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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