BMC Nephrol 2007;8:11.
[3]Ponticelli C. Membranous nephropathy[J]. J Nephrol 2007; 20(3):268-87.
[4]Kerjaschki D. Molecular pathogenesis of membranous nephropathy[J]. Kidney Int, 1992; 41 (4):1090-1105.
[5]达展云,崔世维,钱桐荪.Heymann肾炎抗原及免疫复合物的研究进展[J].国外医学·泌尿系统分册.2000；20(增刊)：23—24.
[6]Beck LH Jr, Bonegio RG, I,ambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy[J]. N Engl J Med,2009; 361:11-21.
[7]曲贞,刘刚.特发性膜性肾病发病机制的研究进展[J].临床肾脏病杂志,2012；12(1)：7-8.
[8]Beck LH Jr, Fervenza FC, Beck DM, et al. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy [J]. J Am Soc Nephrol.2011; 22(8):1543-50.
[9]Qin w, Beck LH Jr, Zeng C, et al. Anti -phospholipase A2 receptor antibody in nlenlbranous nephropathy[J]. J Am Soc Nephrol,2011; 22:1137-1143.
[10]周广宇,金玲,于晶,等.成人膜性肾病患者血清抗PLA2R抗体与病情的相关性[J].中华肾脏病杂志,2012；28(2)：111-114.
[11]Stanescu HC, Arcos-Burgos M, Medlar A, et al. Risk HLA-DQAI and PLA(2)R1 alleles in idiopathic membranous nephropathy [J]. N Engl J Med,2011; 364:616-626
[12]Lin YH, Chen CH, Chen SY, et al. Association of phospholipaseA2 receptor 1 polymorphisms with idiopathic membranous nephropathy in Chinese patients in Taiwan[J]. J Biomed Sci,2010;17:81.
[13]Prunotto M Autoimmunity in membranous nephropathy targets aldose reductase and S0D2[J]. J Am Soc Nephrol,2010; 3:507-519.
[14]Stanescu HC, Arcos-Burgos M, Medlar A, et al. Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy [J]. N Engl J Med.2011; 364(7):616-26.
[15]Debiec H, Lefeu F, Kemper MJ,et al. Early-childhood membranous nephropathy due to cationic bovine serum albumin[J]. N Engl J Med,2011; 364(22):2101-10.
[16]Zhang H. Ding J, Fan Q, et al. TRPC6 Up-docyte apoptosis might result from ERK activation and NF-κB translocation[J]. Exp Biol Med,2009; 234(9):1029-1036.
[17]Ohashi T, Uchida K, Yumura W, et al. Membranous glomerulonephritis (membranous nephropathy):pathogenesis, pathophysiology,and therapy [J]. Nippon Rinsho,2006; 64(12): 417-421.
[18]Kuroki A, lyoda M, Shibata T, Sugisaki T. Th2 cytokines increase and stimulate B cells to produce IgG4 in idiopathic membranous nephropathy[J]. Kidney Int,2005;68(1): 302-310.
[19]Kawasaki Y, Suzuki J, Sakai N,et al. Evaluation of T helper-1/-2 balance on the basis of IgG subclasses and serum cytokines in children with glomerulonephritis [J]. Am J Kidney Dis,2004; 44(1):42-9.
[20]Cunningham PN, Quigg RJ. Contrasting roles of complement activation and its regulation in membranous nephropathy[J]. J Am Soc Nephrol.2005; 16(5):1214-22.
[21]Segawa Y, Hisano S, Matsushita M, et al. IgG subclasses and complement pathway in segmental and global membranous nephropathy[J]. Pediatr Nephrol,2010; 25(6): 1091-1099.
[22]Hyun SL. Pathogenic role of TGP-13 in the progression of podocyte diseases[J], Histol Histopatho,2011; 26(1):107-116.
[23]梅长林,刘亚伟.特发性膜性肾病的治疗评价[J].继续医学教育,2006；20(5)：8-11.
[24]Jha V, Ganguli A, Saha TK, et al. A randomized, cortrolled trial of steroids and cyclopho-sphamide in adlts with nephrotic synrome caused by id iopathic embranos nephropathy[J]. J Am SocNephrol,2007; 18(6):1899-1904.
[25]Ponticelli C, Zucchelli P, Passerini P, et al. A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy [J]. Kidney Int,1995; 48 (5):1600-1604.
[26]丛敏,江蓓,胡昭,等.来氟米特治疗原发性肾病综合征的多中心临床观察[J].山东大学学报(医学版),2007；45(3)：295-298.
[27]Wozel G, Pfeiffer C. Leflunomide-a new drug for pharmacological immunomodulation[J]. Hautarzt.,2002; 53(5):309-15.
[28]朱开颜,毕春艳.来氟米特治疗膜性肾病的疗效观察[J].中国实用医药,2009；4(32)：99-100.
[29]熊晓玲.特发性膜性肾病的治疗进展[J].国外医学泌尿系统分册,2004；24(1)：131-133.
[30]Meyrier A. Treatment of glomerular disease with cyclosporine A[J]. Nephrol Dialy Transplant,1989; 4:923
[31]Wetzels JF. Tacrolimus in membranous nephropathy[J]. Kidney Int,2008,73(2):238.
[32]孙广东,许钟镐,罗萍,苗里宁.他克莫司治疗特发性膜性肾病的临床疗效观察[J].中国老年学杂志,2008；28(5)：469-471.
[33]Xie G, Xu J, Ye C, et al. Immunosuppressive Treatment for Nephrotic Idiopath Membranous Nephropathy:A Meta-Analysis Based on Chinese Adults[J]. PLoS One. 2012;7(9):e44330.
[34]刘少军,顾勇,杨海春,等.霉酚酸酯对肾大部切除大鼠肾脏的保护作用[J].中华肾脏病杂志,2002；18：199.
[35]Kobayashi M, Kojima C, Sugiura H, et al. Case of MMF monotherapy for membranous nephropathy[J]. Nihon Jinzo Gakkai Shi,2010; 52(5):572-7.
[36]张翥,张淅涛,马继伟,刘浩飞.吗替麦考酚酯联合小剂量激素治疗膜性肾病的疗效观察[J].中国中西医结合肾病杂志,2012；12(1)：59-60.
[37]Chen Y, Schieppati A, Cai G, et al. Immunosuppression for Membranous Nephropathy:A Systematic Review and Meta-Analysis of 36 Clinical Trials[J]. Clin J Am Soc Nephrol. 2013[Epub ahead of prin].
[38]Fervenza FC, Cosio FG, Erickson SB, et al. Rituximab treatment of idiopathic membranous nephropathy[J]. Kidney Int,2008; 73(1):117-125.
[39]Fervenza FC, Abraham RS, Erickson SB, et al. Rituximab therapy in idiopathic membranousn ephropathy:a 2-year study[J]. Clin J Am Soc Nephrol,2010; 5(12): 2188-2198.
[40]Ruggenenti P, Cravedi P, Chianca A, et al. Rituximab in idiopathic membranous nephropathy [J]. J Am Soc Nephrol.2012; 23(8):1416-25.
[41]章洁,王丹,马恒颢,等.肾局部内皮素与蛋白尿关系的实验骈究[J].中华肾脏病杂志,2000；16(4)：261—262.
[42]Nakamura T, Ebihara I, Fukui M, et al. Effect of a specific endothelinle。receptorA antagonist on mRNA levels for extracellular matrix components an growth factors in diabetic glomeruli[J]. Diabetes,1995,44(8):895-899.
[43]刘志红,李世军,吴燕,等.雷公藤多苷联合小剂量激素治疗特发性膜性肾病前瞻性对照研究[J].肾脏病与透析肾移植杂志,2009；18(4)：303—309.
[44]何志军,马路,潘涛,武强.联合雷公藤多甙片、激素及中草药治疗老年膜性肾病的临床观察[J].临床肾脏病杂志,2012；12(7)：325-326.
[45]秦卫松,刘志红,曾彩虹,等.霄公藤甲素对Heymann肾炎模型足细胞病变的影响[J].肾脏病与透析肾移植杂志,2007；16(2)：101—109.
[46]陈朝红,刘志红,洪亦眉,等.雷公藤甲素干预C5b-9诱导足细胞损伤的体外研究[J].肾脏病与透析肾移植杂志,2009；18(4)：310-317.
[47]Ruggenenti P, Cravedi P, Remuzzi G. Latest treatmentstrategies for membranous nephropathy[J]. Expert Opin Pharmacother,2007; 8(18):3159-3171.