C- 02 : Thrombotic microangiopathies, HUS
H- 01 : Antibodies and B-cell biology
Clinicopathologic Characteristics and Outcomes of Renal Thrombotic
Microangiopathy in Anti-Neutrophil Cytoplasmic AutoantibodyAssociated Glomerulonephritis
Su-Fang Chen*,†,‡, Huan Wang*,†,‡, Yi-Min Huang*,†,‡, Zhi-Ying Li*,†,‡,
Wang*,†,‡, Feng Yu*,†,‡, Ming-Hui Zhao*,†,‡§, Min Chen*,†,‡
Su-Xia
+ Author Affiliations
*Renal Division, Department of Medicine, Peking University, First Hospital, Beijing, China;
†Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China;
‡Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University,
Ministry of Education, Beijing, China; and
§Peking-Tsinghua Center for Life Sciences, Beijing, China
Correspondence: Dr. Min Chen, Renal Division, Department of Medicine, Peking University, First
Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease, Ministry of
Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking
University), Ministry of Education, Beijing, China. No. 8, Xishiku Street, Xicheng District, Beijing
100034, China. E-mail: chenmin74@sina.com
Journal : CJASN
Year : 2015 / Month : May
Volume : 10
Pages : 750-758
ABSTRACT
Background and objectives
Thrombotic microangiopathy (TMA) in ANCA-associated vasculitis (AAV) has been mainly reported
in isolated case reports. The aim of this study was to analyze clinical and pathologic characteristics
and prognosis of patients with renal TMA in ANCA-associated GN in a large cohort of Chinese
patients.
Design, setting, participants, & measurements
Clinical and renal histopathologic data of 220 patients with biopsy-proven ANCA-associated GN
from 1996 to 2013 were retrospectively analyzed. Patients were followed up for a median period of
32 (interquartile range [IQR], 12–65) months, and outcomes of patients were analyzed.
Results
Among the 220 patients with ANCA-associated GN, 30 were identified having concomitant renal
TMA by pathologic evaluation. Compared with the non-TMA group, patients with renal TMA
presented with more severe renal injury, as evidenced clinically by a higher level of serum creatinine
at diagnosis (5.0 [IQR, 3.5–9.0] versus 3.2 [IQR, 1.7–6.8] mg/dl; P=0.02) and pathologically by a
higher percentage of cellular crescents (15.0% [IQR, 6.9%–34.9%] versus 6.9% [IQR, 0%–21.1%];
P=0.04) and more severe interstitial infiltration (2 [IQR, 2–2] versus 2 [IQR, 1–2]; P=0.03) in renal
biopsies. Furthermore, multivariate analysis showed that renal TMA was independently associated
with mortality of patients with AAV after adjusting for age, sex, initial serum creatinine, tubular
atrophy, and interstitial fibrosis (hazard ratio, 1.92; 95% confidence interval, 1.08 to 3.41; P=0.03) or
for age, sex, the histopathologic classification scheme proposed by Berden et al. (J Am Soc Nephrol
21: 1628–1636, 2010), tubular atrophy, and interstitial fibrosis (hazard ratio, 1.95; 95% confidence
interval, 1.07 to 3.55; P=0.03).
Conclusions
Renal TMA in ANCA-associated GN is not rare and presents with more severe renal injury. Renal
TMA is independently associated with all-cause mortality in patients with AAV.
Key words : ANCA, vasculitis, thrombosis, outcomes
COMMENTS
ANCA-associated vasculitis (AAV) is a group of systemic autoimmune diseases characterized by
pauci-immune necrotizing small-vessel vasculitis and circulating autoantibodies against neutrophil
cytoplasmic constituents, especially proteinase 3 and myeloperoxidase. AAV comprises
granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis
with polyangiitis (EGPA), and renal-limited vasculitis (RLV).
Thrombotic microangiopathy (TMA) comprises a group of clinical and pathologic syndromes that
share a similar pathologic process, characterized by endothelial and blood cell damage and
thrombotic microvascular occlusions. TMA comprises a spectrum of distinct disorders, including
typical and atypical hemolytic uremic syndrome (HUS), congenital and acquired thrombotic
thrombocytopenic purpura, malignant hypertension, pregnancy, organ transplantation, drugs, or
systemic autoimmune diseases. Renal involvement is common in TMA.
The aim of this study was to analyze clinical and pathologic characteristics and the prognosis of
patients with renal TMA in ANCA-associated GN in a large cohort of Chinese patients.
A total of 220 consecutive patients with ANCA-associated GN who received renal biopsy, diagnosed
in the Department of Nephrology, Peking University First Hospital from 1996 to 2013, were analyzed
retrospectively. Renal biopsy was performed at the time of diagnosis and before the initiation of
immunosuppressive therapy. All patients met the criteria of the 2012 Chapel Hill Consensus
Conference definition for AAV. Known causes of renal TMA, including SLE, anti-phospholipid
syndrome, scleroderma, pregnancy-associated TMA, malignant hypertension, transplantationassociated TMA, disseminated intravascular coagulation, drug-mediated TMA, and TMA associated
with various infections, including HIV, hepatitis B virus, and hepatitis C virus, were excluded.
ANCA tests were performed by both indirect immunofluorescence assay and antigen-specific ELISA
for all patients at the time of presentation and before immunosuppressive treatment was instituted,
according to the manufacturer’s instruction (Euroimmun, Lübeck, Germany).
None of the patients with renal TMA in our study presented with a congenital deficiency of serum
ADAMTS-13 activity, with a median activity of 98.6% (range, 97.1%–99.6%).
The induction therapy included corticosteroids in combination with cyclophosphamide. Patients with
ARF or pulmonary hemorrhage received three pulses of intravenous methylprednisolone before the
standard induction therapy. Patients with severe pulmonary hemorrhage additionally received
plasma exchanges. For maintenance therapy, intravenous cyclophosphamide every 3 months or
daily oral azathioprine was given, with a duration of at least 2 years.
Patients were followed-up on for a median period of 32 (IQR, 12–65) months. Six out of 30 (20.0%)
patients with renal TMA and 57 out of 190 (30.0%) patients without renal TMA experienced a
disease relapse, respectively.
Multivariate analysis revealed that renal TMA was an independent risk factor for patients’ survival
after adjusting for age, sex, initial serum creatinine, interstitial fibrosis, and tubular atrophy.
In conclusion, renal TMA in ANCA-associated GN is not rare, and it presents with more severe renal
injury. Renal TMA is independently associated with all-cause mortality of patients with AAV.
Pr. Jacques CHANARD
Professor of Nephrology