Patients with ANCA-Associated Glomerulonephritis and Connective Tissue Diseases: A Comparative Study from the Maine-Anjou AAV Registry
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Data Collection
2.3. Definitions
2.4. Renal Histopathology
2.5. Statistical Analysis
3. Results
3.1. Baseline Characteristics of Patients of the CTD Group
3.2. Baseline Characteristics of AAV Patients According to the Presence or Absence of CTD
3.3. Comparison of Renal Presentation According to Groups
3.4. Comparison of Outcomes According to Groups
4. Discussion
5. Conclusions
Author Contributions
Conflicts of Interest
References
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Patients (P) | Gender | CTD Diagnosis | Age at CTD | Delay * | CTD-Related Organ Involvement | IS ** | Nature of IS | IS at AAV Onset |
---|---|---|---|---|---|---|---|---|
P1 | Female | RA | 54 | 10 y | Joints | Yes | MTX | No |
P2 | Female | RA | 72 | 2 y | Joints | Yes | Steroids | Yes (steroids) |
P3 | Male | RA | 41 | 8 y | Joints | Yes | Steroids, MTX, anti-TNF | Yes (anti-TNF) |
P4 | Female | RA | 65 | 6 y | Joints | Yes | Steroids, MTX, anti-TNF | Yes (anti-TNF) |
P5 | Female | RA | 35 | 10 y | Joints | Yes | Steroids, MTX, anti-TNF | Yes (anti-TNF) |
P6 | Female | Sarcoidosis | 57 | 9 y | Lung, nodes, salivary glands | Yes | Steroids | No |
P7 | Male | SSc | 71 | 1 y | Skin, Sicca syndrome | No | / | No |
P8 | Female | SSc + SS | 61 | 3 y | Skin, lung, Sicca syndrome | Yes | Steroids | Yes (steroids) |
P9 | Female | SSc + SS | 49 | 6 y | Skin, joints, Raynaud, Sicca syndrome | No | / | No |
P10 | Male | SS | 52 | 25 y | Lung | Yes | Steroids | No |
P11 | Female | SLE | 44 | 5 y | Joints | Yes | Steroids, HCQ | Yes (steroids) |
P12 | Female | PR | 74 | 3 y | Joints | Yes | Steroids, MTX | Yes (steroids+MTX) |
P13 | Female | PR | 60 | 2 y | Joints | Yes | Steroids | Yes (steroids) |
P14 | Female | PR | 74 | 1 y | Joints | Yes | Steroids | Yes (steroids) |
P15 | Male | RP | 60 | 7 y | Joints, ear, nose | Yes | Steroids, MTX | Yes (steroids+MTX) |
P16 | Female | PA | 50 | 14 y | Joints, skin | Yes | Methotrexate | No |
Variables | All, n = 106 | Connective Tissue Diseases | ||
---|---|---|---|---|
Yes, n = 16 | No, n = 90 | p | ||
Baseline characteristics | ||||
Sex (M/F) | 67/39 | 4/12 | 63/27 | 0.001 |
Age (years) | 63.4 ± 14.0 | 65 ± 10.3 | 63.1 ± 14.6 | 0.619 |
ANCA-associated vasculitis characteristics | ||||
Clinical diagnosis, n (%) | ||||
GPA/MPA | 36 (34)/70 (66.6) | 7 (43.7)/9 (56.3) | 29 (32.2)/61 (67.8) | 0.37 |
Newly diagnosed | 98 (92.4) | 15 (93.7) | 83 (92.2) | 0.831 |
ANCA type, n (%) | ||||
c-ANCA/p-ANCA, n (%) | 32 (30.2)/74 (69.8) | 7 (43.7)/9 (56.3) | 25 (27.8)/65 (72.2) | 0.2 |
PR3-ANCA/MPO-ANCA, n (%) | 32 (30.2)/74 (69.8) | 7 (43.7)/9 (56.3) | 25 (27.8)/65 (72.2) | 0.2 |
BVAS at kidney biopsy | 17.3 ± 5.7 | 15.6 ± 5.3 | 17.6 ± 5.8 | 0.2 |
Organ involvement at diagnosis, n (%) | ||||
Cutaneous signs | 20 (18.9) | 3 (18.7) | 17 (18.9) | 1 |
Ear, nose, throat | 34 (32.1) | 6 (37.5) | 28 (31.1) | 0.772 |
Heart | 6 (5.7) | 1 (6.2) | 5 (5.6) | 1 |
Digestive | 4 (3.7) | 1 (6.2) | 3 (3.3) | 0.486 |
Lung | 40 (37.7) | 4 (25) | 36 (40) | 0.401 |
Renal (at kidney biopsy) | - | |||
Serum creatinine, µmol/L | 350.2 ± 296 | 264.7 ± 188 | 364.9 ± 309 | 0.227 |
eGFR, mL/min/1.73 m2 | 32.5 ± 34.7 | 35.0 ± 30.2 | 32.1 ± 35.5 | 0.766 |
Need for renal replacement therapy, n (%) | 13 (12.3) | 0 (0.0) | 13 (15.5) | 0.21 |
Neurological | 14 (13.2) | 2 (12.5) | 12 (13.3) | 0.928 |
Induction therapy, n (%) | ||||
Cyclophosphamide | 97 (91.5) | 14 (87.5) | 83 (92.2) | 0.663 |
Rituximab | 3 (2.8) | 1 (6.2) | 2 (2.2) | - |
Other | 6 (5.7) | 1 (6.2) | 5 (5.5) | - |
Plasma exchange | 31 (29.2) | 5 (31.2) | 26 (28.8) | 0.848 |
Connective Tissue Disease | |||
---|---|---|---|
Yes, n = 16 | No, n = 90 | p | |
Antinuclear antibody | |||
Screened patients, n (%) | 15 (93.7) | 80 (88.8) | 0.556 |
Positives (≥ 1/100), n (%) | 12 (80) | 38 (47.5) | 0.021 |
≥ 1/200, n (%) | 8 (50) | 25 (31.2) | 0.036 |
Antigen specificity, number of patients | 4 | 2 | / |
Anti-SSA, n | 1 | 0 | / |
Anti-SSB, n | 0 | 0 | / |
Anti-centromere, n | 2 | 1 | / |
Anti-mitochondrial, M2 subtype, n | 1 | 1 | / |
Anti-GBM antibody | |||
Screened patients, n (%) | 15 (93.7) | 71 (78.8) | 0.161 |
Positives patients, n (%) | 1 (6.3) | 1 (1.1) | 0.32 |
Cryoglobulin | |||
Screened patients, n (%) | 8 (50) | 35 (38.9) | 0.402 |
Positive, n (%) | 3 (37.5) | 2 (5.7) | 0.011 |
Rheumatoid factor | |||
Screened patients, n (%) | 5 (31.2) | 18 (20) | 0.314 |
Positive, n (%) | 4 (80) | 7 (38.9) | 0.103 |
Immunofluorescence Study | All, n = 106 | Connective Tissue Disease | ||
---|---|---|---|---|
Yes, n = 16 | No, n = 90 | p | ||
IgG deposits | 0.12 ± 0.4 | 0 ± 0 | 0.14 ± 0.5 | 0.24 |
≥2+, n (%) | 2 (1.9) | 0 (0) | 2 (2.2) | 1 |
IgA deposits | 0.14 ± 0.5 | 0 ± 0 | 0.17 ± 0.5 | 0.229 |
≥2+, n (%) | 2 (1.9) | 0 (0) | 2 (2.2) | 1 |
IgM deposits | 0.89 ± 0.5 | 1 ± 0.5 | 0.86 ± 0.5 | 0.343 |
≥2+, n (%) | 7 (6.6) | 2 (12.5) | 5 (5.5) | 0.284 |
C1q deposits | 0.2 ± 0.5 | 0.2 ± 0.4 | 0.17 ± 0.5 | 0.821 |
≥2+, n (%) | 1 (0.9) | 0 (0) | 1 (1.1) | 1 |
C3 deposits | 0.63 ± 0.8 | 0.4 ± 0.7 | 0.67 ± 0.7 | 0.202 |
≥2+, n (%) | 11 (10.4) | 2 (12.5) | 9 (10) | 0.67 |
Variables | All, n = 106 | Connective Tissue Disease | ||
---|---|---|---|---|
Yes, n = 16 | No, n = 90 | p | ||
Relapses, all, n (%) | 23 (21.7) | 6 (37.5) | 17 (18.8) | 0.096 |
Mean delay (months) | 43.6 ± 43.2 | 29.5 ± 30.1 | 46.1 ± 44.8 | 0.158 |
Non-renal relapse, n (%) | 11 (10.4) | 4 (25) | 7 (7.7) | 0.037 |
Mean delay (months) | 35.4 ± 39 | 24.6 ± 34 | 41.6 ± 42.9 | 0.518 |
Renal relapse, n (%) | 12 (11.3) | 2 (12.5) | 10 (11.1) | 1 |
Mean delay (months) | 49.1 ± 37.7 | 35.7 ± 12.3 | 51.7 ± 40.9 | 0.607 |
Steroids | ||||
Steroids at Month 6 | 12.5 ± 8.9 | 12.3 ± 4.9 | 12.5 ± 9.6 | 0.935 |
Steroids at Year 1 | 5.5 ± 5.4 | 4.5 ± 4 | 5.7 ± 5.6 | 0.486 |
Steroids at Year 2 | 3.4 ± 9.5 | 1.93 ± 2.9 | 3.7 ± 10.1 | 0.638 |
Steroid withdrawal | 72 (67.9) | 12 (75.0) | 60 (66.6) | 0.753 |
Mean delay | 18.4 ± 19.1 | 15.7 ± 15.3 | 19.0 ± 19.9 | 0.604 |
Maintenance regimen, n (%) | ||||
Azathioprine | 68 (64.2) | 10 (62.5) | 58 (64.4) | 0.881 |
Rituximab | 33 (31.1) | 6 (37.5) | 27 (30) | 0.55 |
Other | 5 (4.7) | 0 (0) | 5 (5.6) | - |
Events | All, n = 106 | Connective Tissue Disease | ||
---|---|---|---|---|
Yes, n = 16 | No, n = 90 | p | ||
Death, n (%) | 16 (15.1) | 2 (12.5) | 14 (15.5) | 1 |
Mean delay (months) | 32 ± 28.2 | 37.8 ± 13.2 | 31.2 ± 29.8 | 0.767 |
Renal function | ||||
eGFR at year 1, mL/min/1.73 m2 | 42.1 ± 28.4 | 38.8 ± 27.3 | 42.6 ± 28.7 | 0.709 |
eGFR at year 3, mL/min/1.73 m2 | 44.2 ± 32.6 | 55.1 ± 14.6 | 42.9 ± 34.1 | 0.435 |
End-stage renal disease, n (%) | 33 (31.1) | 5 (31.3) | 28 (31.1) | 0.991 |
Mean delay (months) | 19.5 ± 27.4 | 22.6 ± 20.6 | 18.9 ± 28.7 | 0.789 |
Severe infectious events, n (%) | 48 (45.3) | 7 (43.7) | 41 (45.5) | 0.894 |
Mean delay (months) | 23.8 ± 39.1 | 13.7 ± 16 | 25.7 ± 41.9 | 0.461 |
Cardiovascular events, n (%) | 12 (11.3) | 1 (6.25) | 11 (12.2) | 0.688 |
Mean delay (months) | 57.1 ± 56.1 | - | 62.3 ± 55.9 | - |
Myocardial infarction, n (%) | 1 (0.9) | 1 (6.25) | 0 (0) | 0.151 |
Stroke, n (%) | 2 (1.9) | 0 (0) | 2 (2.2) | 1 |
Others, n (%) | 9 (8.5) | 0 (0) | 9 (10) | 0.349 |
Cancer, n (%) | 13 (12.3) | 1 (6.2) | 12 (13.3) | 0.686 |
Mean delay (months) | 40.9 ± 40 | - | 40.9 ± 40 | - |
Solid cancer, n (%) | 6 (5.7) | 0 (0) | 6 (6.7) | 0.588 |
Skin cancer, n (%) | 7 (6.6) | 1 (6.2) | 6 (6.7) | 0.934 |
Thrombotic events, n (%) | 14 (14.2) | 5 (31.2) | 9 (10) | 0.021 |
Mean delay (months) | 47.2 ± 11.9 | 17.1 ± 17.7 | 9.03 ± 16.4 | 0.461 |
At least one event, n (%) * | 66 (62.3) | 11 (68.7) | 55 (61.1) | 0.302 |
Mean follow-up (months) | 55.6 ± 52.2 | 40.6 ± 40.6 | 58.3 ± 53.8 | 0.213 |
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Guibert, F.; Garnier, A.-S.; Wacrenier, S.; Piccoli, G.; Djema, A.; Gansey, R.; Demiselle, J.; Brilland, B.; Cousin, M.; Besson, V.; et al. Patients with ANCA-Associated Glomerulonephritis and Connective Tissue Diseases: A Comparative Study from the Maine-Anjou AAV Registry. J. Clin. Med. 2019, 8, 1218. https://doi.org/10.3390/jcm8081218
Guibert F, Garnier A-S, Wacrenier S, Piccoli G, Djema A, Gansey R, Demiselle J, Brilland B, Cousin M, Besson V, et al. Patients with ANCA-Associated Glomerulonephritis and Connective Tissue Diseases: A Comparative Study from the Maine-Anjou AAV Registry. Journal of Clinical Medicine. 2019; 8(8):1218. https://doi.org/10.3390/jcm8081218
Chicago/Turabian StyleGuibert, Fanny, Anne-Sophie Garnier, Samuel Wacrenier, Giorgina Piccoli, Assia Djema, Renaud Gansey, Julien Demiselle, Benoit Brilland, Maud Cousin, Virginie Besson, and et al. 2019. "Patients with ANCA-Associated Glomerulonephritis and Connective Tissue Diseases: A Comparative Study from the Maine-Anjou AAV Registry" Journal of Clinical Medicine 8, no. 8: 1218. https://doi.org/10.3390/jcm8081218