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Research ArticleArticle

A Population-based Study Showing Better Renal Prognosis for Proteinase 3 Antineutrophil Cytoplasmic Antibody (ANCA)–associated Nephritis Versus Myeloperoxidase ANCA–associated Nephritis

Aladdin J. Mohammad and Mårten Segelmark
The Journal of Rheumatology July 2014, 41 (7) 1366-1373; DOI: https://doi.org/10.3899/jrheum.131038
Aladdin J. Mohammad
From the Department of Clinical Sciences, Section of Rheumatology, Lund University; Department of Rheumatology, Skåne University Hospital, Lund; Department of Nephrology UHL, Östergötland County Council; and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
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  • For correspondence: Aladdin.mohammad@med.lu.se
Mårten Segelmark
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  • Figure 1.
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    Figure 1.

    Renal survival by Kaplan-Meier curves according to serology type (139 patients with renal disease at diagnosis; 67 with PR3-ANCA+ and 72 with MPO-ANCA+). PR3: proteinase 3; ANCA: antineutrophil cytoplasmic antibodies; MPO: myeloperoxidase.

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    Figure 2.

    Patient survival by Kaplan-Meier curves according to serology type (183 patients; 98 with PR3-ANCA+ and 85 with MPO-ANCA+). PR3: proteinase 3; ANCA: antineutrophil cytoplasmic antibodies; MPO: myeloperoxidase.

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    Table 1.

    Demographic, laboratory, and clinical characteristics of 183 patients with ANCA-associated vasculitis and ANCA positivity measured by ELISA.

    PR3-ANCA, n = 98MPO-ANCA, n = 85p
    Sex, F/M39/5948/370.024
    Diagnosis: GPA/MPA/EGPA73/25/017/64/4
    Age at diagnosis, yrs63.2 ± 15.968.7 ± 14.40.016
    Diagnosis delay, mos2 (1–4)2 (1–5)0.063
    Laboratory results
      C-reactive protein, mg/dl11.65 (6.5–19.1)3.4 (0.9–12.4)< 0.001
      ESR, mm/h77 ± 3058 ± 350.004
      Hemoglobin, g/dl11.1 ± 1.8210.6 ± 1.770.004
      Thrombocyte count, × 109/l408 (333–517)324 (261–400)< 0.001
      White blood cell count, × 109/l11.9 (9.9–15)9.6 (7.1–13)0.002
      Creatinine, mg/dl1.46 (0.81–3.03)2.67 (1.21–5.19)0.004
    Patients with ≥ 3 organ systems involved, n (%)75 (76)48 (56)0.004
    Deaths during followup, n (%)36 (37)36 (42)0.438
    Organ systems involved at diagnosis
      General, n (%)92 (94)72 (85)0.042
      ENT, n (%)58 (59)16 (19)< 0.001
      Chest, n (%)51 (52)34 (40)0.103
      Nervous, n (%)14 (14)8 (9)0.312
      Cutaneous, n (%)5 (5)6 (7)0.579
      Mucocutaneous and eyes, n (%)10 (10)2 (2)0.032
      Cardiovascular, n (%)4 (4)4 (5)0.837
      Abdominal, n (%)5 (5)8 (9)0.258
      Renal, n (%)67 (68)72 (85)0.01
    • Results are mean ± SD (normally distributed variables) or median and interquartile range (not normally distributed variables), or number and percentage. GPA: granulomatosis with polyangiitis (formerly Wegener); MPA: microscopic polyangiitis; EGPA: eosinophilic granulomatosis with polyangiitis (Churg-Strauss); ENT: ear-nose-throat; ESR: erythrocyte sedimentation rate; ANCA: antineutrophil cytoplasmic antibody; PR3: proteinase 3; MPO: myeloperoxidase.

    • View popup
    Table 2.

    Demographics and laboratory data of 139 patients with AAV and renal involvement.

    PR3-ANCA n = 67MPO-ANCA n = 72p
    Sex, F/M24/4336/360.092
    Diagnosis: GPA/MPA/EGPA42/25/09/62/1
    Age at diagnosis, yrs64.8 ± 16.470.1 ± 14.30.043
    Diagnosis delay, mos2 (1–3)2 (1–4)0.206
    Laboratory results
      C-reactive protein, mg/dl11.8 (8.8–17.7)4.6 (0.9–12.6)< 0.001
      ESR, mm/h80.1 ± 29.664.2 ± 36.00.047
      Hemoglobin, g/dl10.8 ± 1.8910.2 ± 1.680.05
      Thrombocyte count, × 109/l387 (314–483)316 (260–386)0.001
      White blood cell count, × 109/l12.5 (10–15)9.3 (7.1–12.5)0.001
      Creatinine at diagnosis, mg/dl2.64 (1.37–4.10)3.05 (1.73–5.77)0.062
      Creatinine at last followup*, mg/dl1.19 (0.85–1.60)1.39 (1.01–1.84)0.187
    Patients with GFR < 50 ml/min at last followup*, n (%)12/35 (34)13/27 (48)0.243
    Patients developed ESRD, n (%)10 (15)27 (38)0.003
    Patients with ≥ 3 organ systems involved, n (%)50 (75)42 (58)0.042
    Death, n (%)29 (43)35 (49)0.529
    Organ system involved at diagnosis
      General, n (%)64 (96)60 (83)0.021
      ENT, n (%)31 (46)9 (13)< 0.001
      Chest, n (%)32 (48)29 (40)0.374
      Nervous, n (%)7 (10)4 (6)0.286
      Cutaneous, n (%)4 (6)3 (4)0.627
      Mucocutaneous and eyes, n (%)5 (7)1 (1)0.078
      Cardiovascular, n (%)2 (3)3 (4)0.709
      Abdominal, n (%)4 (6)8 (11)0.281
    Renal histology findings, n (%)
      Diffuse crescentic GN, pauciimmune15 (22)11 (15)0.282
      Diffuse crescentic GN, IF not done2 (3)3 (4)0.585
      Diffuse crescentic GN, granular IgG/C31 (1.5)2 (3)0.602
      Focal necrotizing/crescentic GN, pauciimmune24 (36)22 (31)0.509
      Focal necrotizing/crescentic GN, IF not done3 (4.5)8 (11)0.147
      Pauciimmune small vessel vasculitis without GN0 (0)3 (4)0.091
      Miscellaneous or insufficient material for diagnosis5 (8)8 (11)0.46
    No renal biopsy performed17 (25)15 (21)0.525
    • ↵* Data on creatinine and GFR < 50 ml/min at last followup (May 2012), included only patients alive and with native kidney function at last followup. All other demographic, clinical, and laboratory data are based on 139 patients with renal involvement. Results are reported as mean ± SD (normally distributed variables) or median and interquartile range (not normally distributed variables), or number and percentage. AAV: ANCA-associated vasculitis; GPA: granulomatosis with polyangiitis (formerly Wegener); MPA: microscopic polyangiitis; EGPA: eosinophilic granulomatosis with polyangiitis (Churg-Strauss); ESRD: endstage renal disease; ENT: ear-nose-throat; GN: glomerulonephritis; ESR: erythrocyte sedimentation rate; ANCA: anti-neutrophil cytoplasmic antibody; PR3: proteinase 3; MPO: myeloperoxidase; GFR: glomerular filtration rate; IF: immunofluorescence.

    • View popup
    Table 3.

    Risk of endstage renal disease with nephritis.

    HR95% CIp
    MPO+2.641.25–5.580.011
    Age at diagnosis1.010.98–1.030.405
    Sex (male)0.960.68–1.340.815
    S-creatinine3.171.99–5.04< 0.001
    • Cox regression analysis. MPO: myeloperoxidase.

    • View popup
    Table 4.

    Summary of studies on renal and patient survival in patients with AAV based on ANCA serotype (C-/PR3-ANCA and P-/MPO-ANCA).

    Study (reference)YearNo. PatientsRenal InvolvementSpecialtyComparisonCase IdentificationESRDDeath
    Geffriaud-Ricouard, et al1619938392%NephrologyPR3 vs MPOSingle centerNo differenceNo difference
    Franssen, et al1819959275%“Mixed”PR3 vs MPOTeaching hospitalsNo differenceNo difference
    Hogan, et al131996107100%NephrologyC vs P-ANCASpecialized units
    (Glomerular Disease
    Collaborative Network)
    No differenceWorse for C-ANCA
    Westman, et al191998123100%NephrologyPR3 vs MPOSingle centerWorse for PR3#No difference
    Franssen, et al1019989275%“Mixed”PR3 vs MPOTeaching hospitalsNRNo difference
    Vizjak, et al242003135100%“Mixed”PR3 vs MPOSingle centerWorse MPONo difference
    Weidner, et al12200480100%NephrologyPR3 vs MPOSingle centerNo differenceWorse for PR3
    Rihova, et al25200561100%NephrologyC-vs P-ANCASingle centerNo differenceNo difference
    Flossmann, et al262011535100%MixedPR3 vs MPOMulticenter clinical trialsNRWorse for MPO
    Lionaki, et al5201250297%NephrologyPR3 vs MPOSpecialized units
    (Glomerular Disease
    Collaborative Network)
    Worse for MPOWorse for MPO
    de Joode, et al202013212100%NephrologyMPO vs PR3Single centerWorse for MPOWorse for MPO*
    Present study201318376%“Mixed”PR3 vs MPOPopulation-basedWorse for MPONo difference
    • ↵# Analysis with capture ANCA.

    • ↵* Significant difference during the first 6 months after diagnosis. NR: not reported; ESRD: endstage renal disease; ANCA: antineutrophil cytoplasmic antibody; PR3: proteinase 3; MPO: myeloperoxidase.

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1 Jul 2014
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A Population-based Study Showing Better Renal Prognosis for Proteinase 3 Antineutrophil Cytoplasmic Antibody (ANCA)–associated Nephritis Versus Myeloperoxidase ANCA–associated Nephritis
Aladdin J. Mohammad, Mårten Segelmark
The Journal of Rheumatology Jul 2014, 41 (7) 1366-1373; DOI: 10.3899/jrheum.131038

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A Population-based Study Showing Better Renal Prognosis for Proteinase 3 Antineutrophil Cytoplasmic Antibody (ANCA)–associated Nephritis Versus Myeloperoxidase ANCA–associated Nephritis
Aladdin J. Mohammad, Mårten Segelmark
The Journal of Rheumatology Jul 2014, 41 (7) 1366-1373; DOI: 10.3899/jrheum.131038
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Keywords

ANTINEUTROPHIL CYTOPLASMIC ANTIBODY
GLOMERULONEPHRITIS
VASCULITIS
SURVIVAL
ENDSTAGE RENAL DISEASE

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  • ANTINEUTROPHIL CYTOPLASMIC ANTIBODY
  • glomerulonephritis
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  • survival
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