Protective effects and regulatory mechanisms of Shen-shuai-yi recipe on renal fibrosis in unilateral ureteral obstruction-induced mice.

Renal fibrosis (RF) is a common pathological feature of chronic kidney disease (CKD), which remains a major public health problem. As now, there is still lack of chemical or biological drugs to reverse RF. Shen-shuai-yi Recipe (SSYR) is a classical Chinese herbal formula for the treatment of CKD. However, the effects and mechanisms of SSYR in treating RF are still not clear. In this study, the active constituents SSYR for treating RF were explored by UHPLC-Q-Orbitrap HRMS. Bioinformatics analyses were employed to analyze the key pharmacological targets and the core active constituents of SSYR in the treatment of RF. In experimental validation, vehicle or SSYR at doses of 2.12 g/kg/d and 4.25 g/kg/d were given by orally to unilateral ureteric obstruction (UUO) mice. 13 days after treatment, we detected the severity of renal fibrosis, extracellular collagen deposition and pre-fibrotic signaling pathways. Bioinformatics analysis suggested that signal transducer and activator of transcription 3 (STAT3) was the core target and lenticin, luteolin-7-O-rutinoside, hesperidin, kaempferol-3-O-rutinoside, and 3,5,6,7,8,3′,4′-heptamethoxyflavone were the key constituents in SSYR for treating RF. SSYR significantly reduced the expressions of fibronectin (FN), α-smooth muscle actin (α-SMA), collagen-I and alleviated renal interstitial collagen deposition in UUO kidneys. In mechanism, SSYR potently blocked the phosphorylation of STAT3 and Smad3 and suppressed the expression of connective tissue growth factor (CTGF). Collectively, SSYR can ameliorate RF inhibiting the phosphorylation of STAT3 and its downstream and reducing the collagen deposition, suggesting that SSYR can be developed as a novel medicine for treating RF.

The roles of serine hydrolases and serum albumin in alisol B 23-acetate hydrolysis in humans.

lisol B 23-acetate (AB23A), a major bioactive constituent in the Chinese herb Zexie (), has been found with multiple pharmacological activities. AB23A can be readily hydrolyzed to alisol B in mammals, but the hydrolytic pathways of AB23A in humans and the key enzymes responsible for AB23A hydrolysis are still unrevealed. This study aims to reveal the metabolic organs and the crucial enzymes responsible for AB23A hydrolysis in human biological systems, as well as to decipher the impact of AB23A hydrolysis on its biological effects. The hydrolytic pathways of AB23A in human plasma and tissue preparations were carefully investigated by using Q-Exactive quadrupole-Orbitrap mass spectrometer and LC-UV, while the key enzymes responsible for AB23A hydrolysis were studied via performing a set of assays including reaction phenotyping assays, chemical inhibition assays, and enzyme kinetics analyses. Finally, the agonist effects of both AB23A and its hydrolytic metabolite(s) on FXR were tested at the cellular level. AB23A could be readily hydrolyzed to form alisol B in human plasma, intestinal and hepatic preparations, while human butyrylcholinesterase (hBchE) and human carboxylesterases played key roles in AB23A hydrolysis in human plasma and tissue preparations, respectively. It was also found that human serum albumin (hSA) could catalyze AB23A hydrolysis, while multiple lysine residues of hSA were covalently modified by AB23A, suggesting that hSA catalyzed AB23A hydrolysis its pseudo-esterase activity. Biological tests revealed that both AB23A and alisol B exhibited similar FXR agonist effects, indicating AB23A hydrolysis did not affect its FXR agonist effect. This study deciphers the hydrolytic pathways of AB23A in human biological systems, which is very helpful for deep understanding of the metabolic rates of AB23A in humans, and useful for developing novel prodrugs of alisol B with desirable pharmacokinetic behaviors.

Elucidating a fresh perspective on the interplay between exosomes and rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by chronic synovitis and the destruction of bones and joints. Exosomes are nanoscale lipid membrane vesicles originating from multivesicular bodies and are used as a vital means of intercellular communication. Both exosomes and the microbial community are essential in RA pathogenesis. Multiple types of exosomes from different origins have been demonstrated to have effects on various immune cells through distinct mechanisms in RA, which depend on the specific cargo carried by the exosomes. Tens of thousands of microorganisms exist in the human intestinal system. Microorganisms exert various physiological and pathological effects on the host directly or through their metabolites. Gut microbe-derived exosomes are being studied in the field of liver disease; however, information on their role in the context of RA is still limited. Gut microbe-derived exosomes may enhance autoimmunity by altering intestinal permeability and transporting cargo to the extraintestinal system. Therefore, we performed a comprehensive literature review on the latest progress on exosomes in RA and provided an outlook on the potential role of microbe-derived exosomes as emerging players in clinical and translational research on RA. This review aimed to provide a theoretical basis for developing new clinical targets for RA therapy.

LncRNA NEAT1 Promotes High Glucose-Induced Mesangial Cell  Hypertrophy by Targeting miR-222-3p/CDKN1B Axis.

Glomerular hypertrophy is an early morphological alteration in diabetic nephropathy. Cyclin-Dependent Kinases have been shown to be required for high glucose (HG)-induced hypertrophy; however, the upstream regulators of CDKN1B in glomerular hypertrophy remain unclear. Herein we describe a novel pathway in which Long noncoding RNA (lncRNA) NEAT1 regulates the progression of mesangial cell hypertrophy via a competing endogenous RNA (ceRNA) mechanism. Real-time PCR was performed to detect the relative NEAT1 and miR-222-3p expressions and further confirmed the relationship between NEAT1 and miR-222-3p. Cell cycle was evaluated by flow cytometry. The related mechanisms were explored by Western blot, RNA immunoprecipitation and chromatin immunoprecipitation assay. We show that NEAT1 forms double stranded RNA (dsRNA) with miR-222-3p, thus limiting miR-222-3p’s binding with CDKN1B. This release of CDKN1B mRNA leads to elevated CDKN1B protein expression, resulting in hypertrophy. In addition, we demonstrated that STAT3 which is activated by HG induces the transcription of NEAT1 by binding to its promoter. Our findings underscore an unexpected role of lncRNAs on gene regulation and introduce a new mode of proliferation regulation in mesangial cells.

Mechanism research of Bu-Shen-Huo-Xue formula against renal fibrosis in rats with 5/6 nephrectomy via E-cadherin, α-SMA, and TGF- β 1, Clinical Nephrology

OBJECTIVE:Renal fibrosis generally results in renal failure during the end stage of chronic renal diseases. There are many cell factors including E-cadherin, α-SMA, and TGF-β1 influencing deposition of extracellular matrix and leading to renal fibrosis. As the most important and widely-used therapy for various diseases in China for thousands of years, traditional Chinese medicine (TCM) provides a novel treatment for renal fibrosis. For clinical application, we explore the effect of Bu-Shen-Huo-Xue formula (BSHX), a traditional Chinese herbal formula, on E-cadherin and α-SMA in rats with 5/6 nephrectomy.

MATERIALS AND METHODS:Sprague-Dawley rats were subjected to 5/6 nephrectomy to induce chronic renal failure (CRF); they were divided into three groups including a CRF control group, a BSHX group, and a Cozaar group, and compared with a normal control group. After 8 weeks of therapy with the respective drug, E-cadherin, α-SMA, and TGF were detected by immunohistochemistry assays in renal tissues.

RESULTS:As the immunohistochemistry assays indicated, BSHX could significantly enhance the expression of E-cadherin and depress the levels of α-SMA and TGF-β1 expression in rats’ renal tissues with 5/6 nephrectomy.

CONCLUSION:BSHX can effectively relieve the renal fibrosis in rats with 5/6 nephrectomy via the change of cell factor levels including enhancement of the expression of E-cadherin and depression of the levels of α-SMA and TGF-β1 expression.

作者：

邵长鑫1,2林欢欢1,2靳晓杰1,2李越峰1,2刘永琦3,4姚娟1,2

摘要：

黄芪Astragali Radix具有补气固表、利尿托毒、排脓、敛疮生肌之功效，为临床常用补气药。其临床应用广泛，在中医古籍中有多种黄芪炮制品的使用记载，如米黄芪、酒黄芪、盐黄芪、蜜黄芪等，而沿用至今的炮制品主要为生黄芪和炙黄芪。现代研究表明黄芪主要化学成分为多糖类、皂苷类、黄酮类成分，具有抗炎、抗氧化、抗肿瘤、增强免疫等作用。通过对本草专著、中医古籍及炮制规范等文献资料进行查阅分析，梳理古籍文献中有关黄芪功效主治、炮制沿革等方面的论述，并对黄芪炮制工艺、化学成分、药理作用等现代科研成果进行综述，为黄芪的相关研究提供参考。

关键词：

黄芪; 炮制; 历史沿革; 化学成分; 功效; 药理作用;

专辑：

医药卫生科技

专题：

中药学

分类号：

R283

原始文档：

廖琳1孙永康2胡静1陈杰1张传富1刘文瑞1徐启明3施倩1路建饶2

1. 上海中医药大学附属第七人民医院肾病科2. 上海中医药大学附属第七人民医院超声科3. 上海中医药大学

摘要：目的 探析超声引导下激光消融(laser ablation, LA)治疗难治性继发性甲状旁腺功能亢进(secondary hyperparathyroidism, SHPT)的近期疗效。方法 采用随机数表法将上海中医药大学附属第七人民医院肾病科2019年1月—2020年12月收治的60例难治性SHPT患者分为激光消融(LA)组和甲状旁腺切除术(parathyroidectomy, PTX)组，每组30例。通过VAS评分法比较两组患者术前和术后1周、1个月、3个月、6个月主要临床症状的改善情况，测定两组患者术前和术后1 d、1周、1个月、3个月、6个月血清全段甲状旁腺激素(iPTH)、血清Ⅰ型胶原羧基端肽β特殊序列(β-CTX)、血清总Ⅰ型胶原氨基端延长肽(TP1NP)、血钙、血磷水平，统计两组患者手术时间、住院时间，以及神经损伤、低钙血症等并发症发生情况。结果 两组患者术后1周、1个月、3个月、6个月时皮肤瘙痒、骨痛、失眠、肌无力的VAS评分均较同组术前显著降低(P值均<0.05),PTX组术后1周时皮肤瘙痒、骨痛的VAS评分均较LA组同时间点显著降低(P值均<0.05)。两组患者术后1 d、1周、1个月、3个月、6个月的血钙、血磷、血清iPTH、血清TP1NP、血清β-CTX水平均较同组术前显著降低(P值均<0.05),PTX组术后1 d、1周的血钙、血磷、血清TP1NP水平均较LA组同时间点显著降低(P值均<0.05)。LA组手术时间、住院时间均显著短于PTX组(P值均<0.05),低钙血症和总体并发症的发生率均显著低于PTX组(P值均<0.05)。结论 超声引导下LA治疗SHPT近期疗效与PTX相当，两者均能有效改善患者的临床症状和有关实验室指标水平，但LA住院时间更短，术后并发症发生率更低，其远期疗效有待进一步观察。

关键词：超声; 激光消融术; 继发性甲状旁腺功能亢进; 骨代谢;

基金资助：上海市浦东新区卫生健康委员会卫生计生科研项目(PW2019A-19)； 上海市第七人民医院“启明星”人才培养计划(QMX2019-02)；

DOI：10.19842/j.cnki.issn.0253-9934.2022.12.006

专辑：医药卫生科技

专题：临床医学;内分泌腺及全身性疾病

分类号：R445.1;R582.1

Content retrieved from: https://kns.cnki.net/kcms2/article/abstract?v=RyaFSLOYMk6KnTOI_Lsn8ydgX8g3IAkUV4dYJyrOE6uwwm5Lp62xLGYgJtWy5-W9sZKyrNEpS_9s3NU8WhR_026JYFh972u1bX2S2gYhwNA7rUlkveiWNpinLbp2SIDaU_V-sy-tN9ecvaw1Cve4aw==&uniplatform=NZKPT&language=CHS.

廖琳 路建饶 陈杰 陈晛 胡静 张传富 韩海燕 郭玥

上海中医药大学附属第七人民医院肾病科
摘要：目的探讨不同钙浓度的透析液在老年维持性血透(maintenance hemodialysis,MHD)伴动力缺失性肾性骨病(renal osteodystrophy,ROD)患者治疗中的效果差异。方法选取2017年2月至2019年12月本院收治的老年MHD伴动力缺失性ROD患者96例,采用随机数字表法分为A组(含钙1.25 mmol/L的透析液)、B组(含钙1.50 mmol/L的透析液)各48例,两组患者均连续性实施透析治疗12个月。结果治疗后,A组患者的血钙、血磷低于B组(P<0.05),iPTH、骨密度T值高于B组(P<0.05);A组患者的IMT、RI、IVRT测定值均低于B组(P<0.05),E/A高于B组(P<0.05)。结论含钙1.25 mmol/L的透析液在老年MHD伴动力缺失性ROD患者治疗中对于调节患者血钙、血磷代谢、甲状旁腺素、颈动脉硬化、骨代谢等方面具有积极作用。

关键词：钙; 透析液; 老年; 维持性血透; 肾性骨病;

基金资助：上海中医药大学附属第七人民医院人才培养计划项目(编号:QMX2019-02)； 上海市浦东新区卫生健康委员会卫生计生科研项目(编号:PW2019A19)；

专辑：医药卫生科技

专题：临床医学;泌尿科学

分类号：R692.5

Content retrieved from: https://kns.cnki.net/kcms2/article/abstract?v=RyaFSLOYMk7Zdlxl38RTdZCi-14Cg-diaMhjEe8Pn12xQWJKEyeKNN1YOKhIXIi0lDGIBoxbTRE02W5t-QbodlR-hqA3k5IWNWm1L5CpT6BvM9x7fF0eoYZ1a4tedqW8Zz2R-1i6uha3PZnbuEZ3FA==&uniplatform=NZKPT&language=CHS.

廖琳1胡静1孙永康2陈杰1施倩2路建饶1

1. 上海中医药大学附属第七人民医院肾病科2. 上海中医药大学附属第七人民医院超声医学科

摘要：目的 对比药物、超声引导下激光消融术及甲状旁腺全切+前臂移植术（TPTX+AT）治疗维持性血液透析（MHD）并发难治性继发性甲状旁腺功能亢进（SHPT）的临床疗效。方法 选择接受MHD治疗的尿毒症并发难治性SHPT患者60例，按随机数字表法分为药物组、手术1组、手术2组各20例。药物组予西那卡塞联合小剂量骨化三醇治疗，手术1组予超声引导下激光消融术治疗，手术2组予TPTX+AT治疗。分别于治疗前及治疗1周、1个月、3个月、6个月、12个月，采用视觉模拟评分法（VAS）评价患者主要症状，用肾病相关生活质量量表（KDTA）评分评价患者生活质量，检测血红蛋白（Hb）、血清白蛋白（Alb）、钙、磷、血清全段甲状旁腺激素（iPTH），采用多普勒超声测定颈动脉内膜中层厚度（IMT）、颈动脉阻力指数（RI）。统计手术1组、手术2组的手术时间、住院时间，观察并发症发生情况。结果 治疗1、3、6、12个月，药物组VAS、KDTA评分较治疗前改善（P均<0.05），但改善程度低于手术1组、手术2组（P均<0.05）；手术1组、手术2组从治疗1周及1、3、6、12个月VAS、KDTA评分较治疗前改善（P均<0.05），但两组间各时间点VAS、KDTA评分比较差异无统计学意义（P均>0.05）。治疗1、3、6、12个月，手术1组、手术2组Hb、Alb较治疗前升高，且高于药物组（P均<0.05）；手术1组与手术2组各时间点Hb、Alb比较差异无统计学意义（P均>0.05）。治疗3个月后，药物组血钙、磷、iPTH逐渐下降，与治疗前比较差异有统计学意义（P均<0.05）。治疗1周，手术1组、手术2组血钙、磷、iPTH迅速下降，治疗1个月开始上升，治疗3个月趋于稳定，但均低于术前及药物组（P均<0.05）；其中治疗1周，手术2组血钙、iPTH低于手术1组（P均<0.05）。治疗前、治疗6个月三组IMT、RI比较差异均无统计学意义（P均>0.05）；治疗12个月，手术1组、手术2组IMT、RI均较治疗前下降，但药物组IMT、RI较治疗前升高，手术1组、手术2组IMT、RI低于药物组（P均<0.05）。手术1组手术时间、住院时间短于手术2组（P均<0.05）。药物组低钙血症发生率低于手术1组、手术2组（P均<0.05）；手术1组出现声音沙哑2例、手术2组出现声音沙哑3例，两组比较差异无统计学意义（P>0.05）。治疗期间三组均无严重不良反应发生。结论 三种方法均能有效治疗MHD并发SHPT。但药物治疗起效慢，短期疗效不如甲状旁腺全切+前臂移植手术；超声引导下激光消融术更适用于心肺功能差、不能耐受全身麻醉的患者。

关键词：继发性甲状旁腺功能亢进; 尿毒症; 维持性血液透析; 西那卡塞; 超声引导下激光消融术; 甲状旁腺切除术; 前臂移植术;

基金资助：上海市浦东新区卫计委面上项目（PW2019A-19）； 上海市第七人民医院“启明星”培养计划（QMX2019-02）；

专辑：医药卫生科技

专题：临床医学;内分泌腺及全身性疾病;泌尿科学

分类号：R692.5;R582.1

Content retrieved from: https://kns.cnki.net/kcms2/article/abstract?v=RyaFSLOYMk6YRmde1pHnHStZJBAZMbGP5mVuKs_kBAT2R4SHE5sd1qvVYmdEXO4ugKFKNXiRQ5LBBmPqs4eiaTY2PZQRS5EKFXz-LL9JO1__x4A33z4rHRa3SU-WcE3CoLfW5pDmweyjKQ0hp-Et0Q==&uniplatform=NZKPT&language=CHS.

翁涛涛1刘伟2葛广波3胡静1

1. 上海中医药大学附属第七人民医院肾病科2. 上海中医药大学附属曙光医院,肝病研究所上海市中医临床重点实验室,肝肾疾病病证教育部重点实验室3. 上海中医药大学交叉科学研究院

<正>近年来慢性肾脏病(chronic kidney disease, CKD)在全球的发病率和死亡率明显上升[1,2]。截止到2017年，全球CKD人数达6.975亿，其中中国达1.323亿，是全球最多的国家[3]。目前，CKD已被确认为世界范围内危害人类健康的主要公共卫生问题之一。肾纤维化(renal fibrosis, RF)是CKD向终末期肾脏病(end-stage renal disease, ESRD)发展的共有病理变化，基金资助：

“七院名中医”人才培养计划项目(No.MZY2021-01)； “七院工匠”人才培养计划项目(No.GJ2021-06)； 上海浦东新区中医专病品牌倍增计划-慢性肾病专病(No.PDZY-2021-0302)；

专辑：医药卫生科技

专题：泌尿科学

分类号：R692

Content retrieved from: https://kns.cnki.net/kcms2/article/abstract?v=RyaFSLOYMk7D52rJ3hl_0GpSwG8didqVln0Bb6sStdLmtulPTX6UdPYqRlpbjT0D1gz-JbXRRUSO4D43qnx3mgyAElPaTGfASXDCzSP4cjtbb7zxgEopICLbHoIaQzRIBgA7YumQD3xzgoHWnwTmxw==&uniplatform=NZKPT&language=CHS.

• Pierre Ronco1,2,
• Laurence Beck3,
• Hanna Debiec1,
• Fernando C. Fervenza  ORCID: orcid.org/0000-0002-9952-209X4,
• Fan Fan Hou  ORCID: orcid.org/0000-0003-3117-74185,
• Vivekanand Jha  ORCID: orcid.org/0000-0002-8015-94706,7,8,
• Sanjeev Sethi  ORCID: orcid.org/0000-0002-4536-77099,
• Allison Tong10,11,
• Marina Vivarelli12 &
• …
• Jack Wetzels  ORCID: orcid.org/0000-0002-0650-692113

Show authors

Nature Reviews Disease Primers volume 7, Article number: 69 (2021) Cite this article

Subjects

• Autoimmunity

Membranous nephropathy

Abstract

Membranous nephropathy (MN) is a glomerular disease that can occur at all ages. In adults, it is the most frequent cause of nephrotic syndrome. In ~80% of patients, there is no underlying cause of MN (primary MN) and the remaining cases are associated with medications or other diseases such as systemic lupus erythematosus, hepatitis virus infection or malignancies. MN is an autoimmune disease characterized by a thickening of the glomerular capillary walls due to immune complex deposition. Identification of the phospholipase A2 receptor (PLA2R) as the major antigen in adults in 2009 induced a paradigm shift in disease diagnosis and monitoring and several other antigens have since been characterized. Disease outcome is difficult to predict and around one-third of patients will undergo spontaneous remission. In those at high risk of progression, immunosuppressive therapy with cyclophosphamide plus corticosteroids has substantially reduced the need for kidney replacement therapy. Owing to carcinogenic risk, other treatments (calcineurin inhibitors and CD20-targeted B cell depletion therapy (rituximab)) have been developed. However, disease relapses are frequent when calcineurin inhibitors are stopped and the remission rate with rituximab is lower than with cyclophosphamide, particularly in patients with high PLA2R antibody titres. Other new drugs are already available and antigen-specific immunotherapies are being developed.

Introduction

Membranous nephropathy (MN) is a pathologically defined disorder of the kidney glomerulus. The specific lesion is an apparent thickening of the glomerular capillary walls, which results from immune complex formation on the outer aspect of the basement membrane1. The immune deposits consist of immunoglobulin G (IgG), the relevant antigens and complement components, including the membrane attack complex (MAC). The consequence of the immunological conflict is the loss of large amounts of proteins in the urine (proteinuria), which is predominantly mediated by the pathophysiological disturbance of the podocyte structure caused by immune complex deposition and MAC formation. Patients experience a decrease in serum albumin levels and generalized oedema, which define a condition called nephrotic syndrome. Most patients report fatigue as an important symptom. MN accounts for ~30% of cases of nephrotic syndrome in adults and is only surpassed in prevalence among nephrotic non-diabetic glomerular diseases by podocytopathy presenting as focal and segmental glomerulosclerosis lesions in some populations (African and Hispanic American individuals). In ~80% of patients, there is no underlying cause of MN (primary MN (pMN)) and 20% are associated with medications, such as NSAIDs, or other diseases (secondary MN (sMN)) such as lupus (also referred to as systemic lupus erythematosus (SLE)), hepatitis B or hepatitis C, and malignancies1.

Patient outcomes are variable. For a long time, outcome was governed by the rule of thirds, with a third of the patients undergoing spontaneous remission, a third keeping variable levels of proteinuria and the remaining third progressing to advanced kidney failure. However, immunosuppressive therapy has substantially reduced the rate of kidney replacement therapy, which is ~10% with cyclophosphamide treatment but is not yet established for other newer agents such as rituximab1.

Substantial advances in the understanding of MN pathophysiology have occurred in the past two decades, starting with the identification of neutral endopeptidase (NEP), the first discovered human podocyte antigen, which is involved in a rare subset of patients with neonatal allo-immune MN2. This finding paved the way for the characterization of the M-type phospholipase A2 receptor (PLA2R) as another podocyte antigen in 2009. Antibodies to PLA2R are specific for MN and found in ~70% of adult patients with the disease3. This discovery demonstrated that pMN is an autoimmune disease in which the podocyte is both the target of circulating auto-antibodies and probably the main source of the auto-antigen. It induced a paradigm shift in thinking about establishing diagnosis (possibly without a kidney biopsy), predicting outcome and monitoring treatment in patients with pMN, including after transplantation. This discovery resulted in the rapid development of reliable assays for PLA2R antibodies and pMN can be considered as a model of organ-specific autoimmune disease and of personalized medicine. Subsequently, another podocyte antigen, thrombospondin type 1 domain-containing 7A (THSD7A) was identified4. THSD7A accounts for <5% of pMN4.

Owing to the technological advances in combining laser microdissection of glomeruli and mass spectrometry of solubilized digested proteins, several further antigens have been identified such as exostosin 1 (EXT1) and EXT2, protein kinase C-binding protein NELL1 (also known as neural epidermal growth factor like 1 protein), semaphorin 3B (SEMA3B), neural cell adhesion molecule 1 (NCAM1), protocadherin 7 (PCDH7) and serine protease HTRA1 (refs5,6). These antigens, like PLA2R and THSD7A, can be associated with pMN or with a specific ‘cause’ of sMN, such as lupus, other autoimmune disease or cancer, recognizing that the link of causality is not established in many instances. The discovery of different antigens therefore challenges the classification that opposes pMN to sMN and leads to a discussion of an antigen-based classification in which each antigen-associated MN would have its specific immunological profile (IgG subclass), pattern of associated diseases and outcome. Future studies should evaluate whether management should be driven by the antigen specificity as is the case for PLA2R-associated MN, in which positive serology now replaces kidney biopsy and quantitative assessment of PLA2R antibody levels is helpful in predicting response to therapy. Within the coming few years, similar steps forward can be expected for the other antigens (although they are rarer and large patient cohorts will not be recruited). Thus, in this Primer, we adhere to the current nomenclature of pMN and sMN, while being mindful that it will need to be adapted based on evidence from future studies.

Despite these advances, treatment of MN remains controversial. For a long time, cyclophosphamide-based regimens were the standard of care as they have been shown to prevent the occurrence of advanced kidney failure; however, they expose patients to an increased risk of malignancy1,7. Treatment with calcineurin inhibitors (CNIs), such as cyclosporine or tacrolimus, induces a high rate of remission but with a high rate of relapse and renal toxic effects are a concern in prolonged treatment1,7. Therapy protocols with CD20-targeted agents, such as rituximab, are well tolerated but only 60–70% of patients reach persistent clinical remission compared with ~80% for cyclophosphamide and their efficacy in preventing kidney disease progression has not yet been proven1,7. Randomized controlled trials (RCTs) published in the past few years (GEMRITUX8, MENTOR9, STARMEN10 and RI-CYCLO11) have not clarified the dilemma between cyclophosphamide (more toxic) and CD20-targeted therapy (less efficient in the protocols used), which calls for new therapeutic approaches. The lack of RCTs with sufficient statistical power that directly compare these two treatments is a major reason for the enduring uncertainty. Furthermore, the dosage of rituximab is important to consider when effectivity is studied.

In this Primer, we summarize current knowledge of the epidemiology of MN and highlight the major advances that have led to a better understanding of MN pathophysiology, diagnosis and improved patient care. We also identify the major gaps in current knowledge and provide recommendations on how to improve long-term renal prognosis and quality of life.

Epidemiology

Incidence, prevalence and natural history

MN occurs in all regions and all ethnicities. The data on the incidence of MN and MN subtypes remain quite limited as large population-based studies that are representative across diverse international populations are not available. The annual incidence rates of MN are estimated at 10–12 per million in North America and 2–17 per million in Europe7,12,13,14,15. The disease affects individuals of all ages with a mean age of diagnosis at 50–60 years16 and a 2:1 male predominance for unknown reasons17. Whether incidence rates of MN vary between regions or ethnicities remains unclear as most data are from North America and Europe.

pMN is the most common cause of idiopathic nephrotic syndrome in non-diabetic adults worldwide, accounting for 20–37% in most kidney biopsy series and increasing to as high as 58% in adults >65 years of age7,18,19. MN is uncommon in children, accounting for <7% of biopsies13,20,21,22,23,24, and is often associated with other diseases such as hepatitis B24. The percentage of PLA2R-associated MN in adolescents is similar to that of adults.

No good data are available on the prevalence of the various aetiologies of sMN1,25. The main reason is that the epidemiology has varied with time, with infectious causes, such as hepatitis, strongly decreasing with vaccination, whereas others, such as lupus and drug exposure, are increasing.

In some regions, a temporal change in prevalence of MN has been reported18,26,27. A study in China analysed data from kidney biopsy samples of 71,151 patients in 938 hospitals in 282 cities taken over 11 years (2004–2014) encompassing all age groups17. The prevalence of MN increased by 13% annually, whereas the proportions of other major glomerulopathies remained stable. Areas with higher levels of fine particulate matter with diameters ≤2.5 µm (PM2.5) air pollution had the highest rates of MN. In areas with PM2.5 levels >70 μg/m3, each 10 μg/m3 increase in PM2.5 concentration was associated with 14% higher odds for MN. This association was subsequently confirmed by another study in China28. However, whether the increase of MN is connected to a PLA2R-driven mechanism remains unclear as serum PLA2R antibody levels were not measured in most patients in these studies and whether air pollution is a causative risk of MN requires further confirmation.

The natural history of untreated MN has been reported with spontaneous complete remission rates of 20–30% and 10-year renal survival rates of 60–80% in most studies29,30,31. Despite its ‘benign’ presentation characteristics, MN has, for a long time, remained the second or third leading cause of kidney failure among the primary glomerulonephritis types in the USA and Europe32. In patients who continue to have nephrotic syndrome, kidney failure develops in 40–50% over a period of 10 years33. These patients are also at an increased risk of life-threatening thromboembolic and cardiovascular events34.

Genetic factors

MN is not a typical hereditary disease in Mendelian terms but there is growing evidence to support a strong genetic component. Like most autoimmune diseases, MN has a strong association with the class II antigens of the human leukocyte antigen (HLA) system that are encoded by the relevant alleles of the HLA-D locus on chromosome 6. HLA class II molecules are involved in the regulation of immune responses: their expression is mostly limited to antigen-presenting cells, such as B cells, monocytes, macrophages, dendritic cells and Langerhans cells of the skin, and their role is to present peptide antigens to the immune system. Thus, they are associated with autoimmune diseases. It has been known since 1979 and 1989 that MN is strongly associated with HLA-DR3 and HLA-DQA1, respectively, in Caucasian populations35,36. An initial genome-wide association study conducted in three European cohorts including 556 patients of white ancestry found that pMN in adults was strongly correlated with risk alleles in HLA-DQA1 (chromosome 6) and in PLA2R1 (chromosome 2)37. In individuals who were homozygous for the lead risk alleles, the risk of having MN was nearly 80-fold higher than in those who had neither risk allele. Interestingly, the risk allele that is most significantly associated with pMN is localized in an intron of the gene; thus, this allele is not expected to change PLA2R antigen auto-reactivity. Further studies did not detect mutations or rare variants in the sequence and the splice sites of PLA2R1 (ref.38). Thus, it is unlikely that the immune reaction is triggered by a change in antigen sequence or conformation. It is more probable that post-translational modifications or increased expression of PLA2R antigen in podocytes or other cells have an important role.

A similar strong correlation between risk alleles of PLA2R1 and HLA-DQA1 and the risk of developing MN was found in a large Chinese cohort that included 1,112 patients with pMN and 1,020 healthy individuals39. Patients with both risk alleles had an >11-fold increased risk of developing MN. The presence of risk alleles was also correlated to PLA2R antibodies.

Two studies performed in Chinese cohorts revealed different HLA class II alleles associated with an increased risk of MN40,41 and proposed that HLA associations may differ between ethnicities. This was corroborated in the largest international genetic study of MN performed to date. The study involved cohorts from East Asia (1,632 biopsy specimen-diagnosed cases and 3,209 controls) and of European ancestry (2,150 biopsy specimen-diagnosed cases and 5,829 controls) and found ethnic differences in HLA locus associations, defining DRB1*1501 as a major risk allele in East Asian individuals, DQA1*0501 in European individuals and DRB1*0301 in both ethnicities42. The PLA2R1 locus presented the most strongly associated non-HLA signals. In addition, two previously unreported loci, NFKB1 and IRF4, which are both linked to inflammatory pathways, were identified. Genome-wide association study loci account for 32% and 25% of disease risk in East Asian and European individuals, respectively.

In addition to their likely role of presenting PLA2R antigen to the immune system, HLA-D alleles may also be modifiers of MN. Although DRB1*1501 is a major risk allele for the disease, DRB1*1502, which differs from DRB1*1501 by a single amino acid, is not. However, DRB1*1502 has a strong predictive value when associated with HLA risk alleles, being associated with a lower estimated glomerular filtration rate (GFR) and a higher risk of kidney failure43. No data are available concerning genetic predisposition for the other antigens or sMN.

Mechanisms/pathophysiology

In the past 20 years, considerable advances have occurred in the understanding of the pathophysiology of MN with the description of the first podocyte antigens in neonatal2 and adult3 MN. These discoveries revealed the central role of the podocyte in MN pathogenesis. This section describes the classical antigens NEP, PLA2R and THSD7A, the newly reported potential antigens, the autoimmune reactions that lead to the development of antibodies, and the downstream events that lead to nephropathy.

Antigens

NEP

In the 1970s, studies in the Heymann nephritis rat model of MN established the basis of MN pathophysiology. The studies showed that rats express megalin both in the proximal tubular brush-border and in podocytes and that actively or passively introduced megalin antibodies induced the aggregation of immune complexes at the basal surface of podocytes. This observation has led to the concept that a podocyte antigen, megalin (now called LRP2), could serve as a target of circulating antibodies leading to the in situ formation of immune complexes44,45,46. In humans, where megalin is not or only weakly present on podocytes36,47 and cannot therefore be the target of circulating antibodies, NEP was identified in 2002 as the responsible antigen in a subset of patients with allo-immune antenatal MN2. In this rare condition, mothers carry a homozygous or compound heterozygous nonsense mutation in MME (encoding NEP), which results in the absence of the protein48 (Fig. 1). During pregnancy, they become immunized to the paternally inherited NEP in the placenta and the resulting maternal IgG antibodies are then transferred to the fetus, which is not NEP-deficient and therefore develops active disease.

Fig. 1: Fetomaternal allo-immune glomerulopathy caused by maternal anti-NEP antibodies.

Antenatal membranous nephropathy is the result of a homozygous or compound heterozygous nonsense mutation in MME (encoding neutral endopeptidase (NEP)) in the pregnant mother, which results in the absence of NEP. The MME–/– pregnant mother develops allo-imunization against NEP that is expressed by the placenta (via paternal inheritance to the fetus) and recognized as a non-self protein by the mother’s immune system. In the third trimester of pregnancy, NEP antibodies are transferred to the MME+/– fetus and bind to the NEP antigen expressed on podocytes of the fetus, who develops active disease. NEP IgG1 antibodies bind to epitopes on NEP and activate the classical complement pathway through binding of complement component C1q to the NEP IgG1 antibodies, leading to the formation of C5b–9 (membrane attack complex of complement (MAC)). MAC insertion into the podocyte membrane induces cell damage. No podocyte damage occurs in fetuses from mothers producing only IgG4, which does not bind C1q and therefore fails to activate the complement cascade.

NEP is a membrane-bound zinc-dependent endopeptidase and is involved in the catabolism of regulatory peptides with vasoactive properties49,50. NEP is expressed in numerous tissues and its membrane form is naturally present on human podocytes at the sole of their foot processes51. Maternal production of complement-fixing NEP IgG1, which also inhibits NEP enzyme activity, is necessary for the disease to develop52. This suggests that some toxic effects of NEP antibodies may be associated with alterations of glomerular haemodynamics, endothelial permeability or tubular function. Analysis of these very rare cases strongly supports the idea that the circulating antibodies react with an intrinsic component of the podocyte membrane. Moreover, these observations suggest that similar truncating mutations of other podocyte antigens could lead to allo-immunization and renal disease in infants.

PLA2R

PLA2R is the most frequently targeted auto-antigen in MN (up to 80% of pMN cases) (Table 1). The antigen was initially identified by mass spectrometric analysis of an electrophoretic gel band that corresponded to a glycoprotein recognized by serum from patients with idiopathic (primary) MN but not by serum from patients with proteinuria or healthy controls3. PLA2R is a transmembrane glycoprotein abundantly expressed by the human podocyte3, present at the level of the foot process as well as on the apical surface, where it can be shed into the urine in vesicular structures during disease53. Its specific role in the glomerulus is not known. As some small mammals lack constitutive podocyte PLA2R expression, PLA2R may not be essential to podocyte function. Initially identified as a receptor for secreted phospholipase A2 enzymes54, PLA2R might bind and internalize these small and potentially toxic enzymes that pass through the glomerular basement membrane (GBM). The extracellular domain of PLA2R comprises 10 domains: an N-terminal cysteine-rich (CysR) domain, a fibronectin 2 domain and eight C-type lectin-like domains (CTLD) that harbour distinct humoral epitopes.

Table 1 Established and new and putative antigens in membranous nephropathy

The auto-antibodies that form against PLA2R initially target the N-terminal immunodominant CysR region and a short amino acid sequence in this domain has been shown to stimulate the production of very high-affinity antibodies55. In most patients, epitope spreading and the production of antibodies to distal regions of the extracellular domain occurs, including CTLD1, CTLD7 and CTLD8 (refs56,57). The detection of epitope spreading in a patient seems to confer an inferior prognosis compared with individuals who have CysR antibodies only58, although this notion has been challenged57. The predominant antibodies to PLA2R are of the IgG4 subclass but other subclasses, such as IgG1 and IgG3, are present in lower amounts3,59. Quantification of the overall titre of PLA2R antibodies has been a useful tool in monitoring the immune response to therapy in PLA2R-associated MN13 and the decline and disappearance of PLA2R antibodies has been termed immunological remission and precedes and predicts clinical remission.

THSD7A

Thrombospondin type 1 domain-containing 7A (THSD7A) is a multidomain transmembrane glycoprotein expressed by the podocyte that serves as an auto-antigen in 2–3% of patients with MN60. Similar to PLA2R, it was identified by performing mass spectrometry on native, deglycosylated or proteolysed protein bands detectable by human auto-antibodies. Its presence in the glomerulus had not been demonstrated before its discovery as an MN target antigen, although it is now recognized as a conserved basal component of the podocyte, localizing directly between the slit diaphragm and the GBM61. No immunodominant epitope has been discovered and auto-antibodies seem to target multiple regions of the protein, including the N terminus62. Several cases of THSD7A-associated MN have been found in which a malignancy overexpresses THSD7A and may initiate the immune response that then causes MN in the kidney63,64. There are fewer data on using THSD7A antibodies than on PLA2R antibodies for monitoring of disease but THSD7A antibodies, similar to PLA2R antibodies, tend to decline with immunosuppressive treatment and their disappearance is associated with eventual clinical remission.

New and putative antigens

Laser microdissection of glomeruli followed by mass spectrometry has been used to identify novel antigens in MN65. The basic premise in the identification of an antigen is that the novel antigen has accumulated in the glomeruli (immune deposits) compared with other proteins and is unique to a subset of MN. Confirmation of the novel antigen is then provided by immunohistochemistry and/or immunofluorescence studies that show granular subepithelial staining of the novel antigen along the capillary walls, followed by confocal immunofluorescence studies that show co-localization of the novel antigen with IgG along the capillary walls, ideally elution of IgG from frozen biopsy material to show that the deposited IgG is specific for the novel antigen and, finally, serum western blot analysis to show that circulating antibodies to the novel antigen are present in the serum.

Six candidate antigens have been discovered using these techniques in the past few years (Table 1). Putative antigens EXT1 and EXT2 were discovered in 2019, NELL1 and SEMA3B in 2020, and PCDH7, HTRA1 and NCAM1 in 2021. EXT1 and EXT2 were the first novel proteins found in a subset of patients with MN. Granular EXT1 and EXT2 deposits were detected in MN secondary to autoimmune disease, mostly lupus65. Patients with MN associated with EXT1 and EXT2 deposits were young, predominantly female and their kidney biopsy samples showed features of MN usually associated with an autoimmune disease such as a full-house pattern of immunoglobulin on immunofluorescence studies, tubuloreticular inclusions in the endothelial cells and mesangial deposits. However, antibodies to EXT1 and EXT2 have yet to be found and these proteins are considered putative antigens. Positive staining for EXT1 and/or EXT2 is found in 30–40% of pure lupus MN (LMN; also referred to class V lupus nephropathy) and in around the same percentage of mixed class lupus nephropathy, that is, class III or class IV associated with class V. Patients with LMN and positive staining for EXT1 or EXT2 have fewer chronicity features, including glomerulosclerosis, tubular atrophy and interstitial fibrosis, and also have a better prognosis than those who are negative for EXT1 and EXT2 (refs66,67).

NELL1 seems to be the second most common antigen following PLA2R. It is present in most patients with MN and no underlying disease association (pMN) but is also present in some patients with malignancy (sMN)68,69. One of the unique features of kidney biopsy samples is that staining for NELL1 can be segmental in some of the glomeruli69,70.

SEMA3B is another unique antigen in that it is primarily present in children (<2 years of age) and young adults. In children, kidney biopsy samples also show IgG staining along the tubular basement membrane. Interestingly, the tubular basement membrane deposits are negative for SEMA3B71. NCAM1 was identified as an antigen in both pMN and LMN72. Patients with NCAM1-associated LMN were younger, predominantly female and had a history of lupus, all of which are distinct features from those seen in the usual patients with MN. Similar to LMN associated with EXT1 and EXT2, NCAM1-associated LMN is not restricted to pure class V LMN but is also present in some patients with LMN who also have proliferative lupus nephritis.

PCDH7-associated MN is present in patients with a mean age of 63 years, close to that of the most common form of MN73. Most patients seem to not have an associated underlying disease but ~20% of patients with PCDH7-associated MN have a history of malignancy. Kidney biopsy samples lack complement deposits on immunofluorescence study. In addition, non-nephrotic-range proteinuria (proteinuria <3 g/day) is observed and remission follows conservative management in some patients with PCDH7-associated MN.

HTRA1-associated MN is present in patients with a mean age of 67 years and characterized by an IgG4-dominant subclass in the immune deposits without association to another disease except for anti-neutrophil cytoplasmic antibody-associated vasculitis in 1 of 14 patients74. Sera from two patients reacted by immunoblotting with glomerular extracts and with recombinant human HTRA1 under reducing and non-reducing conditions. Longitudinal sampling in these two patients suggests that HTRA1 antibody levels are correlated with clinical activity.

Whether these new antigens are true antigens or biomarkers is controversial as they have only been characterized in the past few years. As described, each antigen-associated MN has its own specific features, including demographic characteristics, immunopathological and sometimes morphological features, and associated diseases. The minimal definition of an antigen is the presence of the relevant antibodies in the blood and, ideally, in biopsy samples. Although co-localization of antigen and antibody by confocal microscopy is suggestive, definitive evidence of the reactivity of the deposited antibody against the potential antigen requires elution experiments that are hampered by the small size of the tissue specimen. Among the new potential antigens, such demonstration has only been achieved for PCDH7 (ref.73). Further evidence of the pathogenic effect of the antibodies can be provided by correlation of antibody levels with clinical course, early recurrence in the transplanted kidney and development of experimental models. A few cases showing the parallel outcomes of immunological and clinical activity have been reported69,71,73,74. No observation of early recurrence after transplantation has been reported and animal models are not yet available.

Of note, more than a decade after the discovery of PLA2R, the only experimental model of PLA2R-associated MN is with the mouse antigen75 and evidence of pathogenicity in humans mostly relies on early recurrence after transplantation76,77 and time-course measurement of PLA2R antibody levels that precedes proteinuria78,79. Yet, the discovery of the role of the PLA2R antibody in MN has induced a paradigm shift in patient care, showing the way for future well-conducted clinical studies that aim to define the diagnostic and predictive values of potential antigens involved in MN. The pathophysiology of these new antigens is essentially unknown and will require further studies.

Exogenous antigens

Exogenous proteins, whether they are present or not in humans, can induce the production of allo-antibodies or xeno-antibodies, respectively. Important features of these proteins are their specific physicochemical properties that may lead to their trapping in the GBM. The first observation implicating a food antigen was reported in children with cationic bovine serum albumin (BSA)-related MN80. This observation was also inspired by an experimental model81,82. Some patients, mostly infants, with MN had high serum titres of anti-BSA antibodies reacting with one peptide region of BSA but not with human serum albumin. Only infants had circulating cationic BSA, which could interact with the negatively charged glomerular capillary wall. Why cationic BSA was formed is not known but differences in food processing or in the intestinal microbiota might be responsible for BSA modifications.

Other food antigens or non-dietary antigens from the environment might also be involved in MN. Extremely rare forms of allo-immune MN have been described in children affected with rare lysosomal storage diseases (mucopolysaccharidosis type VI and Pompe disease) receiving enzyme replacement therapy83,84. Because of the absence of enzymes, therapeutic proteins are potential allo-antigens that trigger immunization.

Autoimmune reactions

Regardless of the target antigen, the common denominator in MN is the accumulation of discrete deposits containing immunoglobulin and antigen that form and expand beneath the basal surface of the podocyte (Fig. 2). The mechanisms underlying the loss of tolerance to these self-antigens are not well understood but likely involve genetic factors, heightened expression of target antigens owing to polymorphisms in regulatory elements, upregulation by environmental factors, or even pathologic and dysregulated production of the antigen as might occur in malignancy. It is also not known why some patients have circulating antibodies well before the onset of nephrotic syndrome and even proteinuria85.

Fig. 2: Pathomechanisms of injury in PLA2R-associated membranous nephropathy.

a | At the initiation of the humoral autoimmune response, the podocyte expresses phospholipase A2 receptor (PLA2R) and complement inhibitors such as complement receptor 1 (CR1) at the cell surface and has a cytoskeleton reflective of the differentiated podocyte state, with interdigitating foot processes bridged by slit diaphragms. Circulating auto-antibodies begin to target PLA2R on the basal aspect of the podocyte. Ongoing synthesis and delivery of PLA2R to the cell surface enables continued deposit formation and growth in the presence of circulating auto-antibodies. b | Immune deposits (stage 1) containing antigen and immunoglobulin form beneath the podocyte, where they begin to activate complement. The terminal complement components C5b–9 (membrane attack complex (MAC)) insert into the podocyte membrane and enable calcium influx, which initiates several maladaptive pathways. C3a and C5a generated by the complement cascade bind to and activate their cognate receptors C3aR1 and C5aR1, stimulating pathways that lead to the degradation of cytoskeletal elements. CR1 is downregulated, which enables complement-mediated cytotoxicity. The result is the simplification of the podocyte cyto-architecture, loss of slit diaphragms and increased flux of protein into the urinary space. PLA2R continues to be produced by the podocyte, leading to an increased mass of the immune deposits and ongoing complement activation. c | With ongoing injury, the podocyte secretes additional extracellular matrix components between (stage 2) and around (stage 3) the immune deposits, leading to the increased overall thickness of the glomerular basement membrane.

Several studies suggest an overall dysregulated immune phenotype in MN86,87 characterized by a decreased proportion of regulatory T cells among all lymphocyte subpopulations in untreated patients with MN88. Numbers of plasma cells and regulatory B cells were statistically higher in patients with MN compared with healthy individuals or individuals with non-immune kidney disease and the amount of in vitro-expanded PLA2R-specific memory B cells could be correlated with circulating PLA2R antibody titres89. The specific site at which the immune response to PLA2R is initiated remains speculative90 but intrarenal B cells in tertiary lymphoid follicles have been noted91,92. These tertiary follicles could represent the propagation of the immune response triggered by PLA2R shed from podocytes as exosomes into the tubular lumen93 and later captured by intrarenal dendritic cells. The observation that the risk of recurrence after kidney transplantation is dependent on the donor’s gene variants of HLA-D and PLA2R1 can be seen as further evidence of a kidney-based source of antigen exposure90.

The paradigm of podocyte injury induced by the subepithelial immune deposits was elucidated in the experimental rat model of Heymann nephritis94. In this model, activation of the complement system and assembly of the terminal complement components C5b–9 were both necessary to induce podocyte injury and proteinuria. In the absence of complement-activating IgG or factors such as complement component C6, subepithelial deposits would form but no further injury would occur. Evidence for complement activation in human MN has been circumstantial and based on the consistent presence of specific complement factors within the subepithelial deposits. In routine immunofluorescence staining, IgG and C3 are present but C1q is usually weak or absent, suggesting that the classical complement pathway activation has a minor role in established disease. However, the fact that early deposits contain more IgG1 and IgG3 whereas later-stage deposits are enriched in IgG4 suggests that the classical complement pathway might initiate disease, which is then propagated by the alternative pathway or the lectin pathway95. The consistent presence of C4 (ref.96) and of mannan-binding lectin (MBL) in many97 but not all98 patients with MN implicates the lectin pathway, but many components of the alternative pathway are also detected when assayed by mass spectrometric techniques99. The common final pathway is thought to involve the insertion of C5b–9 (also known as the MAC) channels into the podocyte membrane. This breach of cell integrity causes sublethal cell injury and the activation of maladaptive pathways causing cytoskeletal disassembly, loss of slit diaphragms and, over time, the production of normal and ectopic basement membrane elements100.

Mouse models using passive transfer of human or rabbit antibodies to PLA2R75 or THSD7A101,102 have been developed but they have not yet convincingly established a definite role for complement. Sophisticated co-culture models, such as the glomerulus-on-a-chip, hold promise for investigating the harmful effects of human anti-podocyte antibodies103. In a culture model of PLA2R-expressing podocytes, PLA2R IgG4 antibodies, especially those bearing glycan chains that lack terminal galactose residues, stimulated the lectin pathway through MBL and MBL-associated serine proteases to cause podocyte injury104. A novel finding from this work is the upregulation of receptors for C3a and C5a on the podocyte, also observed in human MN biopsy specimens, that may augment the cytotoxicity instigated by C5b–9 through cytoskeletal degradation in response to the anaphylatoxins generated by subepithelial activation of complement.

Research continues into non-complement-dependent mechanisms, for example, direct interference in normal pathways by the auto-antibodies. THSD7A antibodies seem likely to have direct effects on the slit diaphragm structure and function102,103 given the close association of THSD7A with this structure. Intermolecular epitope spreading to intracellular antigens105 or complement regulatory factors106 may also augment the injury process.

Nephropathy

The downstream effects of injury caused by the subepithelial deposits are enormous, starting with the failure of the glomerular filtration barrier owing to the complement-mediated podocyte injury and the spilling of massive amounts of protein into more distal nephron segments. One consequence of delivery of these large amounts of protein, including specific proteases, to the distal nephron is the activation of the epithelial sodium channel ENaC, which is responsible for sodium reabsorption in the collecting duct, causing volume overload, weight gain, and localized oedema or generalized anasarca. The imbalance of promoters and inhibitors of the coagulation system in the setting of increased urinary losses and hepatic synthesis favours the thrombophilic state, which is more pronounced in MN than in other nephrotic disorders for as yet unknown reasons107,108. Deep vein thromboses, renal vein thrombosis and pulmonary embolism are all potential consequences of the nephrotic state in MN and are associated with the severity of hypoalbuminaemia108,109. Other consequences of the nephrotic state include mixed hyperlipidaemia, vitamin D deficiency and a general state of immunosuppression due to urinary loss of innate and humoral immune effectors such as complement factors and immunoglobulins. Similar to other glomerular diseases with sustained proteinuria over months to years, renal function can decline with progressive tubular atrophy and interstitial fibrosis33. Patients who develop end-stage MN and receive a kidney transplant are at risk of recurrence of the disease in the allograft if the circulating antibodies are still present or recur after transplantation.

Diagnosis, screening and prevention

Adults

Clinical presentation

Nephrotic syndrome, defined as proteinuria >3.5 g per day and serum albumin <3.5 g/dl (when measured by bromocresol green) or <3.0 g/dl (when measured by bromocresol purple or immunonephelometric methods), respectively, is present in around two-thirds of patients with MN at presentation and can be severe1,110. The other third of patients present with asymptomatic proteinuria, usually ≤3.5 g per day. In most patients, GFR is normal and urinary sediment is unremarkable, although microscopic haematuria may be present in <25% of patients. Hypertension at presentation is uncommon (<20% of patients), which explains why most patients do not tolerate high-dose angiotensin II blockade. Thromboembolic events are reported in up to 8% of patients, with renal vein thrombosis accounting for 30% (Box 1). Hyperlipidaemia is common and characterized by an increase in total and LDL cholesterol and a decrease in HDLs, which is associated with a markedly increased risk of both myocardial infarction and coronary death compared with that of healthy individuals as well as with an increased risk for thromboembolism111. Rare cases of crescentic MN, usually presenting with proteinuria >3.5 g per day, haematuria and reduced GFR, in the absence of anti-neutrophil cytoplasmic antibodies or GBM antibodies, have been reported112.

Box 1 Complications of membranous nephropathy and its treatments

Nephrotic syndrome

Tiredness, oedema, dyspnoea, nausea, anorexia, ascites, venous thrombosis, arterial thrombosis, infections, kidney failure.

Diuretics

Hypokalaemia, hyponatraemia, hypomagnesaemia, alkalosis, gout, ototoxicity (with high-dose furosemide), muscle aches.

Prednisolone

Cushing face, obesity, skin bruising and striae, diabetes, osteoporosis, cataracts, infections, wound healing.

Cyclophosphamide

Anaemia, leukocytopenia, thrombocytopenia, infections, nausea, anorexia, bladder mucosal irritation with haematuria, liver function abnormalities, hair loss, infertility, malignancy, myelodysplasia.

Calcineurin inhibitor

Nephrotoxicity, diabetes, hair growth, gingiva hyperplasia, hypertension, liver dysfunction, neurotoxicity.

Rituximab

Infusion reaction, infections, hypogammaglobulinaemia, antibody formation.

See also Supplementary Table 1.

Histopathology

Kidney biopsy is the standard diagnostic approach for MN. On light microscopy, early stages of MN may show normal-appearing GBMs113. At later stages, basement membrane spikes and pinholes can be seen on silver methenamine and periodic acid-Schiff stains (Fig. 3).

Fig. 3: Kidney biopsy findings of membranous nephropathy properties of the glomerulus in membranous nephropathy.

 

a | Light microscopy image showing thickened glomerular basement membranes (arrows; periodic acid-Schiff stain, 40×). b | Immunofluorescence microscopy image showing granular staining for IgG along the capillary walls (40×). c | Electron microscopy image showing subepithelial electron-dense deposits (black arrows) and basement membrane material between the electron-dense deposits (white arrows; 4,800×). d | Immunofluorescence microscopy image showing staining for phospholipase A2 receptor (PLA2R) along the capillary walls (40×).

Full size image

Proliferative features, such as mesangial and endocapillary proliferation, are typically absent113. In very rare cases, a concurrent crescentic pattern of injury is observed. In immunofluorescence microscopy, diffuse and granular staining for IgG, C3, and κ and λ light chains is seen along the capillary walls in pMN. In electron microscopy, numerous electron-dense deposits are seen in the basement membrane beneath the podocytes that show extensive foot process effacement even at the early stages. These subepithelial deposits are separated by expansions of basement membrane material or covered with extracellular matrix at later stages114.

Four stages are defined according to the location of the subepithelial deposits and matrix accumulation: stage 1, sparse small deposits without thickening of the GBM; stage 2, more extensive subepithelial deposits with the formation of basement membrane spikes between the deposits and thickening of the GBM; stage 3, a combination of stage 2 with deposits completely surrounded by basement membrane (intramembranous deposits); and stage 4, incorporation of deposits in the GBM, which are irregularly thickened (burned-out disease). In stage 4, the deposits are often fading, becoming less electron dense.

Features suggestive of sMN include mesangial or endocapillary proliferation; a full-house pattern of immunoglobulin staining, including staining for IgA and C1q on immunofluorescence microscopy; mesangial and/or subendothelial electron-dense deposits or deposits along the tubular basement membrane and vessel walls; substructures in the deposits; and endothelial tubuloreticular inclusions on electron microscopy115. The presence of scant superficially scattered subepithelial deposits on electron microscopy suggests drug-associated or malignancy-associated sMN. Staining for IgG subclasses may help in differentiating pMN from sMN. IgG1, IgG2 and IgG3 predominate in class V lupus nephritis, whereas IgG4 is the prevailing subclass associated with variable amounts of IgG1 in PLA2R-associated and THSD7A-associated pMN69,71,116. The prevailing subclass in MN associated with newly characterized antigens is IgG1 (ref.117). In early reports in malignancy-associated sMN, IgG4 staining was usually absent118. However, one study found no differences in the IgG subclass distribution between patients with pMN and those with malignancy-associated sMN119. Furthermore, levels of antigen-specific IgG4 antibodies were not different between primary and malignancy-associated sMN and levels of all IgG subclasses did not differ between these groups.

Staining of kidney biopsy samples for PLA2R can also diagnose PLA2R-associated MN in patients who have negative PLA2R antibody serology80. This might occur if serum samples are collected when the patient is in immunological remission either spontaneously or following immunosuppressive therapy or PLA2R antibody serology may be falsely negative early in the disease course owing to the phenomenon of the kidney behaving like a ‘sink’120. In this scenario, circulating PLA2R antibodies bind to the target antigens on the podocyte and are rapidly cleared from the blood. Only when the antibody production rate exceeds the buffering capacity of the kidney will seropositivity become apparent. Hence, serial assessment of PLA2R antibody levels should be performed in patients with positive glomerular PLA2R staining who are initially seronegative but have persistent proteinuria12. By contrast, positive PLA2R antibody serology and negative glomerular PLA2R staining are uncommon121,122 and very likely reflect differences in staining techniques123.

Indications for kidney biopsy

Kidney biopsy is costly and can result in major complications123,124,125,126,127. Given the high specificity of PLA2R antibodies in patients with MN and the fact that PLA2R antibodies have not been detected in other glomerular diseases or healthy individuals, deferral of a kidney biopsy has been suggested in patients who have nephrotic syndrome and PLA2R antibodies12,19. This proposal has been supported by a study that showed that, in patients with preserved kidney function (eGFR >60 ml/min/1.73 m2), no evidence of secondary cause (Box 2) and no diabetes mellitus, a positive serum PLA2R antibody titre equals a 100% probability of diagnosing MN and is therefore a reliable non-invasive method for the diagnosis of pMN128. In these patients, kidney biopsy did not provide any valuable information that altered treatment. This non-invasive diagnostic approach might be especially important for those at high risk of complications or in whom a kidney biopsy is contraindicated129. However, if kidney function is impaired or the patient has evidence of a potential secondary cause for MN, including diabetes mellitus, a kidney biopsy is needed to exclude concomitant kidney disease (for example, underlying diabetic nephropathy, acute interstitial nephritis or crescentic glomerulonephritis) and to estimate the extent of interstitial fibrosis and tubular atrophy, which may add useful information to guide management. Box 2 provides guidelines for the evaluation of associated conditions in patients with MN regardless of serology. The non-invasive diagnostic approach is supported by the new Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on the management of glomerular disease130. In patients with a PLA2R− biopsy sample, staining for THSD7A, EXT1, EXT2, NELL1, NCAM1, SEMA3B, PCDH7 and HTRA1 antibodies should be performed depending on age, immunofluorescence pattern (segmental) and associated condition (autoimmunity).

Box 2 Evaluation for associated conditions (regardless of serology)

Laboratory

• Phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A) antibody testing
• Complete blood count
• Extensive laboratory analysis with serum albumin
• Urinalysis
• 24-hour urine collection for protein quantificationa and creatinine clearance
• Antinuclear antibodies and anti-double-stranded DNA antibodies
• Hepatitis B and C virus serology
• Serum C3 and C4 complement levels
• Monoclonal protein studies, including serum-free light chains and serum protein immunofixation

Age-appropriate cancer screening

Sarcoidosis

Autoimmune thyroiditis

Drug exposure

• NSAIDs, penicillamine, elemental mercury, antitumour necrosis factor agents

Bone marrow transplant and graft-versus-host disease

IgG4-related disease

• In patients with pancreatitis, tubulointerstitial nephritis or sialadenitis

Rare infectious causes

• Schistosomiasis, malaria (specifically quartan fever), and congenital and secondary syphilis

The initial work-up for associated conditions may vary depending on local clinical practice. aA reasonable compromise is to collect an ‘intended’ 24-hour urine sample and measure a urinary protein to creatinine ratio in an aliquot of the collection.

pMN, sMN and a new antigen-based classification

In ~80% of patients, MN appears without an underlying cause and presents as a kidney-specific autoimmune disease. The target antigen in ~70% of patients is PLA2R, followed, in decreasing percentages, by NELL1, PCDH7, THSD7A, HTRA1 and SEMA3B (mainly in children and young adults), NCAM1, and unknown in the remaining 10–15% of patients with pMN. In ~20% of patients, MN occurs in association with other clinical conditions and is categorized as sMN5. Patients with pMN and those with sMN have similar clinical renal presentations.

However, this dichotomization of MN into primary and secondary has been challenged5,131. The complexity arises from the fact that clinical findings of the presence of antibodies do not accurately align with the definitions of pMN and sMN. Some patients with apparently sMN are also positive for PLA2R antibodies, most commonly those with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or sarcoidosis132,133,134,135. Whether these patients have true sMN or coincidental PLA2R-associated MN with a secondary disease is unclear. The facts that patients may enter spontaneous remission without treatment of the secondary cause or that treatment of the secondary cause does not result in remission of MN support the view that these antibodies occur coincidentally136. The same is true for patients with THSD7A-associated MN, for which an association with malignancy exists64,137. In these patients, remission has been observed with treatment of the malignancy alone63,64,137,138, but most patients with THSD7A-associated MN, with or without concomitant malignancy, respond to immunosuppression therapy139,140. In addition, most patients with NELL1-associated MN present without evidence of concomitant disease, but a concomitant malignancy is present in some of these patients68,69,137. Thus, a new molecular classification for MN based on target antigen has been proposed5,131. Future studies should enable the proposition of a better disease classification based on the presence of antibodies and the antigen specificity as well as the proven association (or not) with an underlying cause.

PLA2R antibody assays and identification of other target antigens

Various assays are available to detect PLA2R antibodies. The most commonly used assay is the ELISA commercialized by Euroimmun, which is 99.6% specific and enables the quantification of PLA2R antibody levels. The indirect immunofluorescence assay (IFA) from the same provider is a bit more sensitive than the ELISA and is 100% specific but does not enable quantitative assessment141. The currently recommended reference ranges for the ELISA assay are <14 relative units (RU)/ml (negative), 14–20 RU/ml (borderline) and >20 RU/ml (positive). Improved sensitivity without affecting specificity has been suggested by reducing the cut-off from 20 RU/ml to 2 RU/ml (refs142,143) or by using a combination of IFA and ELISA128. In this study, all patients with ELISA values >2 RU/ml and <20 RU/ml and a positive IFA had MN confirmed on biopsy. An addressable laser bead immunoassay, showing similar performance to the IFA assay, has been developed but is not clinically available144. ELISA and IFA remain less sensitive than western blot analysis (not used in clinical practice) and antigen staining of the kidney biopsy sample121,145. Thus, these techniques may fail to detect PLA2R antibodies in patients with proven PLA2R-associated MN.

An indirect immunofluorescence assay for THSD7A antibodies is commercially available (Euroimmun) but tests for NELL1, NCAM1, SEMA3B, PCDH7 and HTRA1 antibodies have not yet been developed. However, antibodies specific for the antigens are commercially available and can be used for the detection of antigen after retrieval in paraffin-embedded kidney biopsy samples117.

MN and malignancies

The prevalence of malignancy in patients with MN is estimated at 6–22%, most commonly occurring in patients >60 years of age with most cancers discovered before or at the time of the diagnosis of MN146; whether these are coincidental events or represent an aetiological association is unclear. Three criteria to ascertain an aetiological association have been proposed: remission occurs after complete removal of the tumour, renal relapse accompanies recurrence of the neoplasia, and the detection of tumour antigens and antitumor antibodies within subepithelial immune deposits147. However, clinical application of this paradigm can be difficult, in part because culprit antigens are generally unknown. Although fulfilment of these criteria provides strong support for an aetiological link, especially in patients with THSD7A-associated MN, their absence does not refute it.

The role of malignancy in patients with MN who are PLA2R antibody positive is debatable148. PLA2R antibody positivity has been reported in a minority of patients with MN associated with solid tumours but, in one study, no patient with PLA2R-associated MN went into remission with malignancy treatment alone, suggesting a coincidental process rather than a causal relation131. However, 10% of the patients tested negative for all seven known antigens associated with MN and 25% of these had a malignancy131. In a large series of 91 patients with NELL1-associated MN, 33% had an associated malignancy68. Patients with NELL1-associated MN were older than patients with PLA2R-associated MN (mean age 66.8 ± 10.8 years versus 56.4 ± 13.9 years, respectively) and patients with NELL1-associated MN with malignancy were significantly older than patients with NELL1-associated MN without malignancy (71.0 ± 8.6 years versus 65.0 ± 10.5 years; P = 0.01). By contrast, in a study from China that included 15 patients with NELL1-associated MN (median age 49 years, range 44–50 years), no association with malignancy was found149.

In practice, we recommend that patients who present with MN should undergo a thorough evaluation for possible occult malignancy, especially if they are negative for PLA2R antibodies or positive for THSD7A or NELL1 antibodies. The evaluation should consist of most age-appropriate screening tests, including colon cancer screening, mammography, kidney ultrasonography, a prostate-specific antigen assay in men and a chest radiograph (or a chest CT in patients at high risk) (Box 2; Supplementary Box 1)134. Ongoing vigilance is necessary because the diagnosis of cancer may not be immediately obvious.

Children

MN rarely affects children (0.1 cases per 100,000 per year)150. However, its frequency may be underestimated in this age group as children <10–12 years of age with nephrotic-range proteinuria are usually treated empirically with oral glucocorticoids without performing a renal biopsy. As childhood progresses, MN as a cause of nephrotic syndrome becomes more frequent, increasing from 1–2% at ages 1–5 years to 18–22% at ages 18–20 years. A rare form of congenital MN that is limited to only a few families worldwide is caused by a maternal homozygous mutation in MME, which encodes NEP52,151. The SEM3B-associated form of pMN typically occurs in children (even <2 years of age) and in young adults70. BSA-related MN should also be considered in children <5 years of age80.

Similar to adults, particularly in regions with endemic HBV infection, young children presented with HBV-associated MN that is responsive to anti-viral treatment152. This form of MN has decreased steeply with widespread vaccination against HBV152. In adolescents, MN can occur in patients, typically female, with renal involvement secondary to SLE (class V lupus nephritis). At this age, pMN also occurs, especially but not exclusively associated with PLA2R153.

When MN is diagnosed in a child, the most likely causes must be identified, taking into account the child’s age153. Briefly, the congenital NEP form of MN must be suspected in neonates; the BSA-related form in infants; the SEMA3B form in children aged 1–3 years; the enzyme replacement therapy form in children with a metabolic disease receiving recombinant human arylsulfatase B or α-glucosidase;154 the HBV-associated form in children living in areas with endemic HBV infection, particularly in those aged 5–7 years; and either SLE or primary forms of MN driven by one of the known antigens, particularly PLA2R, in children aged >10–12 years. In addition to SEMA3B-associated MN, the actual incidence of MN involving other known antigens in children still needs to be investigated; forms of MN associated with THSD7A have been described as well as a single patient each with NCAM1-associated and with EXT1 and EXT2-associated forms of MN.

The outcome of pMN in children is unpredictable and spontaneous remission occurs in ~30% of patients. Overall, prognosis in paediatric forms of MN seems better than in adults153. In a retrospective study of 217 children with pMN, after a median follow-up of 45 (23.5–74.0) months, the cumulative kidney survival rates at 5 years and 10 years after renal biopsy were 95.3% and 67.8%, respectively155.

Low-income regions

In low-income settings, patients with nephrotic syndrome due to MN often present with late-stage disease, sometimes with complications156. The presence of vascular thrombosis might prevent a kidney biopsy as patients need immediate therapeutic anticoagulation. Lack of specialist facilities limits the ability to fully evaluate these patients, including investigations to rule out secondary causes of MN, serological testing and kidney biopsy. Special attention needs to be given to rule out locally prevalent infections such as HBV or HCV. According to the Global Kidney Health Atlas, laboratory facilities for assessment of urinary protein levels or albumin creatinine ratios were available in <5% and <55% and renal pathology services were available in only 12% and 46% of low-income and lower-middle-income regions, respectively157. Even where pathology is available, immunofluorescence microscopy, PLA2R staining or electron microscopy are not routinely performed in many centres.

Prevention

Infections with HBV, HCV or HIV are important preventable causes of MN. Of these, HBV infection can be prevented with a vaccine. According to the WHO, the prevalence of HBV infection is above the global median of 3.5% in sub-Saharan Africa, Southeast Asia, and Central Asia and exceeds 10% in several African regions. Universal HBV vaccination has effectively eliminated HBV-associated MN in high-income regions25. However, vaccination coverage remains dismal in low-income regions, with only 6% coverage in the WHO African region158.

Ingestion of heavy metals is associated with the development of MN. Heavy metals are often identified as contaminants in indigenous medications in India and China159. Better regulation of their use can help prevent MN. A study from China18 identified a strong association between air pollution and the increasing prevalence of MN. These data identify important gaps in our knowledge of the broader environmental determinants of this condition. The findings highlight the need to develop sustainable approaches to address the preventable causes of MN through actions that regulate the use of indigenous medicines and address emerging environmental challenges160.

Management

The initial non-immunosuppressive treatment of patients with pMN is guided by the complaints and (expected) complications at presentation and depends on the severity of proteinuria. Intensive monitoring enables the estimation of whether the patient is at risk of progressive kidney function deterioration. Immunosuppressive therapy, targeting the abnormal autoimmune response, should be considered in patients at risk. The introduction of a quantitative ELISA assay to measure antibody levels (only available for PLA2R antibodies) has enabled improved risk prediction and treatment guidance. For the time being, treatment approaches overall do not differ for the pMN forms associated with different antigens but most data are available for PLA2R-associated MN, which can facilitate more tailored management in patients with this form of MN. In patients with sMN, treatment of the underlying cause is warranted; however, patients with sMN who do not respond should receive therapy as proposed for pMN.

Supportive treatment of nephrotic syndrome

In nephrotic syndrome, oedema formation is dependent on water and sodium retention. Oedema contributes to immobility, fatigue, discomfort, skin blistering, infections and anxiety. Treatment is empirical and not evidence based161. Initial treatment includes a sodium-restricted diet and loop diuretics (furosemide or bumetanide). In patients with insufficient response, a second diuretic is added (thiazide, acetazolamide or a potassium-sparing diuretic). Theoretically, amiloride should be most advantageous in view of the evidence of increased activation of collecting duct ENaC162. In clinical practice, combinations of diuretics are often effective and the choice is guided by serum electrolyte levels and adverse effects of medications (Box 1). Patients with severe oedema often require hospital admission for treatment with intravenous diuretics, sometimes supplemented with albumin infusions161. In patients with hyponatraemia, water restriction is advised. After attaining sodium balance, blood pressure treatment should continue, targeting a blood pressure of 125–130/75–80 mmHg (refs130,163). Angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers are preferred as they have antiproteinuric effects and evidence suggests that their use may increase spontaneous remission rates in patients with pMN164.

Patients with nephrotic syndrome often develop hypercholesterolaemia. Guidelines advise the use of statin therapy in patients with persistent proteinuria and hypercholesterolaemia, especially in patients >50 years of age, to provide cardiovascular protection130. The use of statins in MN is further supported by their suggested role in the prevention of venous thromboembolic events165.

Indeed, patients with MN are at high risk of venous and arterial thrombotic events and the incidence is highest within 6–12 months after disease onset165. Thus, already at the time of presentation and diagnosis, prophylactic anticoagulation must be considered, taking into account individual patient characteristics, disease severity, and patient and family history (Supplementary Box 2). Most guidelines suggest the use of early, prophylactic anticoagulation according to algorithms that consider all parameters that affect the risk of thrombotic events and bleeding130. Treatment with warfarin is often used as standard therapy; however, there are good arguments to start treatment with low-molecular-weight heparin (at low to moderate dose intensity) at the time of diagnosis and switch to warfarin after 3 months if nephrotic syndrome persists166. In patients who are not candidates for warfarin or are treated with low-intensity low-molecular-weight heparin and have other risk factors for atherosclerotic vascular events, the use of aspirin must be considered167. The use of the new class of direct-acting oral anticoagulant drugs for thrombosis prophylaxis in nephrotic syndrome cannot be recommended168. Direct-acting oral anticoagulant drugs have not been studied in nephrotic syndrome and some patients with nephrotic syndrome developed thrombosis while using them169. High protein binding, the contribution of renal clearance to drug elimination, and the role of CYP3A4 and p-glycoprotein in drug metabolism (interfering with the kinetics of CNIs) could all affect their use in nephrotic syndrome168.

Immunosuppressive therapy

Cyclophosphamide and corticosteroids

Long before the identification of pathogenic antigens and specific auto-antibodies, pMN was recognized as an immune-mediated kidney disease, which fostered the use of prednisolone and other immunosuppressive drugs. RCTs showed that a combination of an alkylating agent (preferably cyclophosphamide) and prednisolone attenuated the progression to kidney failure in patients with MN170. However, the 2012 KDIGO guidelines did not recommend the unrestricted use of this therapy in patients with MN163. First, ~40% of untreated patients do not progress to kidney failure and many develop spontaneous proteinuria remission. Second, treatment with cyclophosphamide and corticosteroids is associated with considerable adverse effects (Box 1). Thus, it was advocated to restrict cyclophosphamide-based therapy to patients with MN and a high risk of kidney failure171. The guideline used persistent proteinuria of >4 g per day after 6 months of non-immunosuppressive therapy as the criterion of high risk. This criterion is not very accurate as the rate of spontaneous remission in these patients can be 45%8. The optimization of therapy (in terms of risk–efficacy balance) in patients with MN requires the early and accurate identification of patients who will progress to kidney failure (or will develop severe complications of nephrotic syndrome) and the introduction of effective, less toxic and alternative immunosuppressive therapies.

Risk prediction

Serum creatinine levels and proteinuria are the oldest biomarkers to estimate the risk of progressive disease associated with increased cardiovascular morbidity and mortality, and ultimately leading to kidney failure. Many other reported biomarkers lack sensitivity and/or specificity and have not been validated172 (Table 2). Baseline serum creatinine levels (cut-off value 1.5 mg/dl) identify patients at high risk relatively late at a time when kidney function is already compromised. While patients with persistent non-nephrotic proteinuria do not develop renal insufficiency173,174, nephrotic syndrome by itself is not an accurate prognostic biomarker as 40–45% of patients with nephrotic syndrome do not progress. One study showed that no less than 22% of patients with baseline proteinuria >12 g/day develop spontaneous remission164. Monitoring the course of kidney function and proteinuria during follow-up improves risk prediction164,175,176. The Toronto risk score combines kidney function and proteinuria parameters. This score has been validated and showed good performance177 but it can only be calculated after 12–24 months of follow-up. Measurement of low-molecular-weight proteins in urine at baseline provided similar accuracy as the Toronto risk score178. PLA2R antibody levels had no added value in a prognostic model that included proteinuria and serum creatinine levels but, in univariate analysis, high PLA2R antibody levels were specific (>80%) for predicting progression, with positive predictive values of 77% for 150–300 RU/ml and 87% for >300 RU/ml (ref.179).

Table 2 Clinical criteria for assessing the risk of progressive loss of kidney function

On the basis of biomarker assessment, the KDIGO 2021 guideline defines four risk categories: low, moderate, high and very high risk130 (Table 3). Although the disease characteristics of most patients may not perfectly fit one category and risk classification is not very accurate and partly based on low-quality data, the classification provides guidance in patient management. Because patients are seen at various phases of the disease, some entering immunological remission while others having increasing immunological activity, one cannot rely on a snapshot measurement of PLA2R antibody levels and proteinuria to predict the risk of progression but rather on the trajectory of these variables180. Thus, risk evaluation is a dynamic process and it is important to re-evaluate risk prediction at 3 months and 6 months after diagnosis as the changes in PLA2R antibody levels and clinical parameters may affect treatment indications. For example, a severe nephrotic syndrome with persistently high PLA2R antibody levels at 3 months will prompt starting immunosuppressive treatment. Further studies are needed to define more specific biomarkers that would predict progression at baseline ideally from the urine via exosomes, although the varying time points of sampling in the natural history of the disease will probably make interpretation difficult.

Table 3 Risk classification of patients with membranous nephropathy

CNIs and CD20-targeted therapy

The introduction of novel immunosuppressive agents offered hope for effective, less toxic therapy in patients with pMN. CNIs, such as cyclosporine and tacrolimus, indirectly affect B cell function and were proven effective in preventing immunological rejection after kidney transplantation. In addition, experimental studies suggested that CNIs directly target the podocyte, thereby reducing proteinuria181. The development of CD20 antibody treatments, such as rituximab, enabled effective depletion of B cells and thus the selective targeting of antibody production.

Both CNIs and rituximab, alone or in combination, are considered less toxic than cyclophosphamide and prednisolone. A review of clinical trials concluded that CNIs increased the likelihood of partial and complete proteinuria remission compared with no treatment (72–75% versus 22%)170. Additionally, remission rates at 12-month follow-up were comparable and numerically higher than those of cyclophosphamide treatment (CNIs 71–89%; cyclophosphamide 65–77%); however, the disease relapses after withdrawal of CNIs in most patients. In one RCT, relapses within 12 months after remission occurred in 40% of patients treated with tacrolimus and in 7% of patients treated with cyclophosphamide182. The efficacy of rituximab was also studied in RCTs. In the GEMRITUX trial, after 23 months of follow-up, the remission rate was 66% in patients treated with rituximab (total dose 750 mg/m2) and 45% in those who received conservative treatment8. In the MENTOR trial, although rituximab (total dose 4 g) was non-inferior to cyclosporine in inducing remission at 12 months after treatment start, more patients who received rituximab maintained remission at 12 months after withdrawal of therapy (60% versus 20%)9. In the STARMEN trial, although sequential therapy with tacrolimus (for 6 months) and rituximab (single dose 375 mg/m2) was inferior in inducing remission than the combination of cyclophosphamide and prednisolone (84% versus 58% at 24 months), the single dose of rituximab prevented relapse after withdrawal of tacrolimus10. The most recent RI-CYCLO trial compared rituximab (total dose 2 g) with cyclical cyclophosphamide and corticosteroids11. This study was underpowered and included mostly patients at moderate risk with low anti-PLA2R antibody levels. Although the authors concluded that the study provided “no signal of more benefit or less harm associated with rituximab”, the per-protocol analysis showed a significantly lower complete remission rate at 12 months in patients treated with rituximab than patients treated with cyclophosphamide and corticosteroids (13% versus 34%; OR 0.28, 95% CI 0.08–0.95). Subgroup analysis suggested superiority of cyclophosphamide treatment in men and in patients with increased proteinuria and decreased serum albumin levels.

Thus, there is evidence that CNIs and rituximab (alone or in combination) induce remission of proteinuria, which should translate into improved renal outcomes, although this has not yet been proven. However, overall failure rates with these agents are 30–35%, raising controversies on the ideal dosage and best protocol. Some data suggest that cyclophosphamide is more effective in patients at high risk183. The guidelines argue against the use of CNIs or rituximab in patients with deteriorating or decreased GFR; however, other data with rituximab are encouraging184.

Individualized treatment

Risk biomarkers, clinical characteristics, adverse effects, and patient and physician preferences can all be used to individualize therapy in patients with MN (Fig. 4). Patients at low risk do not need immunosuppressive therapy130. Patients at moderate risk can receive rituximab or a CNI — the controversial use of CNI in this indication is to decrease the duration of proteinuria in those with a high potential of spontaneous remission. In patients at high risk, single-agent rituximab treatment is now established in addition to combinations of cyclophosphamide and prednisolone. However, the long-term benefit on kidney function of CD20 antibody therapy remains unclear and its efficacy to induce immunological remission seems to be reduced in patients with very high antibody titres183, although this view has been challenged185. Patients at very high risk should receive a combination of cyclophosphamide and prednisolone.

Fig. 4: Risk-based therapy in membranouse nephropathy.

In patients with primary membranous nephropathy (MN), efforts must be made to estimate the risk of kidney function deterioration using clinical criteria (Table 2) and risk classification (Table 3). As the risk profile will change during the follow-up period, risk should be evaluated regularly. Immunosuppressive therapy should not be used in patients at low risk. By contrast, patients at very high risk should receive the most effective but also most toxic therapy with cyclophosphamide and prednisolone. Different treatment options can be considered in patients at moderate and high risk, guided by patient and physician preference, expected adverse effects, therapy reimbursement, and other factors. Although calcineurin inhibitor (CNI) monotherapy is probably less effective, it is an option in patients at moderate risk of progression. CNIs shorten the period of proteinuria and can be used in a regimen combined with rituximab. Adapted from ref.130, KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases.

In the individual patient, the ultimate choice of treatment requires a discussion of benefits and risks considering the expected burden of adverse effects (Supplementary Box 3; Supplementary Tables). Future studies should define the best dosage and protocols adapted to the patient and integrate the new advances in the field of immunotherapy, including new CD20 antibodies, belimumab (a monoclonal antibody that inhibits the B cell-activating factor (BAFF)), anti-plasma cell therapy and anti-complement therapy. These new agents should be discussed in patients with refractory disease in expert centres.

Monitoring immunosuppressive therapy

Immunosuppressive therapy is usually given according to standard treatment protocols of therapy dosing and duration130. Patients should be monitored for adverse effects (Box 1) and therapy efficacy is ascertained by improvements in proteinuria, serum albumin levels and (if applicable) serum creatinine levels. Clinical response to cyclophosphamide or rituximab is notably slow and partial remission of proteinuria only develops after 6–18 months, often after withdrawal of therapy10,78. Thus, in patients with persistent nephrotic syndrome but stable eGFR after 6 months, no change in treatment is required.

In PLA2R-associated MN, measurement of PLA2R antibody levels aids treatment decisions (Fig. 5). Cyclophosphamide was more effective than rituximab in inducing immunological remission in patients with high PLA2R antibody levels186, which explains the low (30%) remission rate after one dose of rituximab in patients with high antibody levels79. Treatment should induce immunological remission. The disappearance of PLA2R antibodies (using the IFA; when using ELISA, the titre should fall below 2 RU/ml) predicted remission of proteinuria, whereas persistence of PLA2R antibodies after therapy was associated with progressive disease78,187.

Fig. 5: Adjustment of therapy using PLA2R antibody monitoring.

In patients with phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy, regular evaluation of the course of PLA2R antibody (PLA2R-Ab) levels after the start of immunosuppressive therapy enables the optimization of immunosuppressive therapy in the individual patient. Immunological remission is the goal of therapy. The disappearance of antibodies can be used to taper or withdraw therapy, whereas persistence or increasing antibody levels should lead to continuation of therapy or to switching to an alternative drug regimen. No validated cut-off values exist. A negative immunofluorescence assay result or PLA2R ELISA titre <2 RU/ml defines the absence of PLA2R-Ab. When measuring PLA2R-Ab at regular intervals (every 2–3 months), a large decrease of antibody levels (>50%) to values <50 RU/ml may be sufficient as an initial response criterion. CNI, calcineurin inhibitor; CP, cyclophosphamide; RTX, rituximab. Adapted from ref.130, KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases.

Full size image

Children

Given the rarity of paediatric MN, children with MN should be managed in expert centres and treatment should be targeted. Secondary forms of MN require management of the underlying condition (for example, HBV infection or SLE)188. Primary forms of MN, especially in adolescents, can be treated similarly to adults. Supportive therapy with inhibitors of the renin–angiotensin system and low-salt diet is essential. A key difference to the situation in adults is that many children, especially if <10–12 years old, are diagnosed with MN after already having received oral prednisolone for 4–8 weeks. Treatment with CNIs or rituximab follows the same dosing regimen employed for adults. When these therapies are available, cyclophosphamide is rarely used189.

Low-income regions

In resource-poor settings, patients often do not present until the disease has progressed to a severe nephrotic state and/or a complication has occurred, for example, vascular thrombosis or infection such as pneumonia. This prevents the timely initiation of non-immunosuppressive antiproteinuric therapies with drugs that block the renin–angiotensin system. The lack of specialist nephrologists limits the application of personalized medicine principles such as individualizing evidence-based therapies according to the patient’s risk status190. Finally, the full range of treatments may not be available because a drug (for example, rituximab) is not marketed in the country or is too expensive. New treatments that are currently under investigation and monitoring approaches, such as PLA2R antibody assays, are likely to further increase treatment costs and therapeutic inequity. Treatment compliance can be a problem and contribute to suboptimal responses.

Potential solutions include a resource-sensitive adaptation of clinical practice guidelines by global organizations such as KDIGO and ISN191, using information technology tools to support the implementation of standard treatment pathways through the available workforce via linking with expert centres by international cooperations (for example, through ISN Sister Centers programmes or Project ECHO), greater use of generic compounds and clinical trials of therapies to optimize the risk–benefit balance (for example, eliminating methylprednisolone pulses in the Ponticelli regimen). Advocacy is needed for greater involvement of low-resource regions in clinical trials of novel therapies with the commitment to make these treatments available as has been done for HIV therapeutics and SARS-CoV-2 vaccination.

Patients with a kidney allograft

Patients with pMN who do not tolerate or do not respond to immunosuppressive therapy will develop kidney failure and need kidney replacement therapy. Kidney transplantation is considered the best treatment option provided there are no contraindications for this surgical procedure. Apart from the routine pretransplant evaluation, in patients with pMN, the risk for recurrent disease after kidney transplantation should be assessed and discussed. In these patients, the histological recurrence rate is 50–60% and the clinical recurrence rate is 30–40%192,193,194,195,196,197. Increased age, short waiting time to receiving the transplant, heavy proteinuria at pretransplant evaluation, and corticosteroid-free maintenance immunosuppression after transplantation are associated with an increased risk of recurrence192,193,197,198. Recurrence rates are approximately threefold higher after transplantation of an organ from a living related donor195,196, compatible with the observation that the risk of recurrence is dependent on donor HLA-D and PLA2R1 variants90.

Pretransplant and post-transplant measurement of PLA2R antibody levels aids patient management (Supplementary Box 4). The most critical step is to unequivocally establish that MN is associated with PLA2R. In PLA2R-associated MN, the pretransplantation presence of PLA2R antibodies, especially at high titres, is associated with a high risk of recurrence, whereas undetectable PLA2R antibody levels predict a low risk195,197,199. A gradual decrease and disappearance of PLA2R antibodies after transplantation are associated with a reduced risk of recurrence (25% versus 71%)195. Although PLA2R antibody level measurement is therefore helpful, there are pitfalls and exceptions to the rule (Supplementary Box 4).

Rituximab treatment is effective in patients with recurrent MN following kidney transplantation193,197. Most patients (>80%) respond with complete or partial remission of proteinuria, which is preceded by the disappearance of the antibodies in patients who are PLA2R antibody positive. In 20–30% of patients, recurrent disease is non-progressive193. Thus, rituximab should be withheld in patients with persistent proteinuria at <1 g/day. There is no evidence-based benefit on the post-transplant outcome of treatment with rituximab before transplantation.

Quality of life

Outlook

References

Acknowledgements

L.B. acknowledges institutional funding for the Glomerular Disease Center at Boston Medical Center in support of the preparation of this manuscript. J.W. acknowledges support from grants from the Dutch Kidney Foundation (grant nrNSN 17PhD12), funding from European Union Seventh Framework Programme FP7/2007-2013 grant 305608: European Consortium for High-Throughput Research in Rare Kidney Diseases. V.J. acknowledges research grants from Baxter Healthcare, GSK, and NephroPlus and honoraria/speaker fees from Baxter Healthcare and AstraZeneca (all monies paid to the employer). P.R. acknowledges support from grants from the National Research Agency: MNaims (ANR-17-CE17-0012-01) and SeroNegMN (ANR-20-CE17-0017-01). F.C.F. acknowledges unrestricted research grants from Genentech Inc., Roche and MorphoSys for research on Membranous Nephropathy (all funds paid to the institution). M.V., P.R. and J.W. acknowledge the European Rare Kidney Disease Network (ERKNet). A.T. is supported by a National Health and Medical Research Council Investigator Award (1197324). F.F.H. acknowledges support from the Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (2018GZR0201003).

Author information

Ethics declarations

Competing interests

L.B. is co-inventor on the patent “Diagnostics for Membranous Nephropathy” and has received consultancy fees from Alexion, Ionis, Genentech and Visterra for topics related to membranous nephropathy as well as research support from Sanofi Genzyme and Pfizer. P.R. has received consultancy fees from Alexion and MorphoSys for topics related to membranous nephropathy. F.C.F. has received consultancy fees from Alexion and MorphoSys for topics related to membranous nephropathy. F.F.H. has received consultancy fees from AbbVie and AstraZeneca. J.W. has received consultancy fees from Novartis and MorphoSys for topics related to membranous nephropathy. The other authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Disease Primers thanks L. Barisoni, S. Maruyama and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Content retrieved from: https://www.nature.com/articles/s41572-021-00303-z.

作者：陈晛  李祥炜  何立群  路建饶  陈杰  张传富  韩海燕  朱雪萍

摘要：

朱氏雪萍,弱冠建志岐黄,后师从孟河医派丁氏内科叶景华教授,孜研而笃思,渐得孟河学派治肾之心法。朱氏究学,喜于中西二学间印证阐发,故治技日臻,遂成浦东新区名中医,曾任上海市第七人民医院中医科主任,尤擅治疗糖尿病肾病(DN)。笔者侍诊日久,得见朱师察闻切问,起沉疴于覆手,常有醍醐盈髓之感,今为后学浅剖朱师从”积”论治DN之经验。DN为糖尿病最常见的并发症,早中期不易被察觉,临床仅表现为少至中等量蛋白尿,现代医学认为该病一旦进入Ⅳ期即临床蛋白尿期,其病程将不可阻止及逆转,必然进展至终末期肾病,治疗方面则缺乏特效药物,仅通过控制血糖、血压、血脂、蛋白尿及对症治疗来延缓其发展速度,而中医学者认为,中医

DOI：CNKI:SUN:JXSB.0.2019-02-025

年份：2019

Content retrieved from: https://xueshu.baidu.com/usercenter/paper/show?paperid=ee6a3d34447927a366feed3af2f68821&site=xueshu_se.

【作者单位】上海市第七人民医院肾病科;

Content retrieved from: http://www.cnki.com.cn/Article/CJFDTotal-JXSB201306005.htm.

Content retrieved from: http://www.cnki.com.cn/Article/CJFDTotal-ZYJL201403005.htm.

Content retrieved from: https://www.cnki.com.cn/Article/CJFDTotal-SHZD202303003.htm.

陈杰1,2郑颖3叶玉妹3,2廖琳1胡静1张传富1,2韩海燕1,2陈晛1,2刘文瑞1路建饶1,2叶景华1,3,2

1. 上海中医药大学附属第七人民医院肾病科 2. 叶景华全国名老中医传承工作室  3. 上海中医药大学附属第七人民医院传统医学示范中心

摘要：目的:观察内服肾衰方联合肾衰膏脐疗以及降酐合剂灌肠的中医内服外治综合方案对于毒邪蕴结型慢性肾衰竭的疗效,并从炎症、氧化应激角度探讨其作用机制。方法:将毒邪蕴结型的慢性肾衰竭患者100例,随机分为两组各50例,对照组采用西医基础治疗,治疗组在西医基础治疗的基础上,辅以中医内服外治方案,即每日煎服肾衰方联合隔日1次肾衰膏外敷神阙穴,以及隔日1次降酐合剂保留灌肠,疗程2月,观察治疗前后证候疗效、肾功能、炎症因子及氧化应激的变化。结果:两组共完成病例92例,对照组47例,治疗组45例,治疗组治疗后的总有效率91.1%,优于对照组的74.5%(P <0.05);治疗组治疗后BUN、Scr、UA较对照组明显下降,e GFR则有所上升(P <0.01);治疗组治疗后炎症因子MCP-1、TNF-α、IL-1β、IL-6以及氧化应激反应指标MDA、AGEs均低于对照组(P <0.05)。结论:该方案能够有效缓解毒邪蕴结型肾衰竭患者症状,改善肾功能,并减轻炎症及氧化应激反应,同时这也是该方案的作用机制之一。

关键词：肾衰方; 肾衰膏; 降酐合剂; 炎症因子; 氧化应激;

基金资助：上海市科学技术委员会科研项目(No.17401931800)； 上海市浦东新区临床中医高峰学科(No.PDZY-2018-0601)；

专辑：医药卫生科技

专题：中医学

分类号：R277.5

Content retrieved from: https://kns.cnki.net/kcms2/article/abstract?v=RyaFSLOYMk7vskSIgT8rhOTWHhshmpet38kHtQp5ItbKXQZ2ltZf17os1ZbR81QMNa-j47BqdYFwGc43z6IV-FzN9-XKaCj4P3FuPJC0CcfE-iAb7t4SOVXTC85rtOpc5-005quQAiPjFXJ93hsDPA==&uniplatform=NZKPT&language=CHS.

患者信息：李某，女，65岁

初诊：2022年8月22日

主诉：发现血尿4年余

现病史：2018年5月8日因感寒至当地医院就诊，查尿常规提示尿隐血：（+++），尿蛋白（+++），2013年8月22日24h蛋白尿定量0.734g。肾功能：尿素氮：6.5mmol/L，肌酐74μmol/L，血尿酸304μmol/L。双肾动脉彩超提示双肾动脉未见狭窄，血流通畅。患者一直在当地医院就诊，期间服用中药及中成药（具体用药剂量不详），症情有所缓解。2022年6月7日就诊于上海交通大学附属瑞金医院，查尿常规：尿潜血（+++），尿红细胞（+++），尿蛋白（++）。24h蛋白尿定量1.765g，尿素氮：8.5mmol/L，肌酐104μmol/L，血尿酸504μmol/L。肾活检组织学报告：IgA肾病（局灶节段硬化），Oxford评分：M0、E0、S1、T0。诊断为IgA肾病，予对症治疗后，病情未明显缓解。2022年8月22日前来就诊。

症见：精神疲倦，腰部酸软，纳可，眠欠佳，双下肢轻度凹陷性水肿，夜尿2次，手足心出汗，肉眼血尿，尿中泡沫，舌淡红，有裂纹，苔微腻，脉沉滑。

诊断：

西医诊断：IgA肾病（局灶节段硬化）

中医诊断：尿血（脾肾两虚，湿浊内阻）

治则：补益脾肾，利湿化浊

方药：童氏健脾益肾方加减

处方：

7剂，每日1剂，水煎早晚温服。

二诊：2022年8月30日

症见：精神疲倦，腰部酸软，手足心出汗等症状较前明显改善，尿中泡沫仍多，双下肢轻度凹陷性浮肿，舌淡红，有裂纹，苔微黄腻，脉沉滑。尿常规：尿红细胞（++），尿潜血（+），尿蛋白（++），24h蛋白尿定量1.325g。肾功能：尿素氮：7.3mmol/L，肌酐94μmol/L，血尿酸404μmol/L。

辩证：脾肾两虚，湿热内阻

处方调整：上方去藿香、佩兰， 加半夏9g、蝉蜕6g、蚕茧壳9g、薏苡根30g

按语：

患者年过六旬，卫气不固，外邪入侵，病邪由表及里，损伤脾肾，肾脏封藏失职，不能固摄，脾气升清功能失调，营养精微物质不能布散全身，清阳下陷，精微外流，予以童氏健脾益肾方加减补益脾肾，利湿化浊，以达固摄精微，培补先后天。服药7剂，尿浊仍在，续用化浊固摄之药；潜血得减但犹存，续用敛血之品；但患者体质湿热，滋腻太过，加之补阳之药化热，宜稍减而不碍本意；其余症状均比之前改善，配伍得当，诊治见效，续用。兼顾肺脾肾三脏，注重阴阳表里的调和，扶助正气的同时，兼顾邪实的存在，使得脾气复升、肾得固摄，故尿血得以改善。

患者信息：林某，女，55岁

初诊：2022年8月30日

主诉：腰酸伴泡沫尿3年余，加重1周

现病史：3年前患者因过度劳累后出现腰酸伴泡沫尿，遂至当地医院就诊，西医诊断慢性肾炎，服用西药治疗后症状减轻，未予重视。一周前因劳累，出现腰痛、双眼睑、双下肢浮肿，逐渐加重，来院查尿常规：尿蛋白（+++），24h微量蛋白2.273g，肾功能正常。 有糖尿病病史5年余，目前胰岛素治疗；高血压病史30年，目前服用拜新同。空腹血糖13.2mmol/L。

刻诊：患者腰痛腰酸，神疲乏力，肢体浮肿，乏力明显，小便短少，大便溏稀，舌胖大， 质淡，苔黄腻，舌下络脉青紫，脉沉细无力

诊断：

西医诊断：慢性肾炎

中医诊断：水肿病（脾肾两虚，兼风湿瘀滞证）

治则：健脾化湿，温肾固精，祛风通络

处方：

14剂。每日1剂，水煎2次，取汁混合，分2次早晚温服。 并嘱其饮食调理，低脂、低糖、低盐、优质蛋白质饮食，避免劳累和感冒，不要熬夜、按时起卧，适度节制性生活。

按语：

本医案中患者感受风邪，内舍于肺，肺失宣降，水道不通，以致风水相搏，泛滥肌肤，故见双眼睑及下肢浮肿。患者中阳不振，健运失司，运化失常，以致下焦水邪泛滥，脾升清运化功能失调，则体内水湿代谢异常，日久湿邪内停，且湿性重浊、极易困脾、故见腰以下尤甚，脾虚生湿，运化无力，故见大便溏薄，舌苔厚腻：脾虚气血生化乏源，阳不温煦，故见神疲乏力；水湿之邪，浸渍肌肤，壅滞不行，以致肢体浮肿不退，水湿日增而无出路，横溢肌肤，所以肿势日重。脾肾两虚，水液运行失其常道，故见双足浮肿，日久血瘀，故见腰痛腰酸，舌下络脉青紫；脉沉细无力，乃是脾肾两脏亏虚，湿热瘀滞之象。

患者信息：孙某，男，80岁

初诊：2022年09月16日

主诉：肌酐升高8年余，乏力纳差1周

现病史：患者2014年因痛风就诊于我科，入院完善相关检查，查（2014-03-26）ECT：左侧肾小球滤过功能轻度受损，右侧肾小球滤过功能正常（左肾GFR31.9ml/min，右肾GFR37.94ml/min，总GFR69.83ml/min），（2014-4-2）血常规：WBC5.08×10^9/L，N53.1%，HB139g/L，CRP：5mg/l；肾功能：尿素氮5.86mmol/L，肌酐82.6umol/L，尿酸497.2umol/L，胱抑素C1.09mg/L；电解质：血钙2.6mmol/L，诊断慢性肾脏病2期。后未定期门诊随访。1周前患者无明显诱因下出现乏力纳差，休息后未见明显缓解，遂就诊于金高中西医结合医院，查肾功能（2022.09.09）：肌酐182，UA 660，BUN 12.33。现患者为求进一步诊疗，由门诊拟“慢性肾脏病4期”收治入院。患者既往有高血压病40余年，最高血压180+/100+mmhg，目前口服可多华、替米沙坦氢氯噻嗪、美托洛尔、吲达帕胺控制血压，血压控制欠佳。有冠心病病史，口服单硝酸异山梨酯、阿托伐他汀治疗。有前列腺增生病史。2015年行右侧甲状腺切除术。

刻诊：面色萎黄，肢体困重，胸闷气急，腰酸乏力，纳呆泛恶，夜寐欠安，小便短少，夜尿频数，大便干结。舌淡胖，舌下脉络迂曲，苔少，脉沉细。

诊断：

西医诊断：1.慢性肾脏病4期2.冠状动脉粥样硬化性心脏病3.痛风4.高血压病3级（极高危）5.前列腺增生

中医诊断：肾衰病（脾肾亏虚，瘀血内阻）

治则：补益脾肾，活血化瘀

处方：

14剂，每日1剂，水煎2次，取汁混合，分两次早晚温服。并嘱其饮食调理，低脂、低糖、低盐、优质蛋白质饮食，避风寒，慎起居，调饮食，畅情志

方解：该方中以党参补中益气，黄芪补气升阳，赤芍清热凉血，白芍养血调经，当归补血活血，熟大黄峻下攻积，王不留行活血通经，车前子利尿通淋，芥子温肺化饮，白术补气健脾，防风祛风解表，猪苓利水渗湿，白茯苓益气健脾，金蝉花祛风益肾，牛膝补肝肾，强筋骨，桃仁活血祛瘀，红花祛瘀止痛，丹参凉血消痈，蒲公英、白花蛇舌草清热解毒，肉苁蓉补肾阳，菟丝子补肾固精，芡实益肾固精，覆盆子固精缩尿，陈皮理气健脾，佛手疏肝解郁，苍术燥湿健脾。

按语：

慢性肾脏病发展至终末期，病因多涉及多个脏腑，病机比较复杂。病危在肾而又与脾胃密切相关。在病机的认识上多是以脏腑虚损（脾肾）而复感外邪，加之情志、劳累等因素，而致正气虚损，浊邪塞滞。针对于这样的患者，何立群教授长期临床经验总结肾病一号方、二号方拟做底方。一号方多适用于脾肾亏虚，正虚为主的患者，二号方适用于邪盛为主。邪实多见于内外风、水湿、浊毒、瘀血等。该病人以二号方为底，以其大便干结而浊毒内盛为主。加之患者瘀血内阻，辅之以活血化瘀、健脾理气。

　　中新网上海新闻5月29日电（陈静 司春杰）沪滇协作对口医疗帮扶推出新模式。记者29日获悉，上海市第七人民医院“上海工匠禹宝庆云工作室”“上海市名中医何立群云工作室”“‘三七花开’云科普基地”在云南大理州巍山县人民医院揭牌。
　　这意味着，除了每年驻点派驻专家进行医疗帮扶外，上海工匠、市七医院骨科专家禹宝庆及上海市名中医何立群及其团队将通过“云端”为当地提供专业服务和指导，双方还将在医疗科普方面进一步合作。

　　禹宝庆教授是人民名医、上海市领军人才、上海工匠，从事骨科临床工作30余年，在骨科各种疑难杂症诊治，运动医学、创伤骨科、关节外科、脊柱外科等方面具有较高的造诣。“上海工匠禹宝庆云工作室”的成立将以“云”问诊、“云”带教等形式，促进上海市第七人民医院优质的骨科医疗资源及强大的医疗团队实现互利共享。

　　作为“上海市名中医何立群云工作室”的揭牌代表，市七医院肾病科胡静主任表示，何立群教授是第七批全国名老中医药专家学术经验继承工作指导老师，是上海市领军人才，在慢性肾炎、尿毒症、尿路结石等疑难杂症诊治方面颇有建树，双方将借助本次云工作室的落地，把上海市第七人民医院的特色技术、优质资源带到巍山县人民医院。
　　“‘三七花开’科普云基地”将依托上海市第七人民医院云展厅、“三七花开”科普平台，充分挖掘云南省优质的中草药天然资源，双方将通过联动，进一步推广中医药在疾病防治和诊疗中的作用，让中医药发展普惠更多百姓。

　　自2021年11月以来，上海市第七人民医院接力帮扶巍山县人民医院，从人才培养、学科建设、学术交流等方面给予援助和支持，做了一系列积极而富有成效的工作。截至目前，七院共派驻6批17位专家开展驻点巍山帮扶工作。巍山也选派了业务骨干6批12人次到七院进修学习，同时乡镇及其他县级医院选派骨干到县人民医院向上海驻点专家跟班学习，使县公立医院技术水平得到有效提高，业务骨干得到培养，学科建设步入快车道。
　　在揭牌仪式上，巍山县委常委、县政府黄坚副县长致辞。他表示，上海专家工作室和科普基地在巍山的落地，举行对口帮扶暨授牌仪式，标志着两地的合作迈入了新的阶段。巍山县将以此为契机，进一步加强沟通交流，深化合作领域，拓展合作成果；将认真学习借鉴上海市第七人民医院的先进经验和特色技术，不断提升自身的医疗水平和服务能力。县人民医院要加强与上海市第七人民医院的沟通和协调，强化交流互动，增强双方感情，建立长期、紧密的帮扶关系。对口帮扶是一项长期而艰巨的任务，在上海最顶尖的医院医护人员及管理团队的帮助指导下，在巍山县医护人员的共同努力下，沪滇对口帮扶工作将再创佳绩，巍山县医疗卫生健康事业一定能够迎来更加美好的明天。
　　巍山县人民医院刘钟院长汇报帮扶工作开展情况。自20世纪50年代起，上海市就组建了医疗团队到巍山开展对口帮扶工作，同巍山结下了深厚的情谊。2021年，上海市第七人民医院接过了帮扶的“接力棒”，与巍山县医院签署了对口帮扶协议，此后，七院党政领导班子多次带队到院调研指导，进一步加强了县医院在人才培养、设施设备、学科设置、医疗技术、医疗质量等方面的建设，全方位提升了医院的医疗服务水平。驻点帮扶专家们充分发挥自身的专业特长，助力县医院康复医学科、神经外科等专科建设及特色技术开展。
　　上海市第七人民医院禹宝庆院长表示，上海市第七人民医院从一家二级综合医院转型为三级甲等中西医结合医院，一路走来可谓筚路蓝缕。目前，医院的医疗、教学、科研正“加速度”发展，在做深做实中医内涵的同时，还在把西医做大做强，除了拥有4个国医大师工作室、14个省部级名中医工作室等，七院今年积极响应浦东新区卫健委的学科建设，4个学科进入新质专科，数量在全区排名第二，将借助学科建设的巨大利好政策，努力在中西医结合方面做出亮点、做出成绩。自2023年以来，七院通过资源重整，“下好先手棋”，加快医工交叉、医产融合发展，陆续与苏州科技大学成立数智医学研究院，与上海理工大学成立教育部医用光学技术与设备重点实验室——上海市第七人民医院分中心，与上海长三角技术创新研究院共同打造医疗数据要素X联合实验室，加速医学成果转化工作，让医患多方共同受益。希望七院优质的中、西医资源能够带到巍山县，让医院共享，让百姓享福。巍山县能够进一步“走出去、请进来”，期待在上级部门的引领和支持下，七院能与巍山县携手把沪滇合作做得更扎实，助力当地医院真正实现高质量发展。

　　为进一步加强沪滇合作与交流，让巍山县百姓就近就享受优质医疗服务，由市七医院大外科主任赵滨，骨科常务副主任(主持工作)、关节外科主任刘丙立，妇产科主任李林霞，肾病科主任胡静，康复医学科(康复治疗科)副主任于小明等组成的专家团队于当天下午在巍山县人民医院开展手术带教及现场坐诊。“我自己长年患有骨痛，听说今天有上海来的专家，特意过来看一看，感谢政策、感谢好资源，希望以后经常有这样的活动。”一位来自巍山县白族居民激动地说。
　　当天，上海市第七人民医院院长禹宝庆携党政办、医务处、护理部、质控办、骨伤科、大外科、妇产科、肾病科、康复医学科等各科室主任；巍山县委常委、县政府黄坚副县长，县卫生健康局主要领导、分管领导，县人民医院党政班子成员和巍山县巨丰农业开发有限公司负责人等共同见证了此次揭牌仪式。
　　如今，借助沪滇合作的东风，巍山同上海市第七人民医院搭建起新一轮的友谊桥梁，我们坚信，在上海市第七人民医院强大的模范引领和技术依托下，通过持续开展沪滇对口帮扶活动，将为当地县人民医院的可持续发展注入强劲的动力，助推全县卫生健康事业高质量发展。

【成份】

山药块茎含薯蓣皂甙元(diosgenin)0。012%，多巴胺(dopamine)，盐酸山药碱(batatasine hydrochloride)，多酚氧化酶(polyphenoloxidase)，尿囊素(allantoin)止杈素(abscisin)Ⅱ。

又含糖蛋白(glucoprotein)，水解得：赖氨酸(lysine)，组氨酸(histidine)，精氨酸(arginine)，天冬氨酸(aspartic acid)，苏氨酸(threonine)，丝氨酸(serine)，谷氨酸(glutamic acid)，脯氨酸(proline)，甘氨酸(glycine)，丙氨酸(alanine)，缬氨酸(valine)，亮氨酸(leucine)，异亮氨酸(isoleucine)，酷氨酸(tyrosine)，苯丙氨酸(phenylalanine)和蛋氨酸(methionine)。

还含包括上述氨基酸和胱氨酸(cystine)，

γ-氨基丁酸(γ-aminobutyric acid)在内的自由氨基酸，另含具有降血糖作用的多糖，并含由甘露糖(mannose)，葡萄糖(glucose)和半乳糖(galactose)按摩尔比6.45：1：1.26构成的山药多糖，又含钡、铍、铈、钴、铬、铜、镓、镧、锂、锰、铌、镍、磷、锶、钍、钛、钒、钇、镱、锌、锆以及氧化钠、氧化钾、氧化铝、氧化铁、氧化钙、氧化镁等。根茎含多巴胺、儿茶酚胺(catecholamine)，以及胆甾胆碱醇(cholesterol)，麦角甾醇(ergosterol)，菜油甾醇(campesterol)，豆甾醇(stigmasterol)，β-谷甾醇(β-sitosterol)。粘液中含植酸(phytic acid)，甘露多糖(mannan)Ia,Ib和Ic;有人说粘液含多糖40%，蛋白质2%，磷3%和灰分24%，多糖部分由80%的甘露糖和少量的半乳糖，木糖(xylose)，果糖(fructose)及葡萄糖所组成。珠芽(零余子)含5种分配性植物生长调节剂，命名为山药素(batatasin)Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ。

还含止杈素，多巴胺和多种甾醇：胆甾烷醇(cholestanol)，(24R)-α-甲基胆甾烷醇[(24R)-α-methyl cholestanol]，(24S)-β-甲基胆甾烷醇[(24S)-β-methyl cholestanol]，(24R)-α-乙基胆甾烷醇[(24R)-α-ethyl cholestanol]，胆甾醇，菜油甾醇，(24S)-β-甲基胆甾醇[(24S)-β-methyl cholestanol]，24-亚甲基胆甾醇(24-methylenecholesterol)，β-谷甾醇，豆甾醇，异岩藻甾醇(isfucosterol)，赬桐甾醇(clerosterol)，24-亚甲基-25-甲基胆甾醇(24-emthylene-25-methyl cholesterol)，7-胆甾烯醇(lathosterol)，8(14)-胆甾烯醇[cholest-8(14)-enol]，(24R)-α-甲基-8(14)-胆甾烯醇[(24R)-α-methyl cholest-8(14)-enol]，(24S)-β-甲基8(14)-胆甾烯醇[(24S)-β-methyl cholest-8(14)-enol]，(24R)-α-乙基-8(14)-胆甾烯醇[(24R)-α-ethyl cholest-8(14)-enol]。

同属植物日本薯蓣块茎含三萜皂甙，尿囊素，胆碱(choline)，17种氨基酸(比山药块茎所含的自由氨基酸缺γ-氨基丁酸)及无机化合物(比山药块茎所含的无机化合物缺镧)。又含修养降血糖活性的日本薯蓣多糖(dioscoran)A、B、C、D、E、F。

Content retrieved from: http://ypk.39.net/c518819/.

简介：

黄芪是多年生高大草本植物，属于豆科。夏季开花，结荚果。根很长，一般采挖4年以上的根。除去地上茎叶及须根，晾干后截成一二尺长收藏或切片药用。在秋季采收的黄芪含微量元素硒(Se)较多，因而质量较好。多种黄耆属植物在各产地亦同供药用，如春黄耆(又名藏黄耆)(西藏)、云南黄耆(西藏、云南)、弯齿黄耆(云南)、阿克苏黄耆(新疆)等。

形态：

黄芪直根圆柱形、有的有分枝，上端较粗，长30～90厘米,直径1～3.5厘米，表面纵皱色淡棕黄色或淡棕褐色，有不整齐的纵皱纹或纵沟质，硬而韧有粉性，皮部黄白较疏松；木部菊花纹理状，气似豆腥味微甜。老根中心偶有枯朽状,黑褐色或呈空洞。气微,味微甜，嚼之微有豆腥味。质量以根条粗长、菊花心鲜明、空洞小、破皮少者为佳。

产地：

古代黄芪正品的产地有从四川、甘肃，经宁夏、陕西，向山西、内蒙古逐渐过渡的情况，至清代时黄芪的道地产区已转移至山西、内蒙，这与现今黄芪的主产区相一致。

性状：

性味：甘，微温。

归经：归肺、脾、肝、肾经。

功效：

补齐固表，托疮生肌，黄芪含皂甙、蔗糖、多糖、多种氨基酸、叶酸及硒、锌、铜等多种微量元素。是用作增进能力和抵抗疾病的良药，有增强机体免疫功能、防癌、保肝、利尿、抗衰老、抗应激、降压和较广泛的抗菌作用。

1. 防癌

黄芪含有微量元素硒，硒是癌症的天敌，所以黄芪有抗癌作用。

2. 抗肿瘤

黄芪中有效成分黄芪多糖与抗肿瘤药物合用有增效减毒之功，即增强抗癌效果，减轻副作用。

3.益气固表
生用黄芪，有益气固表、利水消肿、脱毒、生肌的功效，适用于自汗、盗汗、血痹、浮肿、痈疽不溃或溃久不敛等症。
4.补气养血
蜜炙黄芪有补气、养血、益中功效，适用于内伤劳倦、脾虚泄泻、气虚、血虚、气衰等症。
5.降血压
现代医学证明，黄芪具有降低血液黏稠度、减少血栓形成、降低血压、保护心脏、双向调节血糖、抗自由基损伤、抗衰老、抗缺氧、抗肿瘤、增强机体免疫力作用，可用来治疗心脏病、高血压、糖尿病等症。黄芪还能扩张血管，改善皮肤血液循环和营养状况，故对慢性溃疡久不愈合者有效。其还能消除肾炎患者的蛋白尿，保护肝脏，防止肝糖原减少。

主治体虚自汗，久泻，脱肛，子宫脱垂，慢性肾炎，体虚浮肿，慢性溃疡，疮口久不愈合。

禁忌：

1、从体质上来说，黄芪最适合气虚脾湿型的人，这种人往往身体虚胖，肌肉松软，尤其是腹部肌肉松软。而身体十分干瘦结实的人则不宜。从身体状况来说，感冒、经期都不要吃黄芪。

2、从季节来说，普通人春天不宜吃黄芪。春天是生发的季节，人体需要宣发，吃黄芪就不太适宜了。

3、肾病属阴虚，湿热、热毒炽盛者用黄芪一般会出现毒副作用，应禁用。因为黄芪性味甘、微温，阴虚患者服用会助热，易伤阴动血；而湿热、热毒炽盛的患者服用容易滞邪，使病情加重。如果必须服用黄芪，一定要配伍运用。

4、阴虚患者使用黄芪，必须配伍养阴药使用，如生地、熟地、玄参、麦冬、天冬、玉竹等。湿热患者必须配伍清利湿热药，如黄连、茵陈、黄芩等。热毒炽盛的患者必须配伍清热解毒药，如黄连、栀子、大黄、败酱草等。

西方最新研究的结果也证实，服用黄芪的时候，最好不要服用环磷酰胺5，否则互相会相克。另外，有一些品种有一定的毒性，所以不能随便服用，服用量最好根据医生的医嘱。

食疗方法：

【党参黄芪炖鸡】

材料：母鸡，党参，黄芪

做法：

1.将母鸡下沸水锅中焯去血水、洗净；将红枣洗净、去核；将党参、黄芪用清水洗净、切段。

2.将鸡放入炖盅内，加适量水，放入党参，黄芪、红枣、料酒、精盐、味精、姜片，放入笼内蒸至鸡肉熟烂入味，取出即成。

功效：有健脾胃、补气益血、提高人体免疫力、强壮身体、延年益寿等作用。

【党参黄芪粥】

材料： 党参15克，黄芪15克，山药30克，粳米60克。
做法： 将党参、黄芪（用纱布包好）、粳米、山药洗净；全部用料一起下锅，加清水适量，文火煮成粥即可（弃黄芪包）。随量食用。
用法： 饮汤食肉，佐餐食用。
功效： 益气补虚，健脾和胃。适用于胃及十二指肠溃疡属脾胃虚弱者。症见胃脘疼痛，体弱食少，而色萎白，脉虚弱等。本粥是滋养健胃之品。

Content retrieved from: http://zy.china.com.cn/2023-08/04/content_98467673.html.

【作者单位】：上海市第七人民医院

Content retrieved from: http://cpfd.cnki.com.cn/Article/CPFDTOTAL-ZGZP200303002183.htm.

会议议程

主办单位：
上海市第七人民医院何立群名中医工作室
浦东新区医学会中医肾病专委会
时间：
2023年10月7日—10月9日
地点：
上海市浦东新区大同路358号学术会议中心第三会议室
出席领导及嘉宾：
浦东新区卫生健康委员会副主任    郁东海
浦东新区医学会会长    顾建钧
上海市第七人民医院院长    禹宝庆
上海市医学会肾脏病分会第十二届委员会主任委员   汪年松

讲课日程表

糖尿病肾病从机制到临床转化启示

讲者：汪年松；主持：蒋更如

汪年松

上海交通大学附属第六人民医院肾脏科主任
博士、主任医师、二级教授、博士生导师
上海市领军人才、 国务院政府特殊津贴专家
上海医学会肾脏病分会主任委员
上海医院管理协会血液净化分会副会长
上海医师协会内科分会副会长
中华肾脏病学会全国委员
中国中西医结合肾病学会常委
中国医师协会肾脏病分会常委
中国医院管理协会血液净化分会常委
世界华人肾脏病学会常委

蒋更如

上海交通大学医学院附属新华医院肾脏科
博士，主任医师，教授，博士研究生导师
肾脏科主任，内科教研室主任，上海市罕见病诊治中心主任
上海市医学会肾脏病分会主任委员
上海市医师协会肾脏内科医师分会副会长
中华医学会肾脏病分会常委
中国医师协会肾脏内科医师分会常委
中国医院协会血液净化中心管理分会常委
中国医药卫生文化协会肾病与血液净化专业委员会副主任委员
AJKD, JASN，Nature Reviews Nephrology中文版, 上海医学杂志编委
主要研究方向：IgA肾病、MN的临床和基础研究及终末期肾衰竭透析患者心血管事件的防治研究
承担10余项国家和上海市课题，发表论文100余篇

血透通路失功后外科干预方案与临床体会

讲者：张岚；主持：漆映辉

张岚

上海交通大学医学院附属仁济医院血管外科科主任
博士，硕士生导师

学术任职：
中华医学会外科学分会血管外科学组委员
上海市医学会血管外科专科分会副主任委员
中国医疗保健国际交流促进会血管外科学分会副主任委员
中国医师协会血管外科医师分会常务委员
上海市医师协会血管外科医师分会副会长
中国老年医学学会周围血管疾病管理分会副会长

透析通失功的外科治疗下载课件

漆映辉

主任医师，医学硕士
上海市浦东新区浦南医院肾脏内科常务副主任
中国中药协会肾病中药发展研究专业委员会委员
中国非公立医疗机构肾脏病透析专业委员会委员
上海康复学会肾脏康复委员会委员
上海医院管理学会血液净化管理委员会委员
上海市中西医结合学会肾脏专业委员会秘书
上海市中西医结合学会诊断专业委员会副主任委员
在肾脏内科临床工作近30年，擅长慢性肾脏病的早期防治及肾功能衰竭的透析治疗。

---

何立群教授治疗慢性肾脏病经验

讲者：张昕贤；主持：徐旭东

张昕贤

主任医师
临床科室：肾病科
研究方向：中西医结合治疗肾脏病
世界中医药联合会医案专业委员会常务理事
世界中医药联合会临床用药安全委员会理事
中华中医药学会内科分会委员
中华中医药学会肾病分会委员
中国中西医结合学会肾病分会青年委员
中国民族医药促进会肾病分会委员
上海市中西医结合学会肾病分会委员
上海市中医药学会肾病分会常委务委员兼秘书
主持参与科技部慢性肾脏病行业专项、上海市中医临床肾病基地建设、海派名医童少伯学术思想研究、上海中医药研究重点研究项目等多个国家级、省部级项目，获得教育部科学技术进步奖、中华中医药学会科学技术奖、上海市科学技术奖一等奖、上海医学科技奖、上海市科技进步奖等多个奖项。

何立群教授治疗慢性肾病经验（张昕贤）下载

IgA肾病的中医药治疗

讲者：王怡；主持：胡静

王 怡

主任医师、教授，博士生导师
上海中医药大学附属岳阳中西医结合医院肾病科主任、中医内科学教研室副主任
中华中医药学会肾病分会 常务委员
上海中医药学会肾脏病专业委员会 副主任委员
上海中西医结合学会肾脏病专业委员会 副主任委员
上海中西医结合学会血液净化专业委员会 副主任委员
上海中西医结合学会器官纤维化专业委员会副主任委员
上海市康复医学会肾脏康复专业委员会 副主任委员
上海市医师协会肾脏内科医师分会 委员
上海市医学会肾脏病专科分会 委员
获上海市科技进步三等奖、上海市中西医结合科技奖一等奖、三等奖等，主持国家自然基金2项、上海市科委课题5项，发表学术论文100余篇, 其中SCI收录10余篇

王怡-IgA肾病的中医治疗下载

胡静

教授、主任医师、硕士生导师
国家中医药管理局“十二五”重点建设专科（肾病） 、上海市肾病优势专科科室科主任
2022首届中国人口文化促进会国医名师学术经验传承工作委员会副会长
上海市中医药学会第十届肾病分会常务委员
世界中联临床用药安全研究专业委员会第二届理事会常务理事
上海市浦东新区医学会中医肾病专业委员会主任委员
中国民族医药学会肾病分会理事
中国非公医疗机构协会肾脏病透析专业委员会第二届委员会委员
上海电视台“X诊所”节目特约中医专家
从事肾病科临床和基础工作30余年，在中西医药防治慢性肾脏疾病的临床诊疗和科学研究方面取得显著的成绩。先后主持和参加上海市以及浦东新区10余项课题研究，主编肾病学科及中医学科专著6部。近5年发表专业论文21篇，其中核心期刊17篇，SCI文章5篇。获得浦东新区科学技术进步、上海中西医结合科学技术三等奖各1项。国家知识产权局授权专利3项。

讲者：叶朝阳；主持：赵俊丽

难治性肾病综合征中西医结合治疗进展

叶朝阳

上海曙光医院二级教授、主任医师、博士生导师
上海中医药大学肾病研究所所长
教育部肝肾疾病病症重点实验室 副主任
上海中西医结合学会血液净化专委会 主任委员
中国非公医协肾脏病学会血管通路委员会 主任委员
中国血液净化管理分会委员 血管通路学组副组长
中国中西医结合肾脏病分会 委员
世界华人肾脏医师协会 委员
上海市中西医结合代谢与免疫肾病专委会 副主任委员
6本杂志编委, Hemodialysis Int. JVA，Renal Fail. Frontiers of medicine, Nephrology等审稿人
发表学术论文260余篇， 发表SCI论文50余篇，主持国家自然基金等科研项目14项，主编专著9部，国家发明专利和实用新型专利 8项 ，第1申请人和主要申请人获得 国家和省部级二等以上成果奖 6项

难治性肾病的中西医结合诊治2023下载

赵俊丽

博士、主任医师、硕导
浦东新区周浦医院肾内科主任
中华医学会肾脏病分会第九届青年委员
上海市医院协会血液净化管理专业委员会委员
上海市中西医结合学会第七届肾病专业委员会委员
上海市中西医结合学会第一届代谢与免疫肾病专业委员会委员
中国非公立医疗机构协会肾脏病透析专业委员会临床肾脏病学组委员
上海市医学会肾脏康复委员会委员
主持完成国家自然科学基金课题1项，省级课题3项，区级课题3项，发表论文30余篇，其中SCI收录7篇

健脾清化方治疗慢性肾脏病肾纤维化免疫炎症损伤的作用机制

讲者：何立群；主持：陆任华

何立群

医学博士、二级教授、主任医师、博士生导师、博士后合作导师
全国卫生系统优秀工作者，上海市劳动模范
第七批全国老中医专家学术经验继承工作指导老师、上海市名中医、上海市领军人才
国家临床重点专科、教育部重点学科（肾病）、教育部重点实验室（肾病）、国家中医药管理局肾病重点学科和专科、上海市重点学科（肾病）、上海市教委肾病创新团队带头人
中华中医药学会内科分会副主任委员
世界中医药联合会医案分会副会长
中国民族医药学会肾病分会副会长
中国医药教育协会中医药教育促进工作委员会副主任委员
中国中西医结合学会肾脏专业委员会常委，上海市副主委
上海市中医药学会常务理事
上海市中医药学会肾病分会主任委员
上海市中医肾病临床研究基地、海派名医童少伯研究基地负责人
从事肾病科临床和基础工作30余年，在中西医药防治慢性肾脏疾病的临床诊疗和科学研究方面取得显著的成绩。先后主持国家及上海市重大科研项目18项。以第一或通讯作者发表论文430余篇，其中SCI收录的英文论文38篇，影响因子总和80多分。主编专著8部，参编6部。作为第一完成人获教育部、上海市、中国中西医结合学会、中华中医药学会科技进步、上海市医学会二等奖11项，上海市中西医结合学会、中医学会一等奖各1项，国家知识产权局授权专利8项。

何立群—健脾清化方治疗慢性肾脏病肾纤维化免疫炎症损伤的作用机制下载

陆任华

上海交通大学医学院附属仁济医院 肾脏科
医学博士，主任医师，意大利国际肾脏病研究所(IRRIV) 访问学者
中国老年医学学会周围血管疾病管理分会 委员
中国非公立医疗机构协会肾脏病透析专业委员会 委员
中国医疗保健国际交流促进会血管外科分会血透通路学组 青年委员
上海市医院协会第一届医院血液净化管理专业委员会 青年委员
上海市康复医学会肾脏康复专业委员会 委员
上海市血液透析质量控制督导组 专家成员
上海市浦东新区医学会中医肾病专业委员会 副主任委员
上海交通大学医学院附属仁济医院伦理委员会 委员
居家血液透析(HHD)培训中心 副主任
Nephrology Dialysis Trasplantation，Blood Purification，Renal Failure等杂志审稿人，参与编写Critical Care Nephrology，<血液净化技术书>，<院士名医点评丛书>，<内科疾病诊治方略>等书籍
承担省部级等课题7项，发表SCI论文20余篇，核心期刊论文30余篇
获得第八批省市优秀援疆干部人才，并记功一次

基于“真实世界”临床研究探讨“斡旋三焦”治肾理论在糖尿病肾病中的应用

讲者：王琳；主持：姜威

王琳

医学博士
教授/主任医师
上海中医药大学附属龙华医院肾病二科主任
上海中医药大学附属龙华医院名中医
陈以平全国名老中医学术传承工作室负责人
中国中医药信息学会肾病分会副会长
中华中医药学会免疫学分会常务委员
上海市中医药学会肾病分会常务委员
继承发扬名老中医学术经验与思想，研究成果先后获得上海市科技进步一等奖等省市级奖励八项
近年来，入选上海市中医药高层次人才引领计划，先后获得上海市科技启明星，上海市优秀青年医学人才称号；主持国家自然科学基金项目及多项上海市申康、上海市科委等省市级科研项目十余项。
发表国内外学术论文近百余篇，以执行主编等身份撰写参编名老中医临证经验论著五部

上海龙华王琳-基于“真实世界”临床研究探讨“斡旋三焦”治肾理论在糖尿病肾病中的应用下载

姜威

医学硕士，主任医师，上海中医药大学兼职副教授
上海市浦东新区中医医院肾病科主任
浦东新区卫健委学科带头人
第六批全国老中医药专家学术继承人，师从上海市名中医陈以平教授。
主要学术任职：中国中医药信息学会肾病分会常务理事，中华中医药学会慢病管理分会委员，世界中医药联合会中医疗养专委会理事，上海市中医药学会肾病分会委员，上海市中医药学会补肾活血法分会委员，上海市医师协会中医医师分会委员，浦东新区肾内科专委会委员。主持市、局级科研项目5项，参编著作一部，核心期刊发表论文18篇。

全自动腹膜透析中国专家共识

讲者：郭志勇；主持：姜威

郭志勇

主任医师、教授，医学博士，博士生导师
海军军医大学第一附属医院（上海长海医院）肾内科主任
中华医学会肾脏病学分会 委员
全军肾脏病专业委员会 副主任委员
上海肾脏病专科分会委员会 候任主任委员
中国医师协会整合肾脏病学专委会 副主任委员
中国医师协会肾脏内科医师分会 常务委员
中国中西医结合肾病专业委员会 常务委员
长期主要从事于慢性肾脏疾病早期综合防治、梗阻性肾病、腹膜透析、肾移植。主编专著3部，在国内外核心杂志上发表论文200余篇，分别获国家自然科学基金、军队“十一五” 科研基金、上海科委基础研究重点项目、上海市科委中药领域科技支撑项目、上海市教委科研创新重点基金、上海市自然科学基金等多项基金资助，获上海中西医结合科学技术奖 一等奖，上海医学科技奖二等奖、军队科技进步二等奖一项、 科技进步三等奖二项、军队医疗成果二等奖一项、军队医疗成果三等奖二项。

自动化腹膜透析中国专家共识-第七人民医院肾内科学习班2023.10.7下载

姜威

医学硕士，主任医师，上海中医药大学兼职副教授
上海市浦东新区中医医院肾病科主任
浦东新区卫健委学科带头人
第六批全国老中医药专家学术继承人，师从上海市名中医陈以平教授。
主要学术任职：中国中医药信息学会肾病分会常务理事，中华中医药学会慢病管理分会委员，世界中医药联合会中医疗养专委会理事，上海市中医药学会肾病分会委员，上海市中医药学会补肾活血法分会委员，上海市医师协会中医医师分会委员，浦东新区肾内科专委会委员。主持市、局级科研项目5项，参编著作一部，核心期刊发表论文18篇。

海派陆氏针灸治疗脏腑病经验分享

讲者：金珠；主持：金周惠

金珠

副主任医师
针灸科、推拿科主任
硕士生导师
针推教研室主任
临床业务：海派中医的传承者
国家级非物质文化遗产“陆氏针灸”第四代传承人：3位陆氏导师
上海市名中医（陈跃来）的继承人、传承团队成员
上海高水平地方高校吴焕淦教授领衔的针灸免疫效应与针麻研究创新团队成员
浦东新区学科带头人
七院名中医
第一负责人主持国家级课题1项，市级课题3项，区级课题6项

2023.10.7陆氏针灸治疗脏腑病的经验分享下载

金周慧

上海市浦东新区人民医院中医科主任、主任医师、教授、硕导
上海市中医临床优势学科（肾脏病）学科带头人、上海市非中医类别医师学习中医专家库专家
上海市浦东新区慢性肾脏病品牌倍增项目学科带头人，上海市浦东新区金周慧中医名家工作室导师，上海市浦东新区名中医。
上海市中医医院名老中医诊疗所名专肾病科特聘主任医师
主要社会任职和学术成果
中国中医药研究促进会中医全科医学与养生分会副主任委员、中国民族医药学会肾病分会理事、上海市中医药学会综合医院中医药工作委员会常委，上海市中医药学会肾病分会常委、上海市中医医疗质量控制中心综合医院中医药质控组专家委员会委员、上海市中医药学会围手术期分会委员等职。发表学术论文50余篇，参编专著3部，发明专利3项，实用性专利2项，承担省市级科研课题10余项，获得中华中医药学会科技进步三等奖1次，上海市中西医结合学会科技进步奖2次。
专业特长
从事中医临床工作30年，擅长中医综合治疗急慢性肾小球肾炎，激素依赖性微小病变、膜性肾病、IgA肾病、不明原因血尿、蛋白尿，痛风性肾病、糖尿病肾病、高血压肾病、狼疮性肾炎、急慢性尿路感染、肾囊肿、尿路结石，慢性肾功能衰竭，以及对风湿、类风湿性关节炎、干燥综合征、强直性脊柱炎、带状疱疹、肿瘤术后调理、头痛、眩晕、不寐、咳喘等疾病的治疗。
应用”通调三焦水道治水肿”，“育阴潜阳治消渴”，“开达膜原治肾衰”的中医特色治法在难治性肾病的治疗上具有较好疗效。在减少蛋白尿的流失及血尿的发生，改善自觉症状，减少激素使用过程中的相关副作用，提高生活质量上具有明显效果。
专家门诊时间：周二上午。特需糖尿病肾病专病门诊时间：周五上午。

药物相关性肾损伤

讲者：廖琳；主持：路建饶

廖琳

上海市第七人民医院肾内科副主任医师，医学硕士
硕士生导师，诊疗组组长
主要研究方向为慢性肾纤维化和糖尿病性肾病的临床和实验研究。
承担并参与国家自然科学基金1项、上海市各类基金等科研项目10余项；以第一作者核心期刊发表论文12篇、SCI论文3篇；拥有实用新型专利3项；主编和参编著作6部。
获第十一届东方肾脏病学会议OCN2021 优秀壁报奖、2021年度华夏医学科技奖三等奖1项、上海市中西医结合科学技术奖三等奖2项。
现任上海市中医药学会第十届肾病分会委员、上海市中西医结合学会代谢与免疫肾病专委会委员、上海中西医结合学会肾病专委会委员、上海市浦东新区医学会中医肾病专委会委员、上海市浦东新区医学会肾内科专业委员会青年委员。

药物性肾损伤-廖琳下载

路建饶

上海第七人民医院 肾脏科主任
博士，主任医师，教授，博士生（后）导师
国家中管局“十二五”肾病重点专科学科带头人
中华中医药学会肾脏病分会委员
华东肾脏病协作委员会委员
上海市中西医结合肾脏病学会副主任委员
上海市中医肾脏病学会副主任委员
上海市医学会、医师协会肾脏病分会委员
上海市肾内科质控、血液净化质控专家委员会委员
Blood Purification，中华肾脏病杂志，国际泌尿系统杂志、中国综合临床等多种杂志特约审稿人、编委
完成或承担20余项国家和市局级基金，发表论文160余篇，SCI收录20篇。作为第一作者获得中国人民解放军科学技术进步二等奖、三等奖以及华夏医学科技奖、上海市中西医结合科学技术奖等8项；主编和参编著作6部，获得国家专利5项。
主要研究方向：中西医结合防治肾纤维化和血液净化技术临床应用。

高尿酸血症肾损害研究进展

讲者：高建东；主持：潘阳彬

高建东

上海中医药大学附属曙光医院肾病科主任医师、教授，博士生导师，科主任，肾病研究所副所长
第二批全国优秀中医临床人才，上海中医药大学“学术荣誉体系”特聘教授，曙光名中医。
耶鲁大学医学院肾脏科访问学者，曾获上海市医苑新星、银蛇奖
擅长中医药治疗肾衰、肾炎、IgA肾病、膜性肾病、糖尿病肾病、痛风及痛风性肾病、多囊肾病、尿路结石、肾虚证等
发表论文200篇，包括SCI论文20篇。专利2项，科研获奖9项
指导学生荣获第二届（2019年）“全国中医药优秀博士学位论文”提名论文、2018年“岐黄杯第九届全国中医药博士生优秀论文评选活动一等奖”和国家自然科学青年基金项目

高尿酸肾损伤的研究进展-七院学习班-高建东下载

潘阳彬

复旦大学附属浦东医院肾内科主任、主任医师、医学博士、博士生导师
中国病理生理学会肾脏病分会委员
第十届中华医学会肾脏病分会全国青年委员
华东地区肾脏病协作委员会委员
上海市中西医结合学会血液净化专委会委员
浦东新区医学会中医肾病专委会常委
浦东新区医学会肾脏病专委会委员
美国路易斯威尔大学医学院访问学者
研究方向：肾小球足细胞病，腹膜透析。主持国家自然科学基金面上项目2项、省厅级项目6项，发表论文30余篇，其中SCI论文13篇，参编专著3部

假性电解质和酸碱紊乱

讲者：齐华林；主持：王浩

齐华林

博士，主任医师，硕士研究生导师，肾脏科主任
浦东新区中医肾病副主任委员
上海市中西医结合肾脏病专委会委员、血液净化专委会委员
浦东新区卫生质量控制中心血透质控组长
上海市康复医学会肾脏病分会委员
中国非公医疗肾脏与透析专委会委员
浦东新区卫健委重点学科负责人
擅长水电解质酸碱平衡、慢性肾脏病和腹膜透析管理，重症肾脏病诊治
上海市科委课题2项，浦东新区科委1项，浦东新区卫健委领先人才
发表SCI期刊收录论文6篇，IF>5分2篇，中华系列3篇

齐华林-假性电解质酸碱紊乱识别（七院会议20231008）下载

王浩

上海市普陀区中心医院肾内科主任、主任医师、硕士研究生导师，上海市医学重点专科学科带头人
学术兼职
上海市医学会肾脏病专科分会委员
上海市肾内科临床质控专家委员会委员
上海市医师协会肾病分会委员
上海市医院协会血液净化管理专业委员会
上海市中西医结合学会肾脏病专业委员会委员
上海市中西医结合学会血液净化管理专业委员会委员
上海市康复医学会肾脏康复委员会委员
擅长血液净化及肾脏病的中西医结合治疗。获得中华中医药科技奖、中国中西医结合科技奖等多项奖项。主编专著1部、副主编3部

肿瘤相关肾病诊治新进展

讲者：刘娜；主持：廖林

刘娜

医学博士、二级教授、主任医师、博士生导师、博士后合作导师
全国卫生系统优秀工作者，上海市劳动模范
第七批全国老中医专家学术经验继承工作指导老师、上海市名中医、上海市领军人才
国家临床重点专科、教育部重点学科（肾病）、教育部重点实验室（肾病）、国家中医药管理局肾病重点学科和专科、上海市重点学科（肾病）、上海市教委肾病创新团队带头人
中华中医药学会内科分会副主任委员
世界中医药联合会医案分会副会长
中国民族医药学会肾病分会副会长
中国医药教育协会中医药教育促进工作委员会副主任委员
中国中西医结合学会肾脏专业委员会常委，上海市副主委
上海市中医药学会常务理事
上海市中医药学会肾病分会主任委员
上海市中医肾病临床研究基地、海派名医童少伯研究基地负责人
从事肾病科临床和基础工作30余年，在中西医药防治慢性肾脏疾病的临床诊疗和科学研究方面取得显著的成绩。先后主持国家及上海市重大科研项目18项。以第一或通讯作者发表论文430余篇，其中SCI收录的英文论文38篇，影响因子总和80多分。主编专著8部，参编6部。作为第一完成人获教育部、上海市、中国中西医结合学会、中华中医药学会科技进步、上海市医学会二等奖11项，上海市中西医结合学会、中医学会一等奖各1项，国家知识产权局授权专利8项。

2023-刘娜课件-肿瘤相关性肾病诊治新进展下载

廖林

上海市第七人民医院肾内科副主任医师，医学硕士
硕士生导师，诊疗组组长
主要研究方向为慢性肾纤维化和糖尿病性肾病的临床和实验研究。
承担并参与国家自然科学基金1项、上海市各类基金等科研项目10余项；以第一作者核心期刊发表论文12篇、SCI论文3篇；拥有实用新型专利3项；主编和参编著作6部。
获第十一届东方肾脏病学会议OCN2021 优秀壁报奖、2021年度华夏医学科技奖三等奖1项、上海市中西医结合科学技术奖三等奖2项。
现任上海市中医药学会第十届肾病分会委员、上海市中西医结合学会代谢与免疫肾病专委会委员、上海中西医结合学会肾病专委会委员、上海市浦东新区医学会中医肾病专委会委员、上海市浦东新区医学会肾内科专业委员会青年委员。

慢性肾脏病的常见病因与中西医结合诊疗

讲者：徐震宇；主持：陈杰

徐震宇

副主任医师 硕士研究生导师
上海市第七人民医院急诊内科兼感染性疾病科主任
第二批上海市“杏林新星”
第三批上海市中医近代流派传承继承人
浦东新区中医高级师承人才
浦东新区重点专科（中西医结合急诊内科）负责人
第五届中华中医药学会急危重症分会委员
第九届上海市医学会急诊专委会青年委员
第四届上海市医学会门诊管理委员会委员
第一届上海市中医药学会慢病管理专委会委员
第一届上海市中医药学会创伤康复分会委员
第一届上海市中医药学会补肾活血法分会委员

徐震宇-慢性肾脏病的常见病因和中西医结合诊疗下载

陈杰

副主任医师、硕士生导师
上海市第七人民医院肾病科副主任
中国民族医药协会肾病分会及科普分会理事
上海市中医药学会肾病分会委员
上海市医学会肾脏康复学会常委
上海市浦东新区医学会肾内科专业委员会以及中医肾病专业委员会常委
上海市浦东新区医学会叶景华全国名老中医工作室成员
浦东新区中医继承人，师从上海市名中医叶景华主任、浦东新区名中医叶玉妹主任。
主要研究方向：益肾清利法治疗蛋白尿，健脾活血祛风法治疗糖尿病肾病，扶正解毒泄浊法治疗肾衰等肾脏疾病。
主持市科委课题3项、市局级课题1项、区局级课题1项、市专病建设项目1项，参与国自然等其他课题多项，在核心期刊发表论文38篇，SCI收录6篇，参编肾脏病学术著作3部，获华夏科技奖1项、上海市中西医结合科技奖2项，浦东新区科技术奖1项，获国家发明专利2项，实用新型专利2项。

慢性肾脏病伴高血压的中医药治疗

讲者：胡静；主持：鲍晓荣

胡静

教授、主任医师、硕士生导师
国家中医药管理局“十二五”重点建设专科（肾病） 、上海市肾病优势专科科室科主任
2022首届中国人口文化促进会国医名师学术经验传承工作委员会副会长
上海市中医药学会第十届肾病分会常务委员
世界中联临床用药安全研究专业委员会第二届理事会常务理事
上海市浦东新区医学会中医肾病专业委员会主任委员
中国民族医药学会肾病分会理事
中国非公医疗机构协会肾脏病透析专业委员会第二届委员会委员
上海电视台“X诊所”节目特约中医专家
从事肾病科临床和基础工作30余年，在中西医药防治慢性肾脏疾病的临床诊疗和科学研究方面取得显著的成绩。先后主持和参加上海市以及浦东新区10余项课题研究，主编肾病学科及中医学科专著6部。近5年发表专业论文21篇，其中核心期刊17篇，SCI文章5篇。获得浦东新区科学技术进步、上海中西医结合科学技术三等奖各1项。国家知识产权局授权专利3项。

慢性肾脏病伴高血压的中西医药物治疗下载

鲍晓荣

教授 、医学博士，主任医师，研究生导师
上海市金山区医学会副会长
复旦大学附属金山医院内科教研室主任、内科住院医师规培基地主任、临床技能培训中心主任、肾内科主任
上海市医师学会肾脏内科分会委员
上海市医学会中西医结合肾脏病专委会常务委员
上海市医院管理学会血液透析专委会委员
九三学社上海市委医疗卫生专委会副主任

CKD-MBD的管理

讲者：路建饶；主持：张黎明

路建饶

上海第七人民医院 肾脏科主任
博士，主任医师，教授，博士生（后）导师
国家中管局“十二五”肾病重点专科学科带头人
中华中医药学会肾脏病分会委员
华东肾脏病协作委员会委员
上海市中西医结合肾脏病学会副主任委员
上海市中医肾脏病学会副主任委员
上海市医学会、医师协会肾脏病分会委员
上海市肾内科质控、血液净化质控专家委员会委员
Blood Purification，中华肾脏病杂志，国际泌尿系统杂志、中国综合临床等多种杂志特约审稿人、编委
完成或承担20余项国家和市局级基金，发表论文160余篇，SCI收录20篇。作为第一作者获得中国人民解放军科学技术进步二等奖、三等奖以及华夏医学科技奖、上海市中西医结合科学技术奖等8项；主编和参编著作6部，获得国家专利5项。
主要研究方向：中西医结合防治肾纤维化和血液净化技术临床应用。

CKD-MBD的管理-路建饶下载

张黎明

主任医师
上海市静安区闸北中心医院肾内科主任
上海市医学重点学科负责人
上海市医学会肾脏病专科分会第十二届委员会委员
上海市医师协会肾脏病分会第三届委员会委员
上海市中西医结合学会第一届代谢与免疫肾病专委会 委员
上海市医院协会血液净化专业委员会委员
上海市肾脏康复专业委员会常委
华东六省一市肾脏病协作组委员会委员
上海市中西医结合学会肾病专业委员会委员
上海市中西医结合学会血液净化专业委员会委员
上海市静安区医学会肾脏病学组组长

糖尿病肾病中西医结合治疗进展

讲者：陈杰；主持：张黎明

陈杰

副主任医师、硕士生导师
上海市第七人民医院肾病科副主任
中国民族医药协会肾病分会及科普分会理事
上海市中医药学会肾病分会委员
上海市医学会肾脏康复学会常委
上海市浦东新区医学会肾内科专业委员会以及中医肾病专业委员会常委
上海市浦东新区医学会叶景华全国名老中医工作室成员
浦东新区中医继承人，师从上海市名中医叶景华主任、浦东新区名中医叶玉妹主任。
主要研究方向：益肾清利法治疗蛋白尿，健脾活血祛风法治疗糖尿病肾病，扶正解毒泄浊法治疗肾衰等肾脏疾病。
主持市科委课题3项、市局级课题1项、区局级课题1项、市专病建设项目1项，参与国自然等其他课题多项，在核心期刊发表论文38篇，SCI收录6篇，参编肾脏病学术著作3部，获华夏科技奖1项、上海市中西医结合科技奖2项，浦东新区科技术奖1项，获国家发明专利2项，实用新型专利2项。

糖尿病肾病中西医治疗现况下载

张黎明

主任医师
上海市静安区闸北中心医院肾内科主任
上海市医学重点学科负责人
上海市医学会肾脏病专科分会第十二届委员会委员
上海市医师协会肾脏病分会第三届委员会委员
上海市中西医结合学会第一届代谢与免疫肾病专委会 委员
上海市医院协会血液净化专业委员会委员
上海市肾脏康复专业委员会常委
华东六省一市肾脏病协作组委员会委员
上海市中西医结合学会肾病专业委员会委员
上海市中西医结合学会血液净化专业委员会委员
上海市静安区医学会肾脏病学组组长

何立群教授清化祛瘀法临床学习及应用体会

讲者：盖云；主持：胡静

盖云

中医学博士、主任医师、副教授、硕士研究生导师
全科医疗科/肿瘤一科科主任
擅长中医体质调养、慢性疲劳综合症、慢性肾脏病，中西医结合诊治肿瘤类疾病及肿瘤类疾病的全程健康管理等。
浦东新区中医领军型人才
上海市名老中医经验继承高级研修班学员，师承叶景华、何立群教授；第六批全国名老中医经验继承班学员，师承徐振晔、周永明、凌昌全教授。
现任上海市中西医结合学会副主任委员，上海市亚健康协会专业委员会常务委员，上海市中医药学会慢病管理分会常务委员，中华中医药学会健康管理分会委员。
负责市、区各级科研课题多项，发表论文二十余篇。
主编《跟名医做临床之内科难病》《治未病学》，参编《海上名医医案心悟》 、《叶景华诊治肾病经验》等。

盖云-何立群清化祛瘀法临床学习及应用体会下载

胡静

教授、主任医师、硕士生导师
国家中医药管理局“十二五”重点建设专科（肾病） 、上海市肾病优势专科科室科主任
2022首届中国人口文化促进会国医名师学术经验传承工作委员会副会长
上海市中医药学会第十届肾病分会常务委员
世界中联临床用药安全研究专业委员会第二届理事会常务理事
上海市浦东新区医学会中医肾病专业委员会主任委员
中国民族医药学会肾病分会理事
中国非公医疗机构协会肾脏病透析专业委员会第二届委员会委员
上海电视台“X诊所”节目特约中医专家
从事肾病科临床和基础工作30余年，在中西医药防治慢性肾脏疾病的临床诊疗和科学研究方面取得显著的成绩。先后主持和参加上海市以及浦东新区10余项课题研究，主编肾病学科及中医学科专著6部。近5年发表专业论文21篇，其中核心期刊17篇，SCI文章5篇。获得浦东新区科学技术进步、上海中西医结合科学技术三等奖各1项。国家知识产权局授权专利3项。

慢性尿路感染中医药诊治优势

讲者：杨晓萍；主持：陈杰

杨晓萍

中医内科博士、副教授、硕士生导师、全科教研室主任、全科（肿瘤一科）副主任
担任上海市中医药学会中医临床经典分会委员
上海市中医药学会青年学术研究分会委员
上海市中医药学会脑病分会委员
上海市中医药学会神志病分会委员
上海市中医药学会肾病分会委员
中国肾内科医师协会会员
中国中医药信息学会全科分会理事
以第一课题负责人完成浦东新区卫计委、浦东新区科协、上海市中发办课题共3项，各类人才培养3项
第一作者发表论文20余篇，参编中医肾病专著及中医科普专著共2本
2013年获得上海市职工创新奖提名奖，2014年申报并举办中管局国家继续教育班一次

杨晓萍-尿路感染的中西医治疗下载

陈杰

副主任医师、硕士生导师
上海市第七人民医院肾病科副主任
中国民族医药协会肾病分会及科普分会理事
上海市中医药学会肾病分会委员
上海市医学会肾脏康复学会常委
上海市浦东新区医学会肾内科专业委员会以及中医肾病专业委员会常委
上海市浦东新区医学会叶景华全国名老中医工作室成员
浦东新区中医继承人，师从上海市名中医叶景华主任、浦东新区名中医叶玉妹主任。
主要研究方向：益肾清利法治疗蛋白尿，健脾活血祛风法治疗糖尿病肾病，扶正解毒泄浊法治疗肾衰等肾脏疾病。
主持市科委课题3项、市局级课题1项、区局级课题1项、市专病建设项目1项，参与国自然等其他课题多项，在核心期刊发表论文38篇，SCI收录6篇，参编肾脏病学术著作3部，获华夏科技奖1项、上海市中西医结合科技奖2项，浦东新区科技术奖1项，获国家发明专利2项，实用新型专利2项。

活血化瘀通络法治疗早中期慢性肾衰临床与实验研究进展

讲者：张长明；主持：陈杰

张长明

主任医师，医学博士，硕士生导师
中华中医药学会肾病分会委员
上海中医药学会肾病分会副主任委员
浦东新区中医肾病专委会副主任委员
世界中医药联合会医案专业委员会理事。
从事临床工作30年，擅长治疗慢性肾炎、慢性肾衰、难治性肾病综合征、复发性尿路感染、代谢性肾损伤及肾虚证的中医调理。长期从事慢性肾衰和慢性尿路感染的临床和科研工作，近几年来，完成卫健委中医辨证论治慢性复发性尿路感染中医特色诊疗项目；作为海派中医丁氏内科浦东基地负责人，在中医络病理论指导下，研究抗纤灵颗粒活血化瘀通络法治疗早中期慢性肾衰。

活血化瘀通络法治疗早中期慢性肾衰临床与实验研究进展——张长明下载

陈杰

副主任医师、硕士生导师
上海市第七人民医院肾病科副主任
中国民族医药协会肾病分会及科普分会理事
上海市中医药学会肾病分会委员
上海市医学会肾脏康复学会常委
上海市浦东新区医学会肾内科专业委员会以及中医肾病专业委员会常委
上海市浦东新区医学会叶景华全国名老中医工作室成员
浦东新区中医继承人，师从上海市名中医叶景华主任、浦东新区名中医叶玉妹主任。
主要研究方向：益肾清利法治疗蛋白尿，健脾活血祛风法治疗糖尿病肾病，扶正解毒泄浊法治疗肾衰等肾脏疾病。
主持市科委课题3项、市局级课题1项、区局级课题1项、市专病建设项目1项，参与国自然等其他课题多项，在核心期刊发表论文38篇，SCI收录6篇，参编肾脏病学术著作3部，获华夏科技奖1项、上海市中西医结合科技奖2项，浦东新区科技术奖1项，获国家发明专利2项，实用新型专利2项。

护肾战“狼”记——B细胞靶向生物制剂治疗狼疮性肾炎病例分享

讲者：张传富；主持：路建饶

张传富

副主任医师 硕士研究生 硕士生导师
上海市第七人民医院 风湿免疫科主任
叶景华全国名老中医传承工作室传承人
上海市中医学会风湿病分会委员
上海市中西医结合学会风湿病分会委员
上海市医师协会风湿免疫科分会第三届委员会委员

护肾战狼记-B细胞靶向生物制剂治疗LN病例分享10.6下载

路建饶

上海第七人民医院 肾脏科主任
博士，主任医师，教授，博士生（后）导师
国家中管局“十二五”肾病重点专科学科带头人
中华中医药学会肾脏病分会委员
华东肾脏病协作委员会委员
上海市中西医结合肾脏病学会副主任委员
上海市中医肾脏病学会副主任委员
上海市医学会、医师协会肾脏病分会委员
上海市肾内科质控、血液净化质控专家委员会委员
Blood Purification，中华肾脏病杂志，国际泌尿系统杂志、中国综合临床等多种杂志特约审稿人、编委
完成或承担20余项国家和市局级基金，发表论文160余篇，SCI收录20篇。作为第一作者获得中国人民解放军科学技术进步二等奖、三等奖以及华夏医学科技奖、上海市中西医结合科学技术奖等8项；主编和参编著作6部，获得国家专利5项。
主要研究方向：中西医结合防治肾纤维化和血液净化技术临床应用。

如何降低长期深静脉置管的感染率

讲者：陈静；主持：黄黎静

陈静

上海长征医院血液净化中心护士长
中华护理学会血液净化专委会委员
上海市护理学会血液净化专委会主任委员
上海市血液净化质量控制中心督查专家
从事血液净化护理工作三十余年
荣获49届南丁格尔奖章

慢性肾脏病高血钾的预防与综合管理策略下载