common glomerular disease

Common Glomerular Diseases8 May 2021

Kullaya Takkavatakarn MD.

Division of Nephrology, Department of Medicine,

Faculty of Medicine, Chulalongkorn University

Disclosure

• Berlin Pharmaceutical

• Mainly for MCQ Examination

What should you know about glomerular disease?

• Is it glomerular disease?

• What is the glomerular syndrome?

• What are the possible etiologies?

• What are the proper investigations?

• Management

What should you know about glomerular disease?

Glomerular hematuria/Glomerular proteinuria• Is it glomerular disease?

• What is the glomerular syndrome?

• What are the possible etiologies?

• What are the proper investigations?

• Management

Asymptomatic/Nephritis/Nephrotic

Primary/Secondary glomerular diseases

Urine exam/Complement/Serology/Kidney biopsy

General care/Immunosuppressive

drug/Plasmapheresis

Normal Glomerular Structure

Epithelial cell (podocyte)

Endothelial cell

Mesangial cell

Foot Process

1. Is it glomerular disease?

• Edema: salt water retention/ leakage edema

• High blood pressure: salt water retention

• Extra-renal manifestation (Etiology)

• Abnormal urine

• Glomerular proteinuria***

• Glomerular hematuria***

• Decrease urine volume

Glomerular Proteinuria

• Albuminuria (UA protein 3-4+)• UPCI/24 hr proteinuria > 2 g/day

Glomerular Hematuria

• Red/brown/Coca-Cola color• Total hematuria• Absent clot• RBC cast/Dysmorphic RBC• With significant proteinuria

Dysmorphic RBC• > 50% (phase-contrast) of RBC• > 80% (light microscopy) of RBC• Acanthocyte > 5%

2. Glomerular Syndrome

Asymptomatic urine abnormality

- Isolated proteinuria 150 mg – 3 g/day

- Hematuria > 2 RBC/HPF

Nephritis: Acute (< 2wk)/ Rapidly Progressive (2 wk to 3 mo)/ Chronic GN (> 3mo)

- Glomerular hematuria - Edema - High blood pressure

- Proteinuria - Oliguria - GFR decline

Nephrotic syndrome

- Proteinuria > 3.5 g/day - Hypercholesterolemia

- Hypoalbuminemia < 3.0 g/dL - Lipiduria (oval fat body)- Leakage edema

2. Glomerular Syndrome

Asymptomatic urine abnormality

- Alport’s Syndrome

- Thin Basement Membrane Disease- IgA Nephropathy

Nephritis: Acute (< 2wk)/ Rapidly Progressive (2 wk to 3 mo)/ Chronic GN (> 3mo)

- Immune Complex

- Pauci-immune- Anti-GBM disease

Nephrotic syndrome

- Minimal change disease (MCD) - Membranous Nephropathy

- Focal Segmental Glomerulosclerosis (FSGS) - Deposition disease (Amyloidosis)- Diabetes Nephropathy

3. Primary VS Secondary glomerular disease

Primary glomerular disease

• Idiopathic

• Pathological patterns

o MCD, FSGS, MN, MPGN, IgA Nephropathy

Secondary glomerular disease

• Underlying cause can be established

• Systemic disease involving multiple organs

o SLE, DM, Amyloidosis, Multiple myeloma

• Infection

o HIV, HBV, HCV, Syphilis, bacterial infection

• Drugs

o NSAIDs, Heroin, Penicillamine, Gold

• Malignancy

Nephrotic Syndrome

Differential diagnosis

(Pathological Pattern)

• Minimal change disease (MCD)

• Focal Segmental Glomerulosclerosis

(FSGS)

• Membranous Nephropathy

• Deposition disease (Amyloidosis)

• Diabetes Nephropathy

Criteria diagnosis

• Proteinuria > 3.5 g/day

• Hypoalbuminemia < 3.0 g/dL

• Leakage edema

• Hypercholesterolemia

• Lipiduria (oval fat body)

Minimal Change Disease (MCD)

• T-cell mediated soluble mediators

• Diffuse foot process effacement

• Abrupt onset nephrotic syndrome

Normal glomerulus MCD

Clin J Am Soc Nephrol 12: 332–345, February, 2017

Minimal Change Disease (MCD)

Key Points Details

Epidemiology Most common NS in children (70-90%) but less common in adults (15-20%)

Manifestations• Abrupt-onset NS, usually full-blown• Microhematuria rare in children, 10-30% in adults

Associations• Atopy/allergy• Malignancy (hematologic esp. Hodgkin disease)• Drugs (NSAIDS)

Pathology• LM: normal-looking glomeruli• EM: extensive podocyte foot process effacement

Treatment High dose steroid (1 mg/kg/d prednisolone) tapering over 6 months

Focal Segmental Glomerulosclerosis (FSGS)

• Focal (Some) Segmental (Sections) Glomerulosclerosis (Of

kidney are scarred)

• Podocyte injury and podocyte loss

• Foot process effacement and Scar

• Abrupt onset Nephrotic syndrome in primary FSGS

• Manifestations vary in secondary FSGS

CJASN March 2017, 12 (3) 502-517

Focal Segmental Glomerulosclerosis (FSGS)

Key Points Details

Epidemiology Top 2 most common NS in adults (30-35%)

Manifestations• Abrupt NS in 1o FSGS• Asymptomatic proteinuria to insidious onset NS in 2o FSGS• Microhematuria common in adults (> 50%)

Associations

• Genetic: APOL1 (African American)• Infection: HIV, Parvovirus B19, CMV, EBV• Drugs: bisphosphonate, heroin, lithium, IFN therapy• Adaptive: glomerular hyperfiltration

o Decreased nephron: Single kidneyo Normal nephron mass (Hyperfiltration): Obesity, DM, HTN

Pathology LM: segmental sclerosis, glomerular tuft adhesion

Treatment High dose steroid (1 mg/kg/d prednisolone) tapering over 6 months

Time-to-response to prednisone is much shorter in children than in adults

Steroid resistant (adult)Steroid resistant (children)

Steroid resistant Nephrotic syndrome in Adult:

≥ 16 weeks

Median time to response in adult: 8 weeks (8 days in

children)

Infrequent relapses (< 2 relapses per 6 mo):

Prednisolone 1 MKD

Frequent relapses (≥ 2 relapses per 6 mo):

Cyclophosphamide 2–2.5 mg/kg per d for 8 wk

Clin J Am Soc Nephrol 12: 332–345, February, 2017

Membranous Nephropathy (MN)

• Subepithelial immune deposit

• Podocyte injury and glomerular basement membrane changes

Ronco P. Pathogenesis of membranous nephropathy: Recent advances and future challenges. Nature reviews 2013

Normal glomerulus MN

Membranous Nephropathy (MN)

Key Points Details

Epidemiology Top 2 most common NS in adults (30-35%)

Manifestations• Insidious/chronic NS in adults• Microhematuria common in adults (30-50%)

Associations

1o MN: PLA2R Ab (50-70%)2o MN:• Infection (HBV*, HCV, HIV, syphilis, malaria, schistosomiasis, filariasis)• Malignancy (lung, prostate, colon)• Any autoimmune diseases (SLE, Sjogren) • Alloimmune disease (GVHD)• Drugs (gold, penicillamine, NSAIDS)

Pathology• LM: diffuse regular GBM thickening• EM: subepithelial electron dense deposits

Treatment

Membranous Nephropathy (MN)

1o MN 2o MN

• Supportive care (BP control, RASB, statin, diuretics, salt restriction)

• Treat underlying systemic disease (HBV, HCV, HIV, Syphilis, malignancy)

• Supportive care (3-6 mo)• Consider Immunosuppressive therapy only in:

o persistent proteinuria > 4 g/d after 6 moo severe, life-threatening nephrotic syndromeo Cr rising ≥ 30% in 6-12 mo

o Avoid Immunosuppressive in:o Cr > 3.5 mg/dL + small kidney size (< 8 cm)o concomitant severe infection

• Modified Ponticelli’s Regimen**• Oral Cyclophosphamide/steroid (6 mo

alternating monthly cycles)• CNI (cyclosporin, tacrolimus) + steroid• Rituximab

IdiopathicPLA2R Ab positive

KDIGO Clinical Practice Guidelines for Glomerulonephritis 2012

Amyloidosis

Soluble precursor(unstable)

Misfoldingintermediate

Aggregation into amyloid fibrilsin body tissues and organs

Peri-orbital purpura

Macroglossia

Deltoid pseudohypertrophy

Bilateral carpal tunnel syndrome

Low voltage (limb leads)

Pseudo-infarction (Q wave in chest leads)

HepatomegalyGastroparesis

Autonomic dysfunction (Dizziness, orthostatic)

Comprehensive Clinical Nephrology 6th Edition

Amyloidosis

Soluble precursor(unstable)

Misfoldingintermediate

Aggregation into amyloid fibrilsin body tissues and organs

Apple green birefringent on Congo red stain

Comprehensive Clinical Nephrology 6th Edition

Amyloidosis

Key Points Details

Epidemiology• The most common glomerular diseases associated with M-protein• Median age at diagnosis ~60+ years

Manifestations• Insidious onset NS in elderly• Extrarenal manifestations**: heart, neuro, skin, others

Associations• Monoclonal B lymphocyte/plasma cell proliferation• Multiple myeloma

Pathology Congo red: Apple green birefringent

Treatment Chemotherapy and Stem cell transplantation

Nephrotic Syndrome

Diseases Onset Age HematuriaSteroid

response

Minimal change disease Abrupt Adult+/-

+++

Focal segmental glomerulosclerosis

Abrupt in 1o

Insidious in 2o Adult +++ ++

Membranous nephropathy Insidious Elderly ++ +

Diabetic nephropathy Insidious DM +/- -

Amyloidosis Insidious Elderly +/- +

Nephrotic Syndrome

Nephrotic syndrome

• Onset/ Treatment responses• Hematuria• Extra-renal manifestation• Demographic data

Investigation

Treatment

Leakage edemaProteinuria > 3.5 g/day

Hypoalbuminemia

MCDFSGSMNDN

Amyloidosis

• Infection• Autoimmune• Malignancy• Drug• Systemic organ

involvement

• HBV, HCV, HIV, VDRL• ANA• Monoclonal gammopathy

(SPEP, IF, free light chain)• Pathology

o Kidney o Other organs

(Abdominal fat pad, bone marrow)

• Identify Etiology• Primary/Secondary

Quiz 1

• A 30-year-old man presented with foamy urine 2 weeks.

• PE: BP 120/70 mmHg, edema 3+

• U/A: protein 4+, WBC 0-1/HP, RBC 0-1/HP, UPCR 7

• Cr 1.0 mg/dL Alb 2.2 g/dL

What is the MOST likely renal biopsy finding?

A. Minimal change disease

B. IgM nephropathy

C. Amyloidosis

D. Membranoproliferative GN

E. IgA Nephropathy

Quiz 2

• A 30-year-old man presented with foamy urine 2 weeks.

• Renal biopsy: Minimal Change Disease

• On prednisolone 1 MKD 4 weeks

• U/A: protein 2+, WBC 0-1/HP, RBC 0-1/HP, UPCR 4

• Cr 1.0 mg/dL Alb 2.6 g/dL

What is the MOST appropriate treatment?

A. Add cyclophosphamide

B. Continue prednisolone 1 MKD

C. Add Enalapril

D. Repeat kidney biopsy

E. Add cyclosporin

Quiz 3

• A 30-year-old man presented with foamy urine 2 months.

• PE: BP 120/70 mmHg, edema 3+

• U/A: protein 4+, WBC 0-1/HP, RBC 0-1/HP, UPCR 7

• Cr 1.0 mg/dL Alb 2.2 g/dL

• He had history of jaundice 6 weeks ago due to viral hepatitis B

What is the MOST appropriate treatment?

A. Minimal change disease

B. Membranous nephropathy

C. Amyloidosis

D. Membranoproliferative GN

E. IgA nephropathy

Quiz 4

• A 50-year-old man presented with frothy urine for 2 months.

• PE: BP 120/70 mmHg, no edema

• U/A: protein 2+, WBC 0-1/HP, RBC 2-3/HP, UPCR 2.5

• Cr 1.0 mg/dL

• Renal biopsy: membranous nephropathy

What is the MOST appropriate treatment?

A. Prednisolone

B. Prednisolone + MMF

C. Prednisolone + cyclophosphamide

D. Enalapril

E. No treatment

Quiz 5

• A 65-year-old woman presented with fatigue and back pain.

• PE: BP 130/80 mmHg, moderately pale, pitting edema 3+ both legs.

• U/A: sp.gr. 1015, protein 4+, WBC 2-3/HP, RBC 0-1/HP.

• CBC: Hct 20%, WBC 5,400/mm3 (N 75%, L 25%) Plt 125,000/mm3.

• BUN 26 mg/dL, Cr 1.5 mg/dL, Albumin 2.8 g/dL, Globulin 5.5 g/dL.

What is the MOST appropriate next test?

A. Membranous nephropathy

B. Focal segmental glomerulosclerosis

C. Minimal change disease

D. Amyloidosis

E. Myeloma cast nephropathy

Quiz 6

• A 71-year-old man presented with weight loss, dizziness upon standing, sensorimotor peripheral neuropathy, and bilateral leg edema 2+.

• Cr 3.0 mg/dL

• U/A: sp.gr. 1015, protein 3+, WBC 2-3/HP, RBC 0-1/HP

What is the MOST appropriate next test?

A. CT abdomen

B. Peripheral nerve biopsy

C. Small intestine radiography

D. Bone marrow aspiration and biopsy

E. Fat pad with Congo red staining

Nephritis

Mesangial proliferative GN Diffuse proliferative GN Crescentic GN

Diagnostic approach by the key pathogenesis

All nephritic diseases are capable of causing all

patterns of glomerular injury

Nephritis: approach by pathogenesis

Glomerulonephritis

Glomerular hematuriaProteinuria Azotemia

Salt-water retention (edema, HTN)

Immune complexPauci-immune

(ANCA)Anti-GBM Mimicker

Classical pathway (Low C3, C4)- Autoimmune disease (Lupus Nephritis)- Cryoglobulinemic GN

Alternative pathway (Low C3, normal C4)- Post infectious GN

Lectin pathway (normal C3, C4)- IgA nephropathy

Normal C3, C4

AIN/ATN

Crystal-induced nephropathy

Myeloma cast nephropathy

TMA

Lupus Nephritis

Genetic + Environment factors

Circulating Immune complexAutoantibodies - Nuclear antibodies

Deposition of Immune complex in glomeruli

Mesangial proliferative GN (II)

Endocapillary GN (III/IV)

Membranous pattern (V)

Mesangial deposit

Subendothelial IC

Subepithelial IC

CJASN May 2017, 12 (5) 825-835

2012 SLICC criteria

Clinical criteria Immunological criteria

• Acute cutaneous lupus (malar, bullous)• Chronic cutaneous lupus (discoid,

panniculitis)• Oral ulcer• Non-scarring alopecia• Synovitis (2 or more joints)• Serositis (pleural/pericardial)• Renal (proteinuria > 500 mg/d or RBC

cast)• Neurologic (seizure, psychosis,

mononeuritis multiplex)• Hemolytic anemia• Leukopenia (WBC < 4,000/mm3 or

lymphopenia < 1,000/mm3)• Thrombocytopenia (<100,000/mm3)

• ANA positive• Anti-dsDNA above cutoff• Anti-Sm• Antiphospholipid ab• Low complement• Direct Coomb’s test positive (absence

of AIHA)

Diagnosis:• ≥ 4 criteria (at least 1 clinical &

immunologic criteria each) OR• Biopsy proven LN with positive ANA

or anti-dsDNA

Arthritis Rheum 2012; 64:2677-2686

2019 EULAR/ACR criteria

• All patients classified as having SLE must have serum ANA ≥ 1:80 on Hep-2 cells or an equivalent positive test

• Classify as SLE with a score of 10 or more

• Sensitivity 98% and Specificity 96% (SLICC: sensitivity 97% and specificity 90%)

EULAR/ACR CLASSIFICATION CRITERIA FOR SLE

Lupus Nephritis

Class IMinimal

mesangial GN

Class IIMesangial

proliferative GN

Class III/IVFocal/Diffuse

proliferative GN

Class VMembranous

pattern

Immune complex deposit with full house IF pattern

Not associated with long-term kidney impairment

ESRD 75-80% in 10 yr ESRD 8-12% in 10 yr

(without treatment)

CJASN May 2017, 12 (5) 825-835

Lupus Nephritis

Key Points Details

Epidemiology• The most common 2o glomerular diseases• Female : male = 8-15 : 1; Age 15-45 years

Manifestations

• Renal manifestationso Asymptomatic urinary abnormalities (class I, II)o Nephritis, mild (class III) or moderate-to-severe (class IV)o Nephrotic syndrome (class V)

• Extrarenal manifestations

Associations• ANA (90-95%), anti-dsDNA (75%), anti-sm (25-30%)• Low C3 & C4 (classical pathway complement activation)

Pathology• LM: minimal mesangial to diffuse proliferative & crescentic GN• IF: Full-house immune deposits (IgG, IgM, IgA, C1q, C3)

Treatment• Immunosuppressive drug• HCQ• Supportive therapy

Lupus Nephritis: Treatment

Immunosuppressive (IS)

Class I/II • As dictated by Extrarenal manifestations of lupus• Only in patients with Nephrotic syndrome

Class III/IV Induction• IV cyclophosphamide

• 0.5-1.0 g/m2 monthly x 6 cycles (NIH)**• 500 mg q 2 weeks x 6 cycles (EUROLUPUS)

• MMF 2-3 g/day for 6 monthsMaintenance• MMF 1-2 g/day• Azathioprine 1.5-2.5 mg/kg/day• Calcineurin inhibitor (cyclosporin, tacrolimus)

Class V Only in patients with persistent nephrotic syndrome

Class VI No IS

All patients with LN of any class are

treated with hydroxychloroquine

(maximum daily dose of 6–6.5

mg/kg ideal body weight), unless

they have a specific contraindication

to this drug.

CJASN May 2017, 12 (5) 825-835

Lupus Nephritis in Pregnancy

Can use in pregnancy Contraindicated in pregnancy

Corticosteroid Cyclophosphamide

Hydroxychloroquine MMF

Azathioprine ACEi/ARB

Calcineurin inhibitor

IVIg

• If on MMF switch to azathioprine

• If LN patients relapse during pregnancy treat with corticosteroids and azathioprine.

• If pregnant patients are receiving corticosteroids or azathioprine, do not taper IS during pregnancy or for at least 3 months after delivery.

• Complete remission before conception!!

• Add aspirin by 12 weeks to reduce risk of preeclampsia

CJASN May 2017, 12 (5) 825-835

Quiz 7

• A 24-year-old SLE woman with clinically inactive disease for the last few years was taking 10 mg/day of prednisolone and chloroquine 250 mg on alternate day.

• She became pregnant for 16 weeks.

• U/A: protein 1+, with cellular cast; Cr 0.8 mg/dL

• Hct dropped to 30% with spherocytes and polychromasia 1+

What is the MOST appropriate treatment?

A. Add ACEi

B. Increase prednisolone

C. Switch chloroquine to hydroxychloroquine

D. Switch chloroquine to azathioprine

E. Closed follow up and no treatment change

Cryoglobulinemia

Cryoglobulin: proteins (mostly immunoglobulins) that clump together in the cold temp

Type I Monoclonal IgM or IgGIgM IgG Lymphoproliferative disorders, MGUS

Waldenstrom’s macroglobulinaemia,

Type IIMonoclonal IgM

(rheumatoid factor activity) and Polyclonal IgG

Polyclonal IgM and Polyclonal IgG

Infection (HCV > HBV), autoimmune diseases,

lymphoproliferative disorders, essential

Type II

Mixed cryoglobulinemic GN

Cryoglobulinemia

Type I (monoclonal cryoglobulinemia)

Vascular occlusion > vasculitisRaynaud’s phenomenon

digital necrosisHyperviscosity syndrome

Type II/III (mixed cryoglobulinemia)

VasculitisPurpura (distal part), arthralgia,

peripheral neuropathy, Glomerulonephritis (MPGN)

Serum Cryoglobulin (++)Rheumatoid factor positive

Low C3, Very low C4

Serum Cryoglobulin (++++)

4oC 37oCPostgrad Med J 2007;83:87–94

Mixed Cryoglobulinemia

Key Points Details

Manifestations

• Renal manifestationso Nephritonephrotic syndrome

• Extrarenal manifestations: o palpable purpura, Raynaud’s, distal ulcer/necrosis, arthralgia/arthritis

peripheral neuropathy

Associations

• HCV infection 70-90% of cases with mixed cryoglobulinemia• Others: HBV, infective endocarditis, CTD, lymphoma, CLL• Presence of cryoglobulin with rheumatoid factor activity positive• Low C3 and very low C4

Pathology LM: membranoproliferative pattern, cryoplug

Treatment• Corticosteroid + rituximab/cyclophosphamide +/- plasmapheresis• Treat U/D: HCV

Quiz 8

• A 50-year-old woman with HCV infection presented with skin rash over both legs. She had upper respiratory tract infection 10 days ago.

• PE: BP 150/90 mmHg, PR 90/min, RR 20/min, BT 37.0 ºC

• BUN 25, Cr 2.2 mg/dL, C3 80 mg/dL (80-180), C4 10 mg/dL (20-50 )

• U/A: sp.gr. 1015, protein 3+, WBC 3-5/HP, RBC 30-50/HP.

• 24-hour urine protein 3 g/day

What is the MOST appropriate investigation?

A. ANA

B. ANCA

C. ASO titer

D. Anti-GBM disease

E. Serum cryoglobulin

Quiz 9

• A 44-year-old woman was evaluated for the abrupt onset of lower extremity rash.

• BP was 140/90 mmHg. There was multiple palpable purpura on the extremities.

• BUN 29 mg/dL, Cr 2.2 mg/dL, C3 42 mg/dL (88-206 mg/dL), C4 10 mg/dL (13-75 mg/dL)

• U/A protein 3+, dysmorphic RBC 20-30/HPF

• What is the MOST likely diagnosis?

A. ANCA associated vasculitis

B. Antiphospholipid syndrome

C. Cryoglobulinemic vasculitis

D. Henoch-Schonlein purpura

E. Acute Post-infectious glomerulonephritis

IgA NephropathyGalactose-deficient polymeric IgA1 and

anti-glycan antibody IgA-containing immune complex

Variable renal manifestations• Asymptomatic• Intermittent gross hematuria (Synpharyngitis)• Nephritis (RPGN, CGN)• Nephrotic syndrome (5%)• Extrarenal manifestation

Extra-renal manifestations• Cutaneous vasculitis • Abdominal pain

Treatment• Supportive care (RASB, BP <125/75 mmHg)• Prednisolone if persistent proteinuria > 1 g/d after 3-6 mo

Henoch-Schonlein purpura

J Am Soc Nephrol 22: 1795–1803, 2011

Quiz 10

• A 35-year-old woman presented with right flank pain for 1 days.

• She had had sore throat with fever 3 days earlier and took some antibiotics.

• PE: BT 38.5 ºC, BP 140/80 mmHg, pitting edema 1+.

• BUN 20, Cr 1.2 mg/dL, albumin 3.7 g/dL

• U/A: sp.gr. 1.020, protein 2+, WBC 5-10/HP, RBC 30-50/HP (dysmorphic).

What is the MOST likely diagnosis?

A. Acute post-streptococcal GN

B. IgA nephropathy

C. Acute interstitial nephritis

D. Renal calculi

E. Atheroembolic renal disease

Quiz 11

• A 32-year-old man presented with generalized edema for 3 days.

• Last week he had an abrasion wound at right ankle.

• BP 146/94 mmHg, pitting edema 2+ of both legs.

• BUN 18 mg/dL, Cr 1.2 mg/dL, C3 level 850 ug/mL (550-1200), C4 level 280 ug/mL (100-400)

• UA: protein 1+, RBC 30-50 /HPF, WBC 0-1 /HPF, UPCI 1.2

• What is the MOST likely diagnosis?

A. Lupus nephritis

B. IgA nephropathy

C. ANCA-associated vasculitis

D. Post-infectious GN

E. FSGS

Infection-related GN

Diffuse proliferative exudative GN

Subepithelial IC deposit Subepithelial hump

• Acute poststreptococcal GN 90% in children: good prognosis

• Staphylococcal infection more common in adults: poor prognosis

Renal manifestations• Acute nephritis with subnephrotic proteinuria

Extra-renal manifestations• Following pharyngitis (1-2 weeks) or skin infection (3 weeks) for APSGN• Concurrent infection in other forms; e.g. infective endocarditis, shunt

nephritis, other infections

Work up• Low C3, normal C4• ASO titer, Anti-DNaseB

Treatment• Supportive treatment (salt restriction, diuretics, anti-HT)• No evidence of immunosuppressive drug

ANCA-associated GN

ANCA disease

GPA(Wegener’s disease)

EGPA (Churg-Strauss)

Microscopic polyangiitis (MPA)

Renal limited vasculitis

Vasculitis with granulomac-ANCA (anti-PR3)

• Vasculitis with granuloma

• Asthma• Eosinophilia

p-ANCA (anti-MPO)

Vasculitis without granuloma

p-ANCA (anti-MPO)

Nephritis without systemic vasculitis

p-ANCA (anti-MPO)

GPA: Granulomatosis with PolyangiitisEGPA: Eosinophilic Granulomatosis with Polyangiitis

CJASN October 2017, 12 (10) 1680-1691

ANCA-associated GN

Key Points Details

Epidemiology The most common form of new-onset GN after 50 years

Manifestations

• Renal manifestationso RPGN or CGN with non-nephrotic range proteinuria

• Extrarenal manifestations: o fever, malaise, weight loss, systemic vasculitis

Associations• Drugs: hydralazine, PTU, levamisole-adulterated cocaine• Double positive disease: anti-GBM disease, SLE

Pathology• LM: Necrotizing & crescentic GN +/- vasculitis• IF: pauci-immune deposit

Treatment

• Induction: Cyclophosphamide + corticosteroid• Maintenance: Azathioprine• Plasmapheresis

o Severe renal involvement (Cr > 5.6)o Alveolar hemorrhageo Double positive with anti-GBM

ANCA-associated GN

Organ involvements GPA EGPA MPA RLV

Constitutional symptoms: fever, malaise, weight loss, myalgia, arthralgia + + + +/-

RenalSevere(RPGN)

less severeSevere(RPGN)

Severe(RPGN)

Cutaneous• Palpable purpura (mainly lower extremities)• Subcutaneous nodules

++

++

+-

--

Respiratory tract• Upper: sinusitis, nasal septum collapse (saddle nose)• Lower:

• Pulmonary hemorrhage (alveolar capillaritits)• Necrotizing granuloma

+

++

+

++

-

+-

-

--

Neuro: peripheral neuropathy (mononeuritis multiplex) - + - -

Gastrointestinal: abdominal pain (mesenteric ischemia) + + + -

Serology P-ANCA C-ANCA C-ANCA C-ANCA

CJASN October 2017, 12 (10) 1680-1691

Quiz 12

• A 56-year-old man presented with progressive edema with low-grade fever, hemoptysis, and weight loss for 5 weeks.

• PE: BP 150/80 mmHg, generalised edema, palpable purpura spots on both legs, and right foot drop.

• BUN 56, Cr 2.8 mg/dL, albumin 4.2 g/dL, cholesterol 190 mg/dL

• U/A: protein 4+, WBC 3-5/HP, RBC 30-50/HP (dysmorphic), UPCR 1.8

• ESR 80 mm/h, normal serum complement study

What is the MOST useful serologic test?

A. Anti-dsDNA antibody

B. Anti-GBM antibody

C. Anti-neutrophilic cytoplasmic antibody

D. Anti-streptolysin O antibody

E. Anti-HCV antibody

Quiz 13

• A 50-year-old man presented with bloody crusting nasal discharge for 4 weeks.

• PE: ulcerated nasal mucosa and anemia.

• U/A: protein 1+, microscopic hematuria with RBC cast

• Cr 2.0 mg/dL

• c-ANCA positive, ESR 105 mm/hour

What is the MOST appropriate treatment?

A. IVIg

B. High dose prednisolone

C. MTX and prednisolone

D. Trimethoprim-sulfamethoxazole and prednisolone

E. Cyclophosphamide and high dose prednisolone

Anti-Glomerular Basement Membrane (Anti-GBM) disease

Necrotizing & crescentic GN Linear immune deposit along GBM

Autoantibody to Alpha3 chain type IV collagen

Renal manifestations• RPGN

Extra-renal manifestations• Alveolar hemorrhage

(Goodpasture’s syndrome)

Work up• Anti-GBM antibody • ANCA (double positive)

Treatment• Plasmapheresis• IV methylprednisolone• Cyclophosphamide

CJASN October 2017, 12 (10) 1680-1691

Nephritis

Glomerulonephritis

Glomerular hematuriaProteinuria Azotemia

Salt-water retention (edema, HTN)

Immune complexPauci-immune

Anti-GBMMimicker

• Heavy proteinuria?• Extra-renal manifestation• Demographic

• Rash• Systemic vasculitis (purpura,

mononeuritis multiplex, lung hemorrhage)

• Infection (Hx, active)• Systemic organ involvement

Prefer Immune complex

Investigation

• Complement• ANA, ANCA, Anti-GBM• Cryoglobulin, RF, HCV, HBV• Kidney biopsy

Treatment

Quiz 14

• A 28-year-old woman presented with confusion, anemia, and thrombocytopenia.

• CBC: Hb 8.5 g/dL, MCV 85 fL, WBC 11,000/mm3 (N 85%, L 15%), platelet 8,000/mm3.

• Peripheral blood smear: schistocytes

• Normal prothrombin time and activated partial thromboplastin time.

• UA: protein 2+

• Cr 1.5 mg/dL

What is the MOST appropriate treatment?

A. Heparin

B. Prednisolone

C. Plasmapheresis with albumin

D. Platelet and LPRC transfusion

E. Plasmapheresis with Fresh frozen plasma replacement

Quiz 15

• A 77-year-old man presented with increasing fatigue for 2 weeks.

• He had history of cardiac catheterization 1 month earlier.

• PE: pitting edema 1+, diminished posterior tibial and dorsalis pedis pulses bilaterally, bluish discoloration of the left and right great toes.

• U/A: protein 2+, WBC 1-2/HP, RBC 1-2/HP, rare granular cast

• Cr 3.6 mg/dL, C3 82 mg/dL (100-233), C4 15 mg/dL (14-48)

What is the MOST likely diagnosis?

A. Renal infarction

B. Contrast-induced nephropathy

C. Cholesterol emboli

D. Cryoglobulinemia

E. Post-infectious GN

Thank You For Your Attention

Good Luck For Your Examination