ANCA vasculitis and Renal Diseases

ANCA vasculitis and Renal diseases
PRESENTED BY
Dr.C.MALSAWMKIMA
DM NEPHROLOGY STUDENT
DEPT. OF NEPHROLOGY
AIIMS JODHPUR
Date: 04-07-2020

 Name - Mr. MR
 Age/ sex - 70 yr/ m
 Address -Punasa, Jalore, Rajasthan
 Occupation - Farmer
 AIIMS ID - 2018/06/011787
 DOA - 10/07/2019
 DOD - 23/07/2019
 Department - Nephrology

 Bilateral LL swelling x 7 days
 Facial puffiness x 7 days
 Decreased urine output x 7 days

Past history
 BCC over nose for past 6 months
 Not k/c/o DM/HTN/CAD
 No h/o surgery/ Blood Tx
Personal history
 Non-smoker/Non-alcoholic/No Drug abuse
Family history
 Not significant

 Conscious, oriented
 Vitals
 PR 96/min, regular, good volume
no arterial wall thickening,
all peripheral pulses palpable
 RR 18/min
 Afebrile
 BP 140/80
 SpO₂ 98% RA
 Pallor +
 Icterus-
 Clubbbing -
 Cyanosis -
 LNP -
 Pedal edema +
 Facial puffiness+
 Purpuric spots over
chest and LL

 CVS
 R/S WNL
 P/A
 CNS

10/7/19 27/7/19
Hb 4.9 7.5
TLC 12 7.3
Plts X 10ᵌ 256 112
Hemogram
10/7/19 21/7/19
Na/K 142/3.7 136/3.9
U/Cr 205/6.8 82/2.0
T.Bil 0.4
SGOT/PT 37/26
ALP 166
Prot/Alb 7.7/2.8
Ca/Phos/UA 8.7/9.9/10
Iron/TIBC/Ferritin 20/271/-
Biochemistry
Coagulogram
10/7/19
PT 14.6
INR 1.2
aPTT 27

 USG KUB: RK-9.1 cm, LK- 9.2cm, increased cortical
echogenicity
 ECG and CXR
 Normal
 Urine r/m/e
 Protein 3+
Sugar-nil
RBC-full field/hpf
 24 hr Urine protein
 1.4 g/d

 P-ANCA- positive
 C3-low, C4-normal
 ANA-negative
 HbA1C-5.3%
 HIV-NR
 Anti HCV-NR
 HBsAg-NR
 Stool OBT-negative

 Renal biopsy:
(A) shows a low power view of renal parenchyma displaying 5 glomeruli in
the field, two of which are showing cellular crescents (PAS 100X). (B) is
the high-power view displaying a cellular crescent with focal fibrinoid
necrosis of the tuft. The underlying tuft is otherwise unremarkable, no
capillary wall thickening is identified.

70 yr/M, with background h/o BCC,
presented with decreased U.O, pedal
edema and facial puffiness for 1 week
Examination revealed pallor, pedal
edema and facial puffiness, purpuric
lesions over chest and LL, BCC over
nose
Lab parameters revealed severe IDA,
micro-hematuria, sub-nephrotic range
proteinuria and normal size kidneys,
impaired KFT

P-ANCA was positive
Low C3
Renal Biopsy showed f/s/o Necrotizing
and crescentic GN (NCGN)
Diagnosis of ANCA associated NCGN
was made

Managed with
1.IVMP 500 mg iv OD x 3 days f/b oral
Pred 1mg/kg/d
2.IV CYC 0.5 g/m2 monthly (received 2
doses)
3.PLEX x 7 sessions on A/D
Additional therapy
1.Antihypertensive
(NICARDIA+MET XL)
2.SHELCAL + SEPTRAN DS EOD+
RANTAC
3.PRBC x 3Tx + oral IRON

Outcome on follow up
Creatinine declined from 2.0 ,g/dl at
discharge to 1.3mg/dl at last follow up
(around 2 weeks after 2rd dose of CYC)
Before subsequent follow up, the
patient died at home for unclear
reason

Overview of ANCA associated renal disease
 Introduction and historical landmarks
 Definition
 Pathogenesis
 Clinical features
 Diagnosis
 Histopathological classification
 Approach and Treatment
 Relapse and refractory
 Role of PLEX
 Special conditions

 AAV is a small vessel vasculitis
 Small vessel vasculitis is a necrotizing vasculitis with few or
no immune deposits
 Affects capillaries, arterioles and venules , sometimes small
arteries
 Most common renal target is glom. capillaries, and hence GN
is the most common renal clinical manifestation

 Systemic vasculitis associated with autoantibodies to neutrophil
cytoplasmic antigens (ANCA) is the most frequent cause of
rapidly progressive glomerulonephritis
 Renal failure at presentation carries an increased risk for ESRD
and death despite immunosuppressive therapy
 Usually begins at 5th ,6th , 7th decades and peak at 65-75 years of
age; but may occur at any age
 Around 90% of small vessel vasculitis or NCGN have positive
ANCA (MPO or PR3)

Clin J Am Soc Nephrol 2017;12: 1680–91

MPO-ANCA PR3-ANCA
Ethnicity More in Asian/Indian,
southern Europe, southern
USA
More in northern Europe and
USA
HLA DQ DP
Organ More renal More pulmonary/ENT
Pathology More sclerosis More necrosis,
More granulomatous
inflammation
Anti-GBM
association
5% of AAV has anti-GBM+,
35% of all Anti-GBM disease
has MPO-ANCA
0
Relapse Lesser More
ESRD, Death Lesser More

Clin J Am Soc Nephrol 2017;12: 1680–91Clin J Am Soc Nephrol 2017;12: 1680–91

 Microscopic hematuria with dysmorphic RBCs and red cell
casts
 Proteinuria- moderate (1-3 g/d)
 RPGN
 AKI/ Pulmonary-renal syndrome
 Renal failure
#Pauci-immune focal and segmental necrotizing and crescentic
GN (NCGN)
# mainly in GPA and MPA, rare with EGPA

 ANCAs in other small-vessel vasculitides:
 30–38% of patients with EGPA- a disease characterized by
asthma, eosinophilia and granulomatous inflammation
 20–35% of patients with anti-glomerular basement
membrane (anti-GBM) disease
 The majority of these ANCA-positive patients have MPO-
ANCAs

 ANCAs in gastrointestinal disorders:
 IBD(Ulcerative colitis (50–67%), Crohn’s disease (6–15%)
 Primary sclerosing cholangitis
 Inflammatory liver diseases (such as autoimmune hepatitis,
primary biliary cirrhosis and chronic viral hepatitis)
 Slightly aberrant P-ANCA pattern that is often referred to as
atypical P-ANCA or X-ANCA

 ANCAs in systemic inflammatory and malignant diseases:
 Reported in rheumatoid arthritis and systemic lupus
erythematosus
 A rare association of AAV with malignant haemopathy (mainly
non-Hodgkin lymphoma and myelodysplasia)
 ANCAs and infection:
 Infective endocarditis can mimic ANCA-associated
glomerulonephritis (both MPO and PR3-ANCA can+)

 Drug-induced AAV: can cause secondary forms of AAV
 Levamisole-adulterated cocaine
 Hydralazine
 Propylthiouracil
 Minocycline

 In a series of 30 patients with AAV associated with cocaine
use, all patients had MPO-ANCA and 50% had PR3-ANCAs.
Double positivity for MPO-ANCAs and PR3-ANCAs is a
characteristic of this disease
 Hydralazine-induced AAV- MPO-ANCAs can be found
together with HNE-ANCAs, lactoferrin-ANCAs and ANAs
#HNE-ANCAs=human neutrophil elastase -ANCAs

 Propylthiouracil- high titres of MPO-ANCAs are usually
found. 32–41% of propylthiouracil-treated patients develop
ANCAs (PR3-ANCAs and HNE-ANCAs)
 Minocycline-P-ANCA in~80% of individuals
 Taken together, most patients with drug-induced AAV have
MPO-ANCA, which can be found in combination with
antibodies to other neutrophil cytoplasmic proteins and ANAs

 Segmental fibrinoid necrosis/ necrotizing GN/Crescentic GN
 Leukocyte infiltration and leukocytoclasia
 Neutrophil infiltration (earliest vasculitic lesion) is replaced
quickly by mononuclear leukocytes
 Necrotizing lesion evolve into sclerotic lesions

J Am Soc Nephrol 2010;21: 1628–1636

J Am Soc Nephrol 2010;21: 1628–1636
5 year renal survival
93%
76%
61%
50%
5 year

Induction
Maintenance
Plasmapheresis

 Low dose SMX/TMP or other alternative for PCP prophylaxis
 Duration- for duration of CYC or 6 months following Rituximab
infusions (KDIGO 2020)

N Engl J Med 2010;363:221-32
RAVE

N Engl J Med 2010;363:211-20
RITUXVAS

 Initial IVMP (1-3g in total) in more severe presentation
 Then, Prednisolone 1mg/kg/d x 1week followed by
programmed tapering
 Target Pred 5mg/d by 6th month following CYC induction,
and Pred withdrawal by 6th month in Ritux induction

Kidney International (2019) 95, 281–295

IgG level should be done at baseline, and every 6 months in patient treated
with RTX ; low level ( < 3 g/L) predicts greater secondary immunodeficiency

N Engl J Med 2010;363:221-32.
RAVE

J Am Soc Nephrol 2007;18: 2180–88
24% reduced risk of progression to ESRD at 1 year

N Engl J Med 2020; 382:622-631

 MEPEX trial showed improved kidney outcomes in patients with
severe kidney disease (SCr > 500 μmol/l) who were treated with
plasma exchange
 Meta-analysis showed a reduction in the occurrence of ESKD at
3 and 12 months after diagnosis
 PEXIVAS trial failed to demonstrate that plasma exchange
delayed the time to ESKD or death for AAV patients presenting
with GFR <50 ml/min/1.73 m2 or alveolar hemorrhage over a
median follow-up of 2.9 years

 Post hoc studies of the PEXIVAS dataset and meta-analysis may
generate results relevant to future recommendations
 Routine use of PLEX is not recommended for patients presenting
with a GFR <50 ml/min/1.73 m2
 But plasma exchange can be considered in those with more
severe presentations (SCr >500 μmol/l, especially if oliguric) or
in those with alveolar hemorrhage and hypoxemia in whom early
mortality is high

 DAH
 ANCA+AntiGBM
 ANCA in LN

Kidney International 2017; 92, 693–702

Kidney International 2017; 92, 1223–31

 Acovaptan vs Glucocorticoid induction therapy in
combination with CYC or RTX
 Results awaited

ANCA vasculitis and Renal Diseases

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