Post on 19-Jan-2016
description
Nephrology Nephrology conferenceconference
報告人:報告人: R3 R3 王劭瑜王劭瑜指導老師:鄭昌錡醫師指導老師:鄭昌錡醫師
Case presentationCase presentation
A 46 years old male presented as A 46 years old male presented as
bilateral legs pain for 2 weeksbilateral legs pain for 2 weeks
Patient profilePatient profile
NameName ︰︰楊楊 XX 州州 AgeAge :: 46-year-old46-year-old GenderGender :: malemale Height/Weight: 170cm /75 kgHeight/Weight: 170cm /75 kg Occupation: WorkerOccupation: Worker Marriage status: marriedMarriage status: married HospitalizationHospitalization ::
2011/01/26~2011/04/162011/01/26~2011/04/16 Chart numberChart number :: 2141854421418544
Chief complaintChief complaint
Bilateral legs progressive pain for 2 Bilateral legs progressive pain for 2 weeksweeks
Present illnessPresent illness This 46 years old male has underlying This 46 years old male has underlying
of of Diabetes mellitus, type 2; Hypertension Diabetes mellitus, type 2; Hypertension
for 5 yearsfor 5 years=> medications control=> medications control
Chronic kidney disease? Etiology?Chronic kidney disease? Etiology?
Present illnessPresent illness Bilateral legs progressive pain for 2 weeksBilateral legs progressive pain for 2 weeks
=> Rehab clinic and Chinese herb (pain => Rehab clinic and Chinese herb (pain killer?) killer?)
Admission in Admission in 壢新壢新 H (2011/01/19)H (2011/01/19) : : Acute kidney injury => Hemodialysis twice due Acute kidney injury => Hemodialysis twice due
to hyperkalemia and acute pulmonary edemato hyperkalemia and acute pulmonary edema Kidney echo: bilateral large renal hypertrophy Kidney echo: bilateral large renal hypertrophy
with mild right hydronephrosiswith mild right hydronephrosis Dyspnea persistent refractory to emergent Dyspnea persistent refractory to emergent
hemodialysis, with sudden onset of hemodialysis, with sudden onset of hemoptysis on 1/25 & 1/26hemoptysis on 1/25 & 1/26
Present illnessPresent illness Associated symptoms: Associated symptoms:
Decreased urine outputDecreased urine output Progressive edema Progressive edema Poor appetite Poor appetite Chest pain over left chestChest pain over left chest
Negative findings: Negative findings: Recently surgical Recently surgical
procedures/trauma/immobilizationprocedures/trauma/immobilization Fever/chills/Purulent coughFever/chills/Purulent cough
Rhinorrhea/sorethroatRhinorrhea/sorethroat
Past historyPast history
Diabetes mellitus, type 2, for 5 yearsDiabetes mellitus, type 2, for 5 years Hypertension for 5 yearsHypertension for 5 years Operation history: Traffic accident 20 Operation history: Traffic accident 20
years agoyears ago Left leg fracture status post interlocking nailLeft leg fracture status post interlocking nail
Denied major systemic disease as coronary Denied major systemic disease as coronary artery disease, asthma, hepatitis B/C, artery disease, asthma, hepatitis B/C, peptic ulcer diseasepeptic ulcer disease
Medications: DM, HTN, Pain controller?Medications: DM, HTN, Pain controller?
Personal historyPersonal history
Allergy: no known allergyAllergy: no known allergy Alcohol: DeniedAlcohol: Denied Smoking: 0.5PPD for 10+ yearsSmoking: 0.5PPD for 10+ years Betalnut: DeniedBetalnut: Denied
Family HistoryFamily HistoryUnknown cancer history
Diabetes mellitusHeart disease
Physical examinationPhysical examination BT:36.5, PP:78/min, RR:18/min, BP:BT:36.5, PP:78/min, RR:18/min, BP:201/107201/107mmHgmmHg Appearance: alert, Appearance: alert, ill-lookingill-looking, E4V5M6, E4V5M6 Sclera: not icteric; Conjunctiva: paleSclera: not icteric; Conjunctiva: pale Neck: no stiffness, no lymphadenopathyNeck: no stiffness, no lymphadenopathy Chest: Chest: bilateral diffuse crackles, wheezing, bilateral diffuse crackles, wheezing,
ronchironchi Heart: regular heart beat without audible Heart: regular heart beat without audible
murmursmurmurs Abdomen: soft and flat, no tenderness, Abdomen: soft and flat, no tenderness,
normoactivenormoactive Extremities: free movable, Extremities: free movable, grade 2 pitting edemagrade 2 pitting edema
pulsation: symmetric pulsation: symmetric
HemogramHemogram 2011/01/2011/01/2626
WBCWBC 1000/uL1000/uL 12.712.7
HemoglobHemoglobinin
g/dLg/dL 6.76.7
HematocrHematocritit
%% 19.519.5
MCVMCV fLfL 75.975.9
PlateletsPlatelets 1000/uL1000/uL 266266
SegmentSegment %% 94.094.0
BandBand %% 2.02.0
LymphocyLymphocytete
%% 2.02.0
MonocyteMonocyte %% 1.01.0
EosinophiEosinophill
%% 0.00.0
BasophilBasophil %% 1.01.0
P.TP.T 13.6/10.13.6/10.77
INRINR 1.31.3
APTTAPTT 35.3/2635.3/26
BiochemistryBiochemistry 2011/01/2011/01/2626
BUN (B)BUN (B) mg/dLmg/dL 91.491.4
CreatininCreatininee
mg/dLmg/dL 10.0210.02
NaNa mEg/mEg/dLdL 130130
ClCl mEq/LmEq/L 9999
KKmEq/mEq/
dLdL 5.35.3
CaCa mg/dLmg/dL 8.08.0
PP mg/dLmg/dL 7.77.7
AlbuminAlbumin g/dLg/dL 2.712.71
TPTP g/dLg/dL 5.65.6
HbA1cHbA1c mg/dLmg/dL 6.66.6
Bilirubin Bilirubin (T)(T) mg/dLmg/dL 0.20.2
AST AST (GOT)(GOT) U/LU/L 1414
ALT/GPTALT/GPT U/LU/L 2323
ALK-PALK-P U/LU/L 163163
H/D on 1/24, 1/25
UrinalysisUrinalysis 2011/012011/01/28/28
ColorColor YellowYellow
SP.GravitSP.Gravityy
1.0131.013
pHpH 6.06.0
LeukocytLeukocytee
TraceTrace
NitriteNitrite NegativNegativee
ProteinProtein mg/dLmg/dL 2+ 2+ (100)(100)
GlucoseGlucose g/dLg/dL NegativNegativee
KetoneKetone NegativNegativee
UrobilinoUrobilinogengen EU/dLEU/dL 0.10.1
BilirubinBilirubin NegativNegativee
BloodBlood 3+3+
Hyaline Hyaline castcast /ul/ul 0-20-2
BacteriaBacteria PositivePositive
RBCRBC /uL/uL 63 63
WBCWBC /uL/uL 9090
Epithelial Epithelial /uL/uL 11
Arterial blood gasArterial blood gas 2011/012011/01/28/28
TempTemp ℃℃ 3737
pHpH 7.3017.301
PCO2PCO2 mmHgmmHg 33.133.1
PaO2PaO2 mmHgmmHg 72.672.6
HCO3HCO3 mm/Lmm/L 16.016.0
SBESBE mm/Lmm/L -10.4-10.4
SatSat %% 93.393.3
2011/01/26
Marked interstitial/airspace infiltration of both lungs, with diffuse patchy opacities. Favor ongoing inflammation
Tortuous thoracic aorta and borderline cardiomegaly
ImpressionImpression
Rapidly-progressing glomerulonephritisRapidly-progressing glomerulonephritis Hemoptysis, suspect pulmonary Hemoptysis, suspect pulmonary
hemorrhagehemorrhage Bilateral lower legs pain, cause to be Bilateral lower legs pain, cause to be
determinateddeterminated Microcytic anemiaMicrocytic anemia
Diabetes mellitus, type 2, HbA1c=6.6Diabetes mellitus, type 2, HbA1c=6.6 HypertensionHypertension
Rapidly-progressing Rapidly-progressing glomerulonephritisglomerulonephritis
2011/01/262011/01/26
ANAANA NegativeNegative
C3C3 mg/dLmg/dL 110 110 (90~180)(90~180)
C4C4 mg/dLmg/dL 17.8 17.8 (10~40)(10~40)
A-DSDNAA-DSDNA WHOunit/WHOunit/mLmL
<40.5 <40.5 (Negative)(Negative)
ANCAANCA C-ANCAC-ANCA Positive Positive
P-ANCAP-ANCA Negative Negative HBsAgHBsAg NegativeNegative
Anti-HCV Anti-HCV AbAb
NegativeNegative
RPRRPR NegativeNegative
HIV 1+2 AbHIV 1+2 Ab NegativeNegative
ASLOASLO IU/mLIU/mL <49.70 <49.70 (<200)(<200)
2011/01/262011/01/26
Total Total ProteinProtein
5.6 gm/dL5.6 gm/dL
AlbuminAlbumin 2.5 mg/dL (43.80%)2.5 mg/dL (43.80%)
αα1-1-globulinglobulin
0.5 mg/dL ( 9.40%)0.5 mg/dL ( 9.40%)
αα2-2-globulinglobulin
0.9 mg/dL (16.80%)0.9 mg/dL (16.80%)
ββ--globulinglobulin
0.7 mg/dL (12.70%)0.7 mg/dL (12.70%)
γγ--globulinglobulin
1.0 mg/dL (17.30%)1.0 mg/dL (17.30%)
A/GA/G 0.770.77
Protein loss or malnutrition Protein loss or malnutrition pattern pattern with decrease of protein and with decrease of protein and albuminalbumin
IFEIFE No paraprotein is No paraprotein is identifiedidentified
IgGIgG 976.00 mg/dl 976.00 mg/dl (700~1600)(700~1600)
IgAIgA 171.00 mg/dL 171.00 mg/dL (70~400)(70~400)
IgMIgM 51.60 mg/dL 51.60 mg/dL (40~230)(40~230)
IgEIgE 1030.00 1030.00 IU/mL(<100)IU/mL(<100)
Clinical courseClinical course
1/261/26 1/271/27 1/281/28 1/291/29 1/301/30 1/311/31 2/12/1 2/22/2 2/32/3 2/42/4
BuBunn
91.491.4 95.395.3 136.9136.9 150.8150.8 167.167.77
CrCr 10.0210.02 10.2810.28 11.4211.42 11.4311.43 11.611.6EExaxamm
HRCT
22DD CTACTA
Hydrocortisone 100mg q8h Heparin
Clinical courseClinical course
2/52/5 2/62/6 2/72/7 2/82/8 2/92/9 2/102/10 2/112/11 2/122/12 2/132/13 2/142/14
BuBunn
8383 103.4103.4
CrCr 6.646.64 7.367.36EExaxamm
DopplDopplerer
Kidney echo
Hydrocortisone 100mg q8h Heparin
Clinical courseClinical course
Hydrocortisone => PrednisoloneHydrocortisone => Prednisolone Heparin => WarfarinHeparin => Warfarin Channel ulcer bleeding (pyloric ring, GC site)Channel ulcer bleeding (pyloric ring, GC site)
PES failure => operation on 3/17PES failure => operation on 3/17 Discharge with OPD follow up on 4/16Discharge with OPD follow up on 4/16
1/26 4/5
c-ANCA
>400 u/ml
29.55 u/ml
p-ANCA
negative negative
DiagnosisDiagnosis
C-ANCA associated vasculitisC-ANCA associated vasculitis Deep vein thrombosisDeep vein thrombosis Channel ulcer bleeding, status post Channel ulcer bleeding, status post
endoscope and operationendoscope and operation Diabetes mellitus, type 2, Diabetes mellitus, type 2,
HbA1c=6.6HbA1c=6.6 HypertensionHypertension
DiscussionDiscussion
OutlineOutline
Pulmonary-renal syndromePulmonary-renal syndrome ANCA-associated VasculitidesANCA-associated Vasculitides Wegener's granulomatosisWegener's granulomatosis Diagnostic procedureDiagnostic procedure Case correlationCase correlation
Pulmonary Renal Pulmonary Renal SyndromeSyndrome
1919, Ernest Goodpasture: 1919, Ernest Goodpasture: A case of pulmonary hemorrhage and A case of pulmonary hemorrhage and glomerulonephritisglomerulonephritis
1955, Parkin:1955, Parkin:Lung hemorrhage and nephritis, absence of Lung hemorrhage and nephritis, absence of arteritisarteritis
1958, Stanton and Tang: 1958, Stanton and Tang: Pulmonary hemorrhage with glomerulonephritisPulmonary hemorrhage with glomerulonephritis
1950s, Krakower and Greenspun: 1950s, Krakower and Greenspun: Identified GBM as the antigenIdentified GBM as the antigen
1967, Lerner, Glassock, and Dixon: 1967, Lerner, Glassock, and Dixon: Anti-GBM antibodies => PathogenesisAnti-GBM antibodies => Pathogenesis
Pulmonary Renal Pulmonary Renal SyndromeSyndrome
Anti-GBM antibody disease Anti-GBM antibody disease (Goodpasture)(Goodpasture)
Systemic vasculitis: Wegener's Systemic vasculitis: Wegener's granulomatosisgranulomatosis
Acute glomerulonephritis: Acute glomerulonephritis: Complicated with pulmonary edemaComplicated with pulmonary edema Uremia-induced increase in Uremia-induced increase in
pulmonary capillary permeability pulmonary capillary permeability Pulmonary infectionPulmonary infection
1 Disease or 2 Diagnosis 1 Disease or 2 Diagnosis
Specks U. Diffuse alveolar hemorrhage syndromes CURR OPIN RHEUMATOL 2001;13:12-17
Pulmonary Renal Pulmonary Renal SyndromeSyndrome
The remaining patients had a variety The remaining patients had a variety of disorders including pulmonary of disorders including pulmonary emboli, infection, and lupusemboli, infection, and lupusNiles JL, Böttinger EP, Saurina GR, et
al. The syndrome of lung hemorrhage and nephritis is usually an ANCA-associated condition Arch Intern Med 1996; 156:440
ANCA 48: pauci-immune 48: pauci-immune glomerulonephritis with glomerulonephritis with pulmonary symptomspulmonary symptoms
8: good evidence for 8: good evidence for Wegener's granulomatosisWegener's granulomatosis
Anti-GBM Ab 6
Both 7
ANCA-associated ANCA-associated VasculitidesVasculitides
ClassificationsClassifications
Primary:Primary: Immune complex Immune complex
mediated mediated ANCAANCA
Secondary:Secondary: Connective tissue Connective tissue
disordersdisorders Viral infectionViral infection
Large-vessel VasculitisLarge-vessel Vasculitis
Giant cell (temporal) Giant cell (temporal) arteritisarteritis
Takayasu arteritisTakayasu arteritis
Medium-sized-vessel Medium-sized-vessel VasculitisVasculitis
Polyarteritis nodosaPolyarteritis nodosa
Kawasaki diseaseKawasaki disease
Small-vessel VasculitisSmall-vessel Vasculitis
WegenerWegener’’s s granulomatosisgranulomatosis
Churg-Strauss syndromeChurg-Strauss syndrome
Microscopic polyangiitisMicroscopic polyangiitis
Henoch-SchHenoch-Schöönlein purpuranlein purpura
Essential cryoglobulinemic Essential cryoglobulinemic vasculitisvasculitis
Cutaneous leukocytoclastic Cutaneous leukocytoclastic angiitisangiitis
Diagnostic criteriaDiagnostic criteria
The American College of Rheumatology (ACR)The American College of Rheumatology (ACR)Vessel size, Histopathology, Clinical symptomsVessel size, Histopathology, Clinical symptomsstudy criteria rather than diagnostic criteriastudy criteria rather than diagnostic criteria
Chapel Hill Consensus Conference (CHCC)Chapel Hill Consensus Conference (CHCC)Definitions, but not Diagnostic criteriaDefinitions, but not Diagnostic criteria
European Medicines Agency algorithm: European Medicines Agency algorithm: Watts et al. Watts et al. 20072007
ANCA: permit the diagnosis of WG ANCA: permit the diagnosis of WG in the absence of biopsy in the absence of biopsy
CCSS criteriaSS criteria WWG criteriaG criteria
Seronegative ANCA disease
Proteinase 3 ANCA diseaseMyeloperoxidase ANCA disease
Prognositc significance
Response to therapy
Porpensity for relapse
Patient outcome
Churg-Strauss syndrome Asthma (a history of wheezing or the finding
of diffus high pitched wheezes on expiration) Eosniophilia of > 10 % Mononeuropathy (including multiplex) or
polyneuropathy Miugratory or transient pulmonary opacities
detected radiographically Paranasal sinus abnormality Biopsy containing a blood vessel showing
the accumulation of eosinophils in extravascular areas
Wegener’s criteria
Nasal or oral inflammation (painful or painless oral ulcers or purulent or bloody nasal discharge)
Abnormal chest radiograph showing nodules, fixed infiltrates, or cavities
Abnormal urinary sediment (microscopic hematuria or red cell casts)
Granulomatous inflammation on biopsy of an artery or perivascular area
> 2 / 4 => Sensitivity: 88%; Specificity: 92%
PathogenesisPathogenesis
Abbreviations: Abbreviations: CD, cluster of differentiation; CTLA4, tyotoxic T-CD, cluster of differentiation; CTLA4, tyotoxic T-lymphocyte antigen4 gene;lymphocyte antigen4 gene;PTPN22, protein tyrosine phosphagase, non-receptor type PTPN22, protein tyrosine phosphagase, non-receptor type 22 gene22 gene
ANCAs in the pathogenesis ANCAs in the pathogenesis of AAVof AAV
Neonate glomerulonephritis and pulmonary Neonate glomerulonephritis and pulmonary hemorrhage:hemorrhage:Transplacental of ANCA IgG from the mother Transplacental of ANCA IgG from the mother
who had anti-MPO-antibody-positive MPAwho had anti-MPO-antibody-positive MPA ANCAs: serological markersANCAs: serological markers
cANCA: proteinase-3 (PR3) / cytoplasmiccANCA: proteinase-3 (PR3) / cytoplasmic pANCA: myeloperoxidase (MPO) / pANCA: myeloperoxidase (MPO) /
perinuclearperinuclear
PathogenesisPathogenesis
Abbreviations: Abbreviations: CD, cluster of differentiation; CTLA4, tyotoxic T-CD, cluster of differentiation; CTLA4, tyotoxic T-lymphocyte antigen4 gene;lymphocyte antigen4 gene;PTPN22, protein tyrosine phosphagase, non-receptor type PTPN22, protein tyrosine phosphagase, non-receptor type 22 gene22 gene
PathogenesisPathogenesis
Abbreviations: Abbreviations: CD, cluster of differentiation; CTLA4, tyotoxic T-CD, cluster of differentiation; CTLA4, tyotoxic T-lymphocyte antigen4 gene;lymphocyte antigen4 gene;PTPN22, protein tyrosine phosphagase, non-receptor type PTPN22, protein tyrosine phosphagase, non-receptor type 22 gene22 gene
Caucasians African-Americans German Netherlands Japan
PathogenesisPathogenesis
Abbreviations: Abbreviations: CD, cluster of differentiation; CTLA4, tyotoxic T-CD, cluster of differentiation; CTLA4, tyotoxic T-lymphocyte antigen4 gene;lymphocyte antigen4 gene;PTPN22, protein tyrosine phosphagase, non-receptor type PTPN22, protein tyrosine phosphagase, non-receptor type 22 gene22 gene
Respiratory tract: Silica exposure Accdelerated apoptosis of PolyMorphoNuclear and Macrophages: a trigger in the development of AAV
PathogenesisPathogenesis
Abbreviations: Abbreviations: CD, cluster of differentiation; CTLA4, tyotoxic T-CD, cluster of differentiation; CTLA4, tyotoxic T-lymphocyte antigen4 gene;lymphocyte antigen4 gene;PTPN22, protein tyrosine phosphagase, non-receptor type PTPN22, protein tyrosine phosphagase, non-receptor type 22 gene22 gene
Staphylococcus aureus: strongest association Superantigens from S. aureus: stimulate B & T cells, leading to AAV Directly prime neutrophils => membrance expression of PR3Gram-negative bacteria: E. coli & K. pneumoniae LAMP-2 antibiotis: homologous to the bacterial adhesion protein FimH (Lysosomal membrane protein 2)
PathogenesisPathogenesis
Abbreviations: Abbreviations: CD, cluster of differentiation; CTLA4, tyotoxic T-CD, cluster of differentiation; CTLA4, tyotoxic T-lymphocyte antigen4 gene;lymphocyte antigen4 gene;PTPN22, protein tyrosine phosphagase, non-receptor type PTPN22, protein tyrosine phosphagase, non-receptor type 22 gene22 gene
Anti-Plasminogen antibodies — correlates with both venous thromboembolic events and with characteristic glomerular histologic lesions and reduced renal function
Granulomatosis with Granulomatosis with polyangiitispolyangiitis
(Wegener (Wegener’’s granulomatosis)s granulomatosis)
BackgroundBackgroundClinical manifestationsClinical manifestations
DiagnosisDiagnosisTreatmentTreatment
BackgroundBackground 1897, Peter McBride: the first written description1897, Peter McBride: the first written description 1931, Klinger: 70-year-old physician with 1931, Klinger: 70-year-old physician with
constitutional symptoms, joint symptoms, proptosis, constitutional symptoms, joint symptoms, proptosis, widespread upper respiratory tract inflammation widespread upper respiratory tract inflammation leading to saddle nose deformity, leading to saddle nose deformity, glomerulonephritis and pulmonary lesionsglomerulonephritis and pulmonary lesions
1936, Dr. Frederich 1936, Dr. Frederich WegenerWegener: : Distinct clinical and histopathologic findingsDistinct clinical and histopathologic findings
1954, Goodman and Churg: triad1954, Goodman and Churg: triad Systemic necrotizing angiitisSystemic necrotizing angiitis Necrotizing granulomatous inflammation of the Necrotizing granulomatous inflammation of the
respiratory tractrespiratory tract Necrotizing glomerulonephritisNecrotizing glomerulonephritis
2011: Granulomatosis with polyangiitis (Wegener2011: Granulomatosis with polyangiitis (Wegener’’s)s)
Epidemiology Epidemiology Frequency: rare disease, indeterminate Frequency: rare disease, indeterminate
incidenceincidencePrevalence in United States: 3/100,000Prevalence in United States: 3/100,000
Mortality: disease severity, intensity of TxMortality: disease severity, intensity of Tx Untreated: mean survival=5monthsUntreated: mean survival=5months
1-year mortality rate: 11% (2.2~25%)1-year mortality rate: 11% (2.2~25%)5-year survival rate: 74~79%5-year survival rate: 74~79%
Cause of death: infection, respiratroy & renal failure, Cause of death: infection, respiratroy & renal failure, malignancy and cardiovascular eventsmalignancy and cardiovascular events
Morbidity: currently treatment relatedMorbidity: currently treatment related Race: White individualsRace: White individuals Sex: European populations male-to-female=1.5:1Sex: European populations male-to-female=1.5:1 Age: occur at any age, typically 35~55 years oldAge: occur at any age, typically 35~55 years old
Phillip R, Luqmani R. Mortality in systemic vasculitis: a systematic review. Clin Exp Rheumatol. September-October 2008;26:S94-S104
Clinical presentationClinical presentation
Constitutional symptoms: Constitutional symptoms: fever, migratory arthralgias, malaise, fever, migratory arthralgias, malaise, anorexia and weight lossanorexia and weight loss
Prodromal symptoms: Prodromal symptoms: weeks to months without specific organ weeks to months without specific organ involvementinvolvement
Ear, Nose and ThroatEar, Nose and Throat PulmonaryPulmonary RenalRenal CutaneousCutaneous
ENTENT
Nasal crusting, Nasal crusting, sinusitis, otitis media, sinusitis, otitis media, persistent rhinorrhea, persistent rhinorrhea, oral or nasal ulcers, oral or nasal ulcers, purulent/bloody nasal purulent/bloody nasal discharge, discharge, polychondritispolychondritis
Saddle nose Saddle nose deformitydeformitymore typically in WGmore typically in WG
Pulmonary diseasePulmonary disease Airways and/or Pulmonary parenchyma: Airways and/or Pulmonary parenchyma:
hoarseness, cough, dyspnea, stridor, hoarseness, cough, dyspnea, stridor, wheezing, hemoptysis or pleuritic pain; wheezing, hemoptysis or pleuritic pain; tracheal or subglottic stenosis, tracheal or subglottic stenosis, pulmonary consolidationpulmonary consolidation Nodules and patchy or diffuse opacitiesNodules and patchy or diffuse opacities Pulmonary fibrosis and pulmonary Pulmonary fibrosis and pulmonary
hypertensionhypertension Tumor-like masses, extrathoracicTumor-like masses, extrathoracic
BreastBreast KidneyKidney
Renal diseaseRenal disease
Acute kidney injury with hematuria, red Acute kidney injury with hematuria, red cell and other casts, and proteinuriacell and other casts, and proteinuria
Classifications and outcome:Classifications and outcome: Focal: > 50% of glomeruli are normalFocal: > 50% of glomeruli are normal Crescentic: cellular crescentsCrescentic: cellular crescents Sclerotic: > 50% of glomeruli are globally Sclerotic: > 50% of glomeruli are globally
scleroticsclerotic Mixed: normal; crescentic; globally scleroticMixed: normal; crescentic; globally sclerotic
Renal biopsyRenal biopsy
• Segmental necrotizing glomerulonephritis
• GPA: Granulomatous changes
• Almost all Pauci-immune crescentic glomerulonephritis are ANCA positive
AANCA-negative pauci-NCA-negative pauci-immune GNimmune GN
AAs part of spectrum of WG and MPAs part of spectrum of WG and MPAsimilar renal biopsy findings and similar renal biopsy findings and prognosisprognosis Significnatly youngerSignificnatly younger Significantly higher rate of proteinuriaSignificantly higher rate of proteinuria Significantly lower rate of renal survival Significantly lower rate of renal survival
and of extrarenal manifestations and of extrarenal manifestations (pulmonary)(pulmonary)
Renal-limited vasculitisRenal-limited vasculitis
Indistinguishable histopathologic Indistinguishable histopathologic findingsfindings
More glomerulosclerosis changeMore glomerulosclerosis change LLate stage, in the absence of extral-ate stage, in the absence of extral-
renal presentationsrenal presentations
Cutaneous manifestations
Urticaria, livida reticularis and tender nodules
Leukocytoclastic angiitis, which cause purpura involving lower extremities
Focal necrosis and ulceration
Diagnostic approach
History & physical examinations Laboratory investigation
Antineutrophil cytoplasmic antibodies Urinalysis
Radiographic tests Tissue biopsy
Tissue biopsy
Tissue biopsy
Tissue diagnosis may not be required if the clinical gestalt is convincing and a sit for biopsy is not apparent or would be too invasive to obtainLeukocytoclasic vasculitis + pulmonary nodule + c-ANCA
Initiation of therapy without confirmatory biopsy Ventilator-dependent without extrapulmonary
involvelung biopsy when stable
Anti-neutrophil cytoplasmic antibodies
1982, Davies et al.: 1982, Davies et al.: First described in pauci-immune First described in pauci-immune glomerulonephritisglomerulonephritisbelieved associated with Ross River virus believed associated with Ross River virus infectioninfection
1985, link to granulomatosis with polyangiitis1985, link to granulomatosis with polyangiitis
Two types of ANCA assaysTwo types of ANCA assays Indirect immunofluorescence assay: more sensitiveIndirect immunofluorescence assay: more sensitive Enzyme-linked immunosorbent assay (ELISA): Enzyme-linked immunosorbent assay (ELISA):
specificspecific
Immunofluorescence
Subjective interpretation Unstandardized, references for
normal ranges Tertiary care centers with research
laboratories High sensitivity but not specific
Antibodies to azurophilic granule proteins
False positive in individuals with ANA
Comparison of tests for ANCAComparison of tests for ANCA
c-ANCAc-ANCA p-ANCAp-ANCAAntibodies to neutral proteins or Antibodies to neutral proteins or weak cations (e.g., proteinase 3)weak cations (e.g., proteinase 3)
Antibodies to strong cationsAntibodies to strong cations
Target antigen: protinease 3Target antigen: protinease 3 Target antigen: usually Target antigen: usually myeloperoxidase but nonspecific myeloperoxidase but nonspecific antigenic interactions occurantigenic interactions occur
Highly specific for Highly specific for WegenerWegener’’s granulomatosiss granulomatosis
Most often positive in patients Most often positive in patients with Microscopic polyangiitis or with Microscopic polyangiitis or Pauci-immune, rapidly Pauci-immune, rapidly progressive glomerulonephritisprogressive glomerulonephritis
Positive in 70~90% of patients Positive in 70~90% of patients with Wegenerwith Wegener’’s granulomatosiss granulomatosis
Positive in approximately 50% of Positive in approximately 50% of patietns with microscopic patietns with microscopic polyantiitispolyantiitis
Occasionally positive in patients Occasionally positive in patients with Microscopic polyangiitis or with Microscopic polyangiitis or the Churg-Strauss syndrome the Churg-Strauss syndrome (15~25%)(15~25%)
Positive in 5~30% of patient with Positive in 5~30% of patient with WegenerWegener’’s granulomatosiss granulomatosis
Very rarely positive in patients Very rarely positive in patients with certain infections disease with certain infections disease (e.g., amoebiasis)(e.g., amoebiasis)
May be positive in patients with May be positive in patients with Systemic Lupus Erythematosus, Systemic Lupus Erythematosus, GoodpastureGoodpasture’’s syndrome, s syndrome, inflammatory bowel disease, or inflammatory bowel disease, or rheumatoid arthritisrheumatoid arthritis
Clinical applications
Diagnostic value: Positive predictive value / Negative
predictive value Preclude the need of biopsy?
ANCA titer with disease activity
ANCA
Predictive value of ANCA varied markedly depending on the degree of renal disease at presentation
Clinical presentation Prevalence of PI-CGN PPV for PI-CGN NPV for PI-CGN
Rapidly progressive glomerulonephritis* 47 percent (106/224) 98 percent 80 percent
Hematuria, proteinuria, and creatinine >3 mg/dL 21 percent (181/862) 92 percent 93 percent
Hematuria, proteinuria, and creatinine 1.5-3 mg/dL 7 percent (51/685) 77 percent 98 percent
Hematuria, proteinuria, and creatinine <1.5 mg/dL 2 percent (13/768) 47 percent 99 percent
Rapidly progressive glomerulonephritis* 66 percent (82/124) 99 percent 65 percent
Hematuria, proteinuria, and creatinine >3 mg/dL 30 percent (147/497) 95 percent 89 percent
Hematuria, proteinuria, and creatinine 1.5-3 mg/dL 11 percent (36/311) 85 percent 97 percent
Hematuria, proteinuria, and creatinine <1.5 mg/dL 4 percent (7/195) 66 percent 99 percent
Rapidly progressive glomerulonephritis* 48 percent (10/21) 98 percent 80 percent
Hematuria, proteinuria, and creatinine >3 mg/dL 16 percent (6/38) 90 percent 95 percent
Hematuria, proteinuria, and creatinine 1.5-3 mg/dL 15 percent (6/39) 89 percent 95 percent
Hematuria, proteinuria, and creatinine <1.5 mg/dL 1 percent (1/162) 30 percent 100 percent
> 18 y/o
> 50 y/o
< 18 y/oDiagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idopathic systemic vasculitis. EC/BCR Project for ANCA ASSAy Standardization. Kidney Int 1998; 53:743 Hagen EC et al.
Diagnostic predictive value of ANCA serology. Kidney Int 1998; 53: 796 Jannette JC et al.
ANCA level and Disease ANCA level and Disease activityactivity
ControversialControversial ANCA levels & disease relapse from 0-20 ANCA levels & disease relapse from 0-20
monthsmonths Multicenter prospective cohort study: Multicenter prospective cohort study:
c-ANCA↓not associated with a shorter time c-ANCA↓not associated with a shorter time to remissionto remissionc-ANCA↑not associated with relapsec-ANCA↑not associated with relapse
Treatment decisions: donTreatment decisions: don’’t base on t base on ANCA titersANCA titers Finkielman, J. D. Finkielman, J. D. et alet al. Antiproteinase 3 . Antiproteinase 3
antineutrophil cytoplasmic antibodies antineutrophil cytoplasmic antibodies and disease activity in Wegener and disease activity in Wegener granulomatosis. granulomatosis. Ann. Intern. Med. Ann. Intern. Med. 147, 147, 611-619 (2007)611-619 (2007)
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Summery
Pulmonary-renal syndrome Diagnostic procedure:
Differential diagnosis C-ANCA ; Tissue biopsy
Treatment associated complications
Thank you for your Thank you for your attentionattention
High resolution computed High resolution computed tomographytomography
High resolution computed tomography
Kidney echoLeft Kidney Length: 13.2 cm Right Kidney Length: 13.3 cm Both kidneys are large and swollen in
appearance The cortical echogenicity increased to the level of liver The papillae is prominent The pelvocalyceal systems of kidneys are mildly dilatedNo renal stone, mass or hydronephrosis is noted
Impression: C/W Acute parenchymal renal disease Bilateral large kidneys Bilateral pelviectasis to mild hydronephrosis status
Treatment courseTreatment course Fortum 1/26~; Teico 1/27Fortum 1/26~; Teico 1/27 Consult Derma/Hema 1//28Consult Derma/Hema 1//28 Crofibrinogen/crioglobulin 1/31Crofibrinogen/crioglobulin 1/31 CTA 2/3; Consult Plasty 2/3 acute compartment syndromwCTA 2/3; Consult Plasty 2/3 acute compartment syndromw Consult CVS 2/3; Heparin 2/3Consult CVS 2/3; Heparin 2/3 Duppler 2/7; 3/26Duppler 2/7; 3/26 Kidney echo 2/11Kidney echo 2/11 Warfarin 2/17~Warfarin 2/17~ Symptoms improve after steroid: Hydrocortisone 100mg q8h Symptoms improve after steroid: Hydrocortisone 100mg q8h
1/27; q12h 2/20~2/25; Prednisolon 5mg 7# BID => 6# BID 1/27; q12h 2/20~2/25; Prednisolon 5mg 7# BID => 6# BID 3/12 => 8# QD 3/17; hydrocortisone 1# q12h 3/18 => QD 3/12 => 8# QD 3/17; hydrocortisone 1# q12h 3/18 => QD 3/18 => Prednisolone 3# BID 4/3~9; 1# BID 4/123/18 => Prednisolone 3# BID 4/3~9; 1# BID 4/12
Consult CVS for hickman2/21 => 2/23Consult CVS for hickman2/21 => 2/23 f/u ANCA 2/22; 3/2; 4/5f/u ANCA 2/22; 3/2; 4/5 Lab 3/9 anti-cardiolipin, lupusLab 3/9 anti-cardiolipin, lupus 2/27 2/27 加洗 加洗 dyspnea?dyspnea? PPI 3/14PPI 3/14 3/17 consult GI, ET + MV airway protection3/17 consult GI, ET + MV airway protection
FDL dysfunction => Bilateral deep vein thrombosis => FDL dysfunction => Bilateral deep vein thrombosis => Heparin => Warfarin => refuse Thrombectomy 2/11Heparin => Warfarin => refuse Thrombectomy 2/11
Coaguloapthy Coaguloapthy Pitting edema, hypoalbuminemiaPitting edema, hypoalbuminemia General weakness with black stool=>Channel ulcer General weakness with black stool=>Channel ulcer
bleeding 3/14 bleeding 3/14 Emergent operation for PPU 3/17Emergent operation for PPU 3/17 LMWH for DVT (proven on 3/31) => WarfarinLMWH for DVT (proven on 3/31) => Warfarin Steroid => held due to recurrent UGIBSteroid => held due to recurrent UGIB Follow up C-ANCA => taper steroidFollow up C-ANCA => taper steroid PPI~6/15PPI~6/15 Warfarin + Prednisolon for DVT & Vasculitis => DC Warfarin + Prednisolon for DVT & Vasculitis => DC
warfarin after doppler 2011/07warfarin after doppler 2011/07 Renal biopsy due to anti-anticoagulopathyRenal biopsy due to anti-anticoagulopathy
ConsultationConsultation
1/28 Derma: 1/28 Hema & Rheuma: 1/28 Derma: 1/28 Hema & Rheuma: WengerWenger’’s/Goodpasture related RPGN s/Goodpasture related RPGN dyspnea improve after steroiddyspnea improve after steroid
2/3 Plasty & CVS: acute compartment 2/3 Plasty & CVS: acute compartment syndromesyndromeremove left FDLremove left FDL
DVT on Warfarin; UGIB 3/15 EGDDVT on Warfarin; UGIB 3/15 EGD3/18 GS: gastrostomy and duodenorrhaphy3/18 GS: gastrostomy and duodenorrhaphy
Reddish macula-papula lesions over Reddish macula-papula lesions over bilteral feet bilteral feet