Key messages
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Kidney involvement in HUV can be life-threatening and lead to end-stage kidney disease.
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Glomerular, vascular and tubulo-interstitial compartments can be injured, with frequent C1q deposits.
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Systematic screening for kidney involvement during flares of HUV could accelerate diagnosis and treatment and reduce kidney damage.
Introduction
Patients and methods
Results
Patients’ characteristics
Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 | Patient 10 | Patient 11 | Patient 12 | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Age at kidney involvement | 42 | 12 | 41 | 40 | 41 | 5 | 44 | 56 | 55 | 76 | 45 | 43 |
Gender | F | F | F | F | F | M | F | F | F | M | F | F |
Extra-renal involvement | ||||||||||||
Asthenia/fever | +/+ | +/+ | +/− | +/− | +/− | −/+ | +/− | −/− | −/− | +/+ | +/+ | +/− |
Chronic urticaria | + | + | + | + | + | + | + | + | + | + | + | + |
Angioedema/purpura/livedo | −/+/+ | −/−/− | −/+/− | +/−/− | +/−/− | −/−/− | +/−/− | −/−/− | +/−/− | −/+/− | −/−/− | −/−/− |
Cutaneous leucocytoclastic vasculitis | + | – | + | + | + | ND | – | + | ND | + | ND | + |
Arthralgia/arthritis | +/+ | +/+ | +/− | −/− | +/+ | −/− | +/− | −/− | +/− | +/− | −/− | +/− |
Anterior uveitis/conjunctivitis | +/+ | −/+ | −/− | −/− | +/− | −/− | −/− | −/− | −/− | −/− | −/− | +/− |
Retinopathy | + | – | – | – | – | – | – | + | – | – | – | – |
Lymphadenopathy | + | – | – | – | + | – | + | – | + | – | – | + |
PRESS/peripheral neuropathy | +/− | +/− | −/− | −/− | −/− | −/− | −/− | −/− | −/− | −/− | −/− | −/− |
Respiratory disease | – | + | – | + | – | – | – | + | – | – | – | – |
Pericarditis | + | – | – | – | – | – | – | – | – | – | – | – |
Renal presentation | ||||||||||||
Time since first symptoms of HUV (months) | 84 | 22 | 37 | 55 | 49 | 42 | 60 | 0,5 | 36 | 76 | 0 | 6 |
Proteinuria | + | + | + | + | + | + | + | + | + | + | + | + |
Nephrotic syndrome | + | – | + | + | – | + | + | – | + | – | – | – |
Microscopic/macroscopic haematuria | +/− | −/− | +/+ | +/+ | −/− | +/+ | +/+ | +/− | +/+ | +/− | −/− | +/− |
Serum creatinine (μmol/L) | 225 | 703 | 325 | 90 | 71 | ND | 160 | 77 | 326 | 608 | 268 | 140 |
AKI | + | + | + | – | – | – | + | – | + | + | + | + |
Hemodialysis at diagnosis | – | + | – | – | – | – | – | – | – | + | – | – |
High blood pressure | + | + | – | – | – | – | + | + | + | + | – | + |
Pathological diagnosis | MPGN | MPGN | MPGN | MPGN | MPGN | MPGN | MPGN | MPGN | PI CGN | PI CGN | NV | IN |
Biology | ||||||||||||
Elevated CRP | + | ND | ND | ND | ND | ND | ND | – | + | + | + | + |
Low C3 | + | + | + | + | + | + | + | + | ND | + | ND | + |
Low C4 | + | + | + | + | + | + | + | + | + | + | ND | + |
Low CH50 | + | + | + | + | + | + | ND | + | ND | + | ND | + |
Low C1q | + | + | + | ND | + | ND | ND | ND | + | + | ND | + |
Anti-C1q antibody | + | ND | + | – | + | ND | + | + | + | – | + | + |
Antinuclear antibody | – | + | – | + | – | – | + | + | + | – | + | + |
Antiphospholipid antibody | – | – | ND | – | ND | ND | ND | ND | ND | – | + | ND |
Rheumatoid factor | + | – | – | – | – | – | – | ND | ND | – | – | + |
Cryoglobulinemia | + | – | – | – | – | – | + | + | ND | + | – | + |
ANCA (anti-MPO/anti-PR3) | – | + (+/−) | – | – | – | – | + (+/−) | + (−/+) | + (+/−) | – | + (−/−) | + (−/−) |
Monoclonal gammapathy | – | – | – | – | – | – | – | – | – | + | – | – |
Renal involvement of HUV
Patient 1 | Patient 2 (2003) | Patient 2 (2008) | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 (2012) | Patient 7 (2016) | Patient 8 | Patient 9 (2018) | Patient 9 (2021) | Patient 10 | Patient 11 | Patient 12 | |
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Pathological diagnosis | MPGN | MPGN | MPGN | MPGN | MPGN | MPGN | MPGN | MPGN | MPGN | MPGN | Pauci-immune CGN | Advanced chronic lesions | Pauci-immune CGN | Necrotizing vasculitis | Interstitial nephritis |
Number of glomeruli | 21 | 7 | 13 | 12 | 22 | 11 | 45 | 13 | 16 | 9 | 21 | 18 | 22 | 10 | 14 |
Endocapillary hypercellularity | severe | mild | mild | mild | moderate | mild | moderate | mild | mild | moderate | – | – | – | – | – |
Crescents (% of glomeruli) | 30 | 15 | – | – | 15 | – | 10 | – | 5 | – | 40 | – | 15 | – | – |
Glomerular sclerosis (%) | 30 | – | 30 | – | – | – | – | 60 | 60 | – | 15 | > 90 | 20 | – | 15 |
Subendothelial deposits | IgG+++ C3+/− | IgG+ IgM+/− C3+/− C1q+ | IgG+ C3+ | IgG++ IgM++ C3+++ C4++ C1q+++ | IgG+ IgM+ C3++ C4+ C1q++ | IgA+ IgG+ IgM+ C1q + | IgG++ C3+++ | IgG+ IgM+ C3+++ C1q++ | IgM++ C3++ C1q+ | IgA+ IgG++ IgM+/− C3+/− C1q +/− | IgA+ | – | – | – | – |
Micro thrombi | + | – | – | + | + | – | – | – | – | – | – | – | – | – | – |
Interstitial inflammation | severe | severe | mild | severe | mild | mild | mild | severe | severe | moderate | moderate | – | moderate | severe | moderate |
Interstitial fibrosis | mild | – | moderate | – | – | mild | – | severe | severe | moderate | moderate | severe | mild | – | mild |
Tubular immune deposits | – | IgG+ C1q+ | – | – | C1q++ | – | – | – | – | IgG++ | IgG+++ IgM+ C3+ C1q+ | IgA + IgG+++ IgM+ C3+ | – | – | IgG+/− C1q+/− |
Necroziting vasculitis | – | + | – | – | – | – | – | – | – | – | – | – | – | ++ | – |
Chronic vascular lesions | – | + | + | – | + | + | – | + | + | + | + | + | + | + | + |
Vascular Immune deposits | – | IgG+++ IgM+ C3+ C1q++ | IgG++ IgM++ C3+ C1q+ | – | C1q+ | – | – | – | – | – | IgG+++ IgM+ C3+ C1q+ | IgA + IgG+++ IgM+ C3+ | C3+ | C3+/− | C3+ |
Treatment and outcome
Kidney involvement of HUV in the literature
Patients report | Litterature review | p | Total | |
---|---|---|---|---|
Number of patients | 12 | 26 | 38 | |
Age at diagnosis (years), mean | 42 | 32 | 0.14 | 35 |
Female gender, n (%) | 9 (75%) | 16 (61%) | 0.49 | 25 (66%) |
Clinical examination | ||||
Asthenia/fever | 10 (83%) | 13 (50%) | 0.07 | 23 (60%) |
Chronic urticaria | 12 (100%) | 26 (100%) | 1 | 38 (100%) |
Angioedema/purpura/livedo | 7 (58%) | 13 (50%) | 0.73 | 20 (53%) |
Cutaneous leucocytoclastic vasculitis | 7/9 (78%) | 18/18 (100%) | 0.1 | 25/27 (92%) |
Arthralgia/arthritis | 8 (67%) | 13 (50%) | 0.49 | 21 (55%) |
Anterior uveitis/conjunctivitis | 4 (33%) | 8 (30%) | 1 | 12 (32%) |
Retinopathy | 2 (17%) | 1 (3%) | 0.23 | 3 (8%) |
Lymphadenopathy | 5 (42%) | 5 (19%) | 0.23 | 10 (26%) |
PRESS/peripheral neuropathy | 2 (17%) | 2 (7%) | 0.58 | 4 (11%) |
Abdominal pain | 1 (8%) | 10 (38%) | 0.12 | 11 (29%) |
Respiratory disease | 3 (25%) | 5 (19%) | 0.69 | 8 (21%) |
Cardiac involvement | 1 (8%) | 3 (11%) | 1 | 4 (11%) |
Renal presentation | ||||
Proteinuria | 12 (100%) | 22 (84%) | 0.29 | 34 (89%) |
Nephrotic syndrom | 6 (50%) | 7 (26%) | 0.27 | 13 (34%) |
Microscopic/macroscopic hematuria | 9 (75%) | 17 (65%) | 0.71 | 26 (68%) |
Acute kidney injury | 8 (67%) | 10 (38%) | 0.16 | 18 (47%) |
Hemodialysis at diagnosis | 2 (17%) | 1 (3%) | 0.23 | 3 (8%) |
High blood pressure | 7 (58%) | 3 (11%) | 0.005 | 9 (24%) |
Biology | ||||
Elevated CRP, fibrinogen or ESR | 5 (42%) | 10 (38%) | 1 | 15 (39%) |
Low C3 | 10 (83%) | 23 (88%) | 0.64 | 32 (84%) |
Low C4 | 11 (92%) | 21 (80%) | 0.64 | 31 (82%) |
Low CH50 | 9 (75%) | 14 (53%) | 0.29 | 22 (58%) |
Low C1q | 7 (58%) | 10 (38%) | 0.31 | 17 (45%) |
AntiC1q antibody | 8 (67%) | 10 (38%) | 0.16 | 17 (45%) |
Antinuclear antibody | 7 (58%) | 8 (30%) | 0.16 | 14 (37%) |
Antiphospholipid antibody | 1 (8%) | 1 (3%) | 0.54 | 2 (5%) |
Rheumatoid factor | 2 (17%) | 2 (7%) | 0.58 | 4 (11%) |
Cryoglobulinemia | 5 (42%) | 0 | 0.002 | 3 (8%) |
ANCA | 6 (50%) | 3 (11%) | 0.02 | 8 (21%) |
Monoclonal gammopathy | 1 (8%) | 0 | 0.32 | 1 (3%) |
Renal biopsy | ||||
Membranoproliferative GN | 8 (67%) | 15 (57%) | 0.73 | 23 (61%) |
Membranous nephritis | 0 | 3 (11%) | 0.54 | 3 (8%) |
Lupus like GN (diffuse deposits only) | 0 | 5 (19%) | 0.16 | 5 (13%) |
Crescentic GN/vasculitis | 3 (25%) | 2 (7%) | 0.30 | 5 (13%) |
Interstitial nephritis | 1 (8%) | 1 (3%) | 0.54 | 2 (5%) |
Mean duration of follow up (months) | 107 | 44 | 0.002 | 71 |
Deceased | 0 | 5 (19%) | 0.16 | 5 (13%) |
End-stage kidney disease | 4 (33%) | 4 (15%) | 0.23 | 8 (21%) |
Transplantation/Dialysis | 1 (8%)/2 (17%) | 1 (3%)/3 (11%) | 0.54/0.54 | 2 (5%)/5 (13%) |
eGFR: 15-60 ml/min/1.73 m2 | 2 (17%) | 3 (11%) | 0.64 | 5 (13%) |
Persistant proteinuria (> 0.3 g/24 h or g/g) | 4 (33%) | 4 (15%) | 0.23 | 8 (21%) |