Clinicopathologic characteristics and outcomes of renal thrombotic microangiopathy in anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis

Clin J Am Soc Nephrol. 2015 May 7;10(5):750-8. doi: 10.2215/CJN.07910814. Epub 2015 Mar 6.

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.

Keywords: ANCA; outcomes; thrombosis; vasculitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / blood
  • ADAMTS13 Protein
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Anti-Inflammatory Agents / therapeutic use
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / complications
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / mortality
  • Antibodies, Antineutrophil Cytoplasmic / analysis
  • Azathioprine / therapeutic use
  • Creatinine / blood
  • Cyclophosphamide / therapeutic use
  • Female
  • Glomerulonephritis / complications*
  • Glomerulonephritis / drug therapy
  • Glomerulonephritis / immunology
  • Glomerulonephritis / pathology*
  • Hemoglobins / metabolism
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Methylprednisolone / therapeutic use
  • Middle Aged
  • Prognosis
  • Recurrence
  • Retrospective Studies
  • Severity of Illness Index
  • Survival Rate
  • Thrombotic Microangiopathies / complications*
  • Thrombotic Microangiopathies / drug therapy
  • Thrombotic Microangiopathies / mortality
  • Thrombotic Microangiopathies / pathology*
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents
  • Antibodies, Antineutrophil Cytoplasmic
  • Hemoglobins
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Creatinine
  • ADAM Proteins
  • ADAMTS13 Protein
  • ADAMTS13 protein, human
  • Azathioprine
  • Methylprednisolone