肾病综合征肾病综合征Nephrotic SyndromeNephrotic Syndrome

武汉大学第一临床学院 刘红燕武汉大学第一临床学院 刘红燕

DefinitionDefinition

Nephrotic syndrome (NS) is defined Nephrotic syndrome (NS) is defined by the presence of following:by the presence of following:

Heavy proteinuria (>3.5g/d)Heavy proteinuria (>3.5g/d) Hypoalbuminemia (serum albumin Hypoalbuminemia (serum albumin

<30g/L)<30g/L) Peripheral edemaPeripheral edema Hyperlipidemia / Hyperlipidemia /

hypercholesterolemiahypercholesterolemia

Major causes of NS Major causes of NS (primary or idiopathic)(primary or idiopathic)

Minimal change disease (Minimal change disease ( 微小病变型）微小病变型）

Mesangial proliferative glomerulonephritis Mesangial proliferative glomerulonephritis （系膜增生性肾小球肾炎）（系膜增生性肾小球肾炎）

Focal segmental glomerulonephritis Focal segmental glomerulonephritis （局灶节段（局灶节段硬化性肾小球肾炎）硬化性肾小球肾炎）

Membranous glomerulonephritis Membranous glomerulonephritis （膜性肾病）（膜性肾病）

Membranoproliferative glomerulonephritis Membranoproliferative glomerulonephritis （膜增殖性肾小球肾炎（膜增殖性肾小球肾炎 // 系膜毛细血管性肾小球肾炎）系膜毛细血管性肾小球肾炎）

Major causes of NS Major causes of NS (secondary or systemic)(secondary or systemic)

Antoimmune: systemic lupus erythematosus Antoimmune: systemic lupus erythematosus (SLE)(SLE)

Endocrine: diabetic nephropathyEndocrine: diabetic nephropathy

Infections: Hepatitis B, C, HIVInfections: Hepatitis B, C, HIV

Allergenic: Henoch-Schonlen purpuraAllergenic: Henoch-Schonlen purpura

Neoplastic: Hodgkin’s and non-Hodgkin’s Neoplastic: Hodgkin’s and non-Hodgkin’s lymphomas, multiple myelomalymphomas, multiple myeloma

Others: Amyloidosis, Hereditary nephritis, Others: Amyloidosis, Hereditary nephritis, medicationsmedications

PathophysiologyPathophysiology

Heavy protinuriaHeavy protinuria HypoalbuminemiaHypoalbuminemia EdemaEdema HyperlipidemiaHyperlipidemia

Heavy proteinuriaHeavy proteinuria Damage to the charge-selective Damage to the charge-selective

barrier of GMB →ultrafiltration of barrier of GMB →ultrafiltration of negatively charged albuminnegatively charged albumin

Damage to the size-selective Damage to the size-selective barrier of GMB →passsage of lager barrier of GMB →passsage of lager molecular proteinsmolecular proteins

Protein filtration > reabsorption Protein filtration > reabsorption capacity of tubulescapacity of tubules

Heperperfusion/Hyperfiltration Heperperfusion/Hyperfiltration factors (hypertension, protein-factors (hypertension, protein-rich diet) →proteinuria increaserich diet) →proteinuria increase

Consequence of Consequence of urinary loss of plasma urinary loss of plasma

proteinsproteins Serum protein ↓or Serum protein ↓or hypoalbuminemiahypoalbuminemia

IgG/Complement ↓→infectionIgG/Complement ↓→infection Coagulation component Coagulation component

alternation (anticoagulants alternation (anticoagulants ↓)→thrombosis↓)→thrombosis

Hormone-binding proteins Hormone-binding proteins ↓/metal-binding proteins ↓/metal-binding proteins ↓→endocrine or metabolic ↓→endocrine or metabolic abnormalitiesabnormalities

Lager proteins may increaseLager proteins may increase

HypoalbuminemiaHypoalbuminemia

Urinary lossUrinary loss albumin catabolism ↑ by albumin catabolism ↑ by

tubulestubules Malnutrition due to GI Malnutrition due to GI

changeschanges

Edema Edema Reduced plasma oncotic pressure Reduced plasma oncotic pressure

(colloid osmotic pressure)(colloid osmotic pressure)

Hypovolemia →renin-angiotensin-Hypovolemia →renin-angiotensin-aldosteron ↑ ; Sympathetic aldosteron ↑ ; Sympathetic nervouse and vasopression nervouse and vasopression systems ↑systems ↑

Primary renal NaPrimary renal Na++ retension (non- retension (non-plasma Hormone effects on the plasma Hormone effects on the kidney)kidney)

Hyperlipidemia Hyperlipidemia One of the sentinel features of One of the sentinel features of

NS with numerous alterations NS with numerous alterations in lipids profiles in lipids profiles (hypercholesterolemia, (hypercholesterolemia, hypertriglyceridemia, LDL and hypertriglyceridemia, LDL and VLDL ↑)VLDL ↑)

Overproduction by the liver of Overproduction by the liver of lipoproteinslipoproteins

Decreased catabolism of Decreased catabolism of lipoproteins and triglyceridelipoproteins and triglyceride

Minimal changes Minimal changes nephropathynephropathy

(MCD, (MCD, 微小病变型肾病）微小病变型肾病）Overview and TerminologyOverview and Terminology

First described in 1913 by First described in 1913 by Monk as “lipoid nephrosis”Monk as “lipoid nephrosis”

other terms “nil disease” other terms “nil disease” and “idiopathic nephrotic and “idiopathic nephrotic syndrome”syndrome”

Pathogenesis Pathogenesis

UnclearUnclear Most likely a consequence Most likely a consequence

of T cell abnormalities of T cell abnormalities (glomerular permembility (glomerular permembility factor)factor)

Other potential Other potential mechanisms (circulating mechanisms (circulating immune complexes)immune complexes)

HistopathologyHistopathology

Light microscope (LM)Light microscope (LM) Lack alteration in glomerular Lack alteration in glomerular

structurestructure Some lipid droplets in tubule cellsSome lipid droplets in tubule cells

Immunoflurescent microscopy( IM)Immunoflurescent microscopy( IM) No changeNo change

Electron microscopy (EM)Electron microscopy (EM) Fusion of epithelial foot processesFusion of epithelial foot processes

Clinical presentationClinical presentation Most common in children; Most common in children;

accouting for 10%-15% of NS accouting for 10%-15% of NS in adults with male in adults with male predominancepredominance

Typical feature of NSTypical feature of NS Uncommon with nephritic Uncommon with nephritic

features (hematuria, features (hematuria, hypertension)hypertension)

Renal function (normal or Renal function (normal or dereasesd transiterily)dereasesd transiterily)

Diagonosis Diagonosis Children and prealdolescent Children and prealdolescent

children presenting with NS children presenting with NS will have MCD (about 80%-will have MCD (about 80%-85%)85%)

Children with NS sensitive to Children with NS sensitive to steroid treatmentsteroid treatment

Secondary MCD kept in mind Secondary MCD kept in mind when adult or old patients when adult or old patients presents with MCDpresents with MCD

Renal biopsyRenal biopsy

Treatment (1)Treatment (1)

Corticosteroid therapyCorticosteroid therapy Exquisitely sensitiveExquisitely sensitive Dose of prednisoneDose of prednisone Caution with the side-Caution with the side-

effects of steroid effects of steroid

Dose of prednisoneDose of prednisone

ChildrenChildren 2mg/kg/2mg/kg/

d<60mg/d×8-d<60mg/d×8-12w 12w

10%reduction/10%reduction/1-2w1-2w

Effetively Effetively minimal minimal dose(10mg/d)×dose(10mg/d)×6-12m6-12m

InitialInitial

(full)(full)

TaperingTapering(slowly)(slowly)

MaintaineceMaintainece

(longer)(longer)

AdultAdult 1 mg/kg/d×8-12w1 mg/kg/d×8-12w

10%reduction/1-10%reduction/1-2w2w

Effetively Effetively minimal minimal dose(10mg/d)×6-dose(10mg/d)×6-12m12m

Treatment (2)Treatment (2)

Cytotoxic therapyCytotoxic therapy For patients with more relapses, For patients with more relapses,

steroid-dependant or steroid-steroid-dependant or steroid-resistantresistant

CyclophosphamideCyclophosphamide

2mg.kg2mg.kg-1-1.d.d-1-1; total dose 6-8g; ; total dose 6-8g; side-effectsside-effects

Chlorambucil Chlorambucil (( 苯丁酸氮芥）苯丁酸氮芥） 0.1-0.2mg/kg/d for 8 weeks0.1-0.2mg/kg/d for 8 weeks

Treatment(3)Treatment(3)

CyclosporineCyclosporine Selectively inhibits Th, TcSelectively inhibits Th, Tc As the second line medication to treat As the second line medication to treat

patients with steroid-resistant, patients with steroid-resistant, frequently relapsing/steroid-dependent frequently relapsing/steroid-dependent MCDMCD

5 mg .kg5 mg .kg-1-1.d.d-1-1 for 8-12 weeks, then for 8-12 weeks, then tapering tapering

Side effectsSide effects

Treatment (4)Treatment (4)

Other medications: MMFOther medications: MMF General therapyGeneral therapy Symptomatic treatmentSymptomatic treatment Chinese medicineChinese medicine

Mesangial proliferative Mesangial proliferative glomerulonephritisglomerulonephritis

(MsPGN, (MsPGN, 系膜增生性肾小球肾炎）系膜增生性肾小球肾炎）

Overview and Overview and TerminologyTerminology

MsPGN is a morphlogic entity and MsPGN is a morphlogic entity and characterized by glomerular characterized by glomerular mesangial hypercellularitymesangial hypercellularity

This morphologic definition includes This morphologic definition includes many well-characterized GNs (IgA many well-characterized GNs (IgA nephropathy, Henoch-Schonlein nephropathy, Henoch-Schonlein purpura nephritis, lupus nephritis purpura nephritis, lupus nephritis and others)and others)

When these well-defined entities are When these well-defined entities are diagnosed and excluded, the diagnosed and excluded, the resuliting are known as MsPGN or resuliting are known as MsPGN or non-IgA MsPGNnon-IgA MsPGN

Pathogenesis Pathogenesis

UnclearUnclear Possibly due to immune Possibly due to immune

complex depositon and complex depositon and complement fixationcomplement fixation

Altered mesangial Altered mesangial function may play an function may play an active roleactive role

Clinic presentationClinic presentation More in adolescents and young More in adolescents and young

adults, more male patientsadults, more male patients 50% of patients with a pre-50% of patients with a pre-

episode of upper respiratory tract episode of upper respiratory tract infectioninfection

70% of patients with hematuria70% of patients with hematuria Some patients with mild Some patients with mild

hypertension, azotemiahypertension, azotemia Accounting for 20-25% of renal Accounting for 20-25% of renal

biopsed patients and 30% of biopsed patients and 30% of primary NSprimary NS

Histopathology Histopathology LMLM Varying degrees of mesangial Varying degrees of mesangial

hypercellularity with an increase hypercellularity with an increase in mesangial matrixin mesangial matrix

IMIM

IgG, IgM, CIgG, IgM, C33 deposition in deposition in

mesangial region and/or in mesangial region and/or in capillary wall in granular patterncapillary wall in granular pattern

EMEM Elctron-dense deposits in the Elctron-dense deposits in the

mesangiummesangium

Differential diagnosisDifferential diagnosis

Clinical presentationClinical presentation Renal biopsyRenal biopsy Exclusion of the Exclusion of the

secondary GN and other secondary GN and other primary glomerulopathies primary glomerulopathies (IgA nephropathy)(IgA nephropathy)

Treatment Treatment

Therapy for MsPGN not-Therapy for MsPGN not-defined defined

Efficacy of steroid or Efficacy of steroid or cytotoxic therapy depends cytotoxic therapy depends on the degree of pathologic on the degree of pathologic injuryinjury

Other medications (ACEI Other medications (ACEI /ARB /Chinese medicine)/ARB /Chinese medicine)

Membranous Membranous NephropathyNephropathy

(MN, (MN, 膜性肾病）膜性肾病）Overview and TerminologyOverview and Terminology

Most common pattern of Most common pattern of idiopathic NS in adults, less idiopathic NS in adults, less common than MCD in childrencommon than MCD in children

15-25% of MN adult patients 15-25% of MN adult patients with no associated systemic with no associated systemic illnessesillnesses

Up to 30% of MN patients with Up to 30% of MN patients with associated systemic associated systemic illnesses(SLE,HBV,tumors)illnesses(SLE,HBV,tumors)

PathogenesisPathogenesis

Immune complex Immune complex formation in situ at the formation in situ at the subepithelial capillary subepithelial capillary wallwall

Deposition of circulating Deposition of circulating immune complexes immune complexes

Complement activation Complement activation →proteinuria→proteinuria

Clinical presentationClinical presentation Heavy proteinuria in more than 80% Heavy proteinuria in more than 80%

of patients with full expression of NSof patients with full expression of NS 30% of patients with microscopic 30% of patients with microscopic

hematuriahematuria More male patients and more severeMore male patients and more severe 80%-90% of patients old than 30 80%-90% of patients old than 30

years at diagnosis years at diagnosis The older the patients, the greater The older the patients, the greater

possibility of malignancypossibility of malignancy Most common pattern of NS Most common pattern of NS

associated with venous thrombosesassociated with venous thromboses

HistopathologyHistopathology

Usually classified as four stagesUsually classified as four stages

LMLM: capillary walls thickened with : capillary walls thickened with subepithelial projections (Spikes) subepithelial projections (Spikes)

IMIM: strong granular capillary wall : strong granular capillary wall staining for IgG, C staining for IgG, C33

EMEM: subepithelial electron-dense : subepithelial electron-dense deposits all along the capillary walls deposits all along the capillary walls

Diagnosis(1)Diagnosis(1)

Based on histological Based on histological findings in patients whose findings in patients whose history, physical history, physical examination and examination and appropriated laboratory appropriated laboratory tests exclue the likelihood tests exclue the likelihood of a secondary causeof a secondary cause

Diagnosis(2)Diagnosis(2)

Following lab tests negtive or Following lab tests negtive or normalnormal

Antinuclear AbAntinuclear Ab Anti-DNA AbAnti-DNA Ab Rheumatoid factorRheumatoid factor Glycosylated HBGlycosylated HB Hepatitis Ag or AbHepatitis Ag or Ab Carcinoembryonic AgCarcinoembryonic Ag cryoglobulinscryoglobulins

Treatment (1)Treatment (1)

Treatment of idiopathic Treatment of idiopathic MN remains controversial MN remains controversial and should be and should be individualizedindividualized

Steroids+Cytotoxic Steroids+Cytotoxic (ponticelli protocol)(ponticelli protocol)

Ponticelli protocolPonticelli protocol Months 1, 3, Months 1, 3,

5 5 methylprednimethylprednisone 1.0 iv sone 1.0 iv qd×3dqd×3d

Months 2, Months 2, 4, 6 4, 6 chlorambucchlorambucil il 0.2mg/kg/d0.2mg/kg/d then then

methylprednisomethylprednisone ne 0.4mg/kg/d×27d0.4mg/kg/d×27d

Treatment (2)Treatment (2)

Immune inhibition Immune inhibition agents(MMF,agents(MMF, 骁悉）骁悉）

ACEI/ARBACEI/ARB Other therapies Other therapies

(anticoagulation)(anticoagulation)

Focal segmental Focal segmental glomerulosclerosisglomerulosclerosis

(FSGS, (FSGS, 局灶节段性肾小球硬化）局灶节段性肾小球硬化）

Terminology Terminology

Focal vs diffuseFocal vs diffuse Some glomeruli involved (focal)Some glomeruli involved (focal) All glomoruli involved (diffuse)All glomoruli involved (diffuse)

Segmental vs global (dealing with Segmental vs global (dealing with individual glomerulus)individual glomerulus)

Only part of the glomerulus Only part of the glomerulus involved (segmental)involved (segmental)

Whole golmerulus involved (global)Whole golmerulus involved (global)

Overview Overview

Accounting for less than Accounting for less than 15% of cases of idiopathic 15% of cases of idiopathic NS in children, but more NS in children, but more in adultsin adults

Hematuria,hypertension Hematuria,hypertension and GFR↓often found in and GFR↓often found in patients at presentationpatients at presentation

Pathogenesis Pathogenesis

Loss of renal Loss of renal mass( compensatory mass( compensatory theory)theory)

GEC injuryGEC injury RAS activationRAS activation Cytokine Cytokine

overproduction(TGF-βoverproduction(TGF-β ））

Clinical presentaionClinical presentaion

Most patients with idiopathic Most patients with idiopathic FSGS present with FSGS present with asymptomatic proteinuria or asymptomatic proteinuria or full NSfull NS

Detection of asympotomatic Detection of asympotomatic cases occurs often at cases occurs often at physicalsphysicals

Patients with NS present Patients with NS present with edemawith edema

HistopathologyHistopathology LM: focal segmental LM: focal segmental

distribution of sclerosis distribution of sclerosis (mesangial matrix ↑,capillary (mesangial matrix ↑,capillary lumen obliteration, adhesion lumen obliteration, adhesion to Bowman’s capsule)to Bowman’s capsule)

IM: IgM and CIM: IgM and C33 deposition in deposition in focal areas(focal areas( 团块状沉积）团块状沉积）

EM: some or extensive EM: some or extensive effacement of foot processeffacement of foot process

Diagnosis Diagnosis Renal biopsy requiredRenal biopsy required Few glomerular sampling may Few glomerular sampling may

not find the sclerotic glomerulusnot find the sclerotic glomerulus Finding of tubular fibrosis in Finding of tubular fibrosis in

such biopsy may suggest the such biopsy may suggest the possibility of unobserved possibility of unobserved sclerosis glomerulisclerosis glomeruli

Patients thought to have MCD Patients thought to have MCD with a poor response to steroids with a poor response to steroids or cytotoxic may have FSGSor cytotoxic may have FSGS

Treatment Treatment

FSGS with normal renal FSGS with normal renal functionfunction

More intensive and more More intensive and more prolonged immunosuppressive prolonged immunosuppressive therapy(6-12months, steroid, therapy(6-12months, steroid, cytotoxic, cyclosporine, MMF)cytotoxic, cyclosporine, MMF)

ACEI/ARBACEI/ARB

FSGS with GFR decreaseFSGS with GFR decrease Follow the therapies for Follow the therapies for

chronic renal failurechronic renal failure

Membranoproliferative Membranoproliferative glomerulonephritisglomerulonephritis

（（ MPGNMPGN ，膜增殖性肾小球肾炎），膜增殖性肾小球肾炎）

Overview and Overview and TerminologyTerminology

Other terms as Other terms as “mesangiocapillary GN(“mesangiocapillary GN( 系膜毛细血系膜毛细血管性肾小球肾炎）”“管性肾小球肾炎）”“ Lobular GN(Lobular GN( 分分叶性肾小球肾叶性肾小球肾炎）”“炎）”“ Hypocmplementemic GNHypocmplementemic GN(( 低补体性肾炎）”低补体性肾炎）”

Secondary conditions are more Secondary conditions are more common than the idiopathic common than the idiopathic formsforms

Pathogenesis Pathogenesis

Immune complex deposition in Immune complex deposition in the mesangial and capillary the mesangial and capillary wall →C activation(for MPGN wall →C activation(for MPGN type Ⅰtype Ⅰ ））

MPGN type Ⅱdoes not appear MPGN type Ⅱdoes not appear to involve immune complex, to involve immune complex, but rather utilize some other but rather utilize some other mechanism for C activationmechanism for C activation

Clinical presentationClinical presentation Less common entity of NS, but if it Less common entity of NS, but if it

occurs, most in children and young occurs, most in children and young adultsadults

Patients present with Nephrotic Patients present with Nephrotic (type Ⅰ, 2/3 slow progression), (type Ⅰ, 2/3 slow progression), Nephritic(type Ⅱ, 5%, aggressive) Nephritic(type Ⅱ, 5%, aggressive) or in combination featuresor in combination features

Preceding upper respiratory Preceding upper respiratory infection and persistent infection and persistent proteinuria, hematuria, proteinuria, hematuria, hypocomplementemic, anemia hypocomplementemic, anemia indicate an incidence of MPGN indicate an incidence of MPGN

HistopathologyHistopathology

LM: marked mesangial LM: marked mesangial proliferation and thickening of proliferation and thickening of GBM, glomrular lobularity, GBM, glomrular lobularity, double contours(tram-tracks)double contours(tram-tracks)

IM: IgG and CIM: IgG and C33 granular deposits granular deposits in mesangium and capillary wallsin mesangium and capillary walls

EM: subendothelial and EM: subendothelial and mesangial electron-dense mesangial electron-dense depositsdeposits

Diagnosis Diagnosis

Clinical featuresClinical features Persistent Persistent

hypocomplementemia, anemia hypocomplementemia, anemia not compatible with renal not compatible with renal damage, nephrotic with damage, nephrotic with hemoturia, early hypertension hemoturia, early hypertension and GFR↓and GFR↓

Renal biopsy with exclusion of Renal biopsy with exclusion of secondary MPGNsecondary MPGN

Treatment and Treatment and prognosisprognosis

Effective therapy neededEffective therapy needed Steroid and cytotoxic maybe Steroid and cytotoxic maybe

effective on some younger age effective on some younger age patientspatients

Symptomatic Symptomatic therapies( anticoagulation)therapies( anticoagulation)

Renal function protecting therapiesRenal function protecting therapies Poor prognosis, 50%of patients Poor prognosis, 50%of patients

following 10 year course progress following 10 year course progress to ESRDto ESRD

小 结小 结 肾病综合征诊断标准肾病综合征诊断标准 尿蛋白尿蛋白 >3.5g/d>3.5g/d 血浆白蛋白低于血浆白蛋白低于 30g/L30g/L 水肿水肿 血脂升高血脂升高 1,21,2 为诊断为诊断 NSNS 所必需所必需

肾综分类和常见病因肾综分类和常见病因

原发性原发性 微小病变性肾病（微小病变性肾病（ MCDMCD ）） 系膜增生性肾小球肾炎（系膜增生性肾小球肾炎（ MsPGNMsPGN ）） 膜性肾病（膜性肾病（ MNMN ）） 局灶节段性肾小球硬化（局灶节段性肾小球硬化（ FSGSFSGS ）） 膜增生性肾小球肾炎（膜增生性肾小球肾炎（ MPGNMPGN ））

继发性继发性 过敏性紫癜性肾炎过敏性紫癜性肾炎 系统性红斑狼疮性肾炎系统性红斑狼疮性肾炎 糖尿病肾病糖尿病肾病 乙肝相关性肾炎乙肝相关性肾炎 肾淀粉样变性肾淀粉样变性 骨髓瘤性肾病骨髓瘤性肾病

病理生理病理生理 大量蛋白尿：电荷屏障、分子屏障受大量蛋白尿：电荷屏障、分子屏障受

损损 血浆蛋白低：尿中丢失、肾小管代谢血浆蛋白低：尿中丢失、肾小管代谢

↑、营养不良↑、营养不良 水肿：血浆胶体渗透压↓、低血容量水肿：血浆胶体渗透压↓、低血容量

→→ RASRAS 活力↑、继发性水钠潴留活力↑、继发性水钠潴留 高脂血症：肝脏合成↑，脂蛋白分解高脂血症：肝脏合成↑，脂蛋白分解

和利用↓和利用↓

微小病变型肾病微小病变型肾病 临床特点：临床特点：儿童多见，成人发病儿童多见，成人发病

低，典型肾综低，典型肾综 病理特点：病理特点： LMLM 正常，正常， IMIM

（－），（－）， EMEM 见足突广泛融合见足突广泛融合 治疗及预后：治疗及预后： 90%90% 病例对糖皮病例对糖皮

质激素敏感，但复发率高达质激素敏感，但复发率高达 60%60%

系膜增生性肾小球肾炎系膜增生性肾小球肾炎 临床特点：临床特点：发病率高，占肾病综合征发病率高，占肾病综合征

50%50% ，好发于青少年，前驱感染史，，好发于青少年，前驱感染史，可并血尿可并血尿

病理特点：病理特点： LM LM 系膜及基质增系膜及基质增生，生， IMIM 系膜区系膜区 IgGIgG ，， IgMIgM ，， CC33颗粒样沉积，颗粒样沉积， EMEM 系膜区电子致密物系膜区电子致密物

治疗及预后：治疗及预后：激素及细胞毒药物治疗激素及细胞毒药物治疗反应与病理轻重有关反应与病理轻重有关

膜性肾病膜性肾病

临床特点：临床特点：好发于中老年人，隐匿起病，极易发好发于中老年人，隐匿起病，极易发生血栓形成，排除继发性原因生血栓形成，排除继发性原因

病理特点：病理特点： LM LM 上皮下钉突形成，上皮下钉突形成， GBMGBM 增增厚厚 ; IM IgG; IM IgG ，， CC33 呈颗粒样沉积呈颗粒样沉积 ; EM GBM; EM GBM上皮侧电子致密物，足突融合上皮侧电子致密物，足突融合

治疗及预后：治疗及预后：早期可由激素和细胞毒药物治疗缓早期可由激素和细胞毒药物治疗缓解 解 (ponticelli(ponticelli 方案方案 ); ); 病变缓慢进展，约病变缓慢进展，约 20-20-35%35% 患者临床表现可自行缓解患者临床表现可自行缓解

局灶节段性肾小球硬化局灶节段性肾小球硬化 临床特点：临床特点：好发于青少年男性、常伴有好发于青少年男性、常伴有

血尿、高血压、血尿、高血压、 GFR↓GFR↓

病理特点：病理特点： LM LM 局灶节段硬化；局灶节段硬化； IM IM IgM IgM ，， CC33 呈团块状沉积，呈团块状沉积， EM EM 足细足细胞足突广泛融合胞足突广泛融合

治疗及预后：治疗及预后：对激素及细胞毒药物反应对激素及细胞毒药物反应差，逐渐发展成肾衰差，逐渐发展成肾衰

膜增生性肾小球肾炎膜增生性肾小球肾炎 临床特点：好发于青少年，常伴血尿，高临床特点：好发于青少年，常伴血尿，高

血压，与肾损害不相称的贫血，低补体血症血压，与肾损害不相称的贫血，低补体血症

病理特点：病理特点： LM LM 系膜及基质弥漫增生，系膜及基质弥漫增生，系膜插入现象，双轨征；系膜插入现象，双轨征； IM IgGIM IgG ，， CC33颗粒样系膜区及毛细血管壁沉积；颗粒样系膜区及毛细血管壁沉积； EM EM 系膜区内皮下电子致密物沉积系膜区内皮下电子致密物沉积

治疗及预后：治疗及预后：治疗困难，对症治疗，保护肾治疗困难，对症治疗，保护肾功能，病变进展快，预后差功能，病变进展快，预后差

肾综常见并发症肾综常见并发症 感染：感染：由于营养不良，免疫功能紊由于营养不良，免疫功能紊乱，应用激素乱，应用激素

血栓和栓塞：血栓和栓塞：由于血液浓缩、高脂由于血液浓缩、高脂血症、抗凝和纤溶系统失衡血症、抗凝和纤溶系统失衡

急性肾衰竭：急性肾衰竭：由于血容量不足或肾由于血容量不足或肾间质水肿压迫肾小管→肾小管阻塞间质水肿压迫肾小管→肾小管阻塞

蛋白质及脂肪代谢紊乱蛋白质及脂肪代谢紊乱

诊断诊断确诊确诊 NSNS 病因诊断、除外继发和遗传性疾病因诊断、除外继发和遗传性疾

病病判断有无并发症判断有无并发症

鉴别诊断鉴别诊断

常见继发性肾综原因常见继发性肾综原因

紫癜性肾损害：紫癜性肾损害：青少年，典型皮疹，腹青少年，典型皮疹，腹痛和关节痛，血尿蛋白尿在皮疹后痛和关节痛，血尿蛋白尿在皮疹后

狼疮性肾炎：狼疮性肾炎：女性多发，多系统受累，女性多发，多系统受累，自身抗体（＋）自身抗体（＋）

DNDN ：：糖尿病史，眼底病变糖尿病史，眼底病变

肾淀粉样变性：肾淀粉样变性：好发于中老年，其它好发于中老年，其它器官受累（心、神经、消化），肾活器官受累（心、神经、消化），肾活检检

骨髓瘤肾病：骨髓瘤肾病：中老年男性多见，骨痛，中老年男性多见，骨痛，血清单克隆球蛋白↑，尿蛋白电泳血清单克隆球蛋白↑，尿蛋白电泳 MM带，尿本周氏蛋白阳性带，尿本周氏蛋白阳性

其它肿瘤性疾病其它肿瘤性疾病

治 疗治 疗 一般治疗原则一般治疗原则 一般治疗一般治疗 利尿消肿利尿消肿免疫抑制治疗免疫抑制治疗调脂治疗调脂治疗抗凝治疗抗凝治疗各种病理类型原发性肾病综合征的各种病理类型原发性肾病综合征的

治疗治疗

治疗治疗 糖皮质激素糖皮质激素 细胞毒药物细胞毒药物 CTXCTX MMFMMF CsACsA 、、 FK506FK506来氟米特（爱诺华） 来氟米特（爱诺华） 中药：雷公藤中药：雷公藤

QuestionsQuestions

This 5-year-This 5-year-old boy has 4+ old boy has 4+ protein in his protein in his urine on stick urine on stick testing. His testing. His serum serum albumin is albumin is 21g/L. What is 21g/L. What is the most likely the most likely diagnosis?diagnosis?

These picture These picture are from the are from the renal biopsy of renal biopsy of a 60-year-old a 60-year-old man who man who presented presented with nephrotic with nephrotic syndrome. syndrome. What is the What is the diagnosis?diagnosis?

How to treat minimal How to treat minimal change disease patients change disease patients with steroid?with steroid?

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