Rapidly Progressive Lupus Nephritis with Extremely High Levels of Antineutrophil Cytoplasmic Antibodies
A 43-year-old Caucasian woman was admitted to the hospital due to acute renal failure and proteinuria in the nephrotic range. She presented with a 3-month history of fatigue, anaemia and lymphadenopathy. Before admission, a CT scan was performed, which revealed lymphadenopathy of the neck as well as generalized abdominal and mediastinal lymphadenopathy. Lymph node excision showed reactive lymphadenopathy. No history of skin rashes, photosensitivity, joint swelling, hair loss or oral ulcers was identified. On physical examination, the patient's height was 170 cm, her weight 56 kg (BMI 19.4), she was afebrile and her blood pressure was 117/77 mm Hg.\nLaboratory examinations revealed (table ) a white blood cell count of 3.2 × 109/l (reference range, 4–10 × 109/l), lymphocytes 13.5% (reference range, 10–50%), haemoglobin 102 g/l (reference range, 115–165 g/l), platelets 147 × 109/l (reference range, 150–350 × 109/l), total protein 71 g/l (reference range, 64–83 g/l), albumin 27 g/l (reference range, 35–50 g/l), lactate dehydrogenase 161 U/l (reference range, <250 U/l), haptoglobulin 1.85 g/l (reference range, 0.3–2.0 g/l), urea 12.6 mmol/l (reference range, 2.7–6.8 mmol/l), creatinine 174 μmol/l (reference range, 45–84 μmol/l), C-reactive protein <5 mg/l (reference range, <5 mg/l) and an increased erythrocyte sedimentation rate of 81 mm/h. Urine analysis showed proteinuria of 6.4 g/day and an active sediment containing dysmorphed red blood cells. Serum complement levels were low with a C3c of 0.2 g/l (reference range, 0.8–1.8 g/l), C4 0.02 g/l (reference range, 0.1–0.4 g/l), and CH50 14 U Eq/ml (reference range, 70–180 U Eq/ml). Antinuclear antibodies were elevated to 1:80 (reference range, <40-fold), anti-double-stranded DNA antibodies were not detectable and anti-C1q was 20 IU/ml (reference range, <15 U/ml). ANCA titres on immunofluorescence were increased up to 1:640 (reference range <1:20). Using enzyme-linked immunosorbent assay (ELISA), MPO-ANCAs were positive with 3,622 U/ml (reference range, <5 U/ml) and PR3-ANCAs were not detectable. Anti-SS-A/Ro52 were 22 U/ml (reference range, <10 U/ml) and anti-SS-A/Ro60 were >240 U/ml (reference range, <10 U/ml). Cryoglobulines were not detectable. Serologic tests for HIV, hepatitis B/C and cytomegalovirus were all negative. Epstein-Barr-virus IgG was positive, IgM was negative and EBNA1 IgG was positive.\nRenal biopsy was performed on day 2, which revealed a diffuse, segmental, proliferative, immune-complex GN with crescents in 4 of 19 glomeruli corresponding to an LN class IV-S (A/C; fig. ). Immunofluorescence staining showed deposition of IgA, IgM, C1q, C3 and C5–9 in the mesangial area and peripheral capillaries. Electron microscopy revealed mesangial and peripheral electron-dense deposits without obvious structuring. Most of the peripheral deposits were located subendothelially, there were also some subepithelial deposits. Tubulo-reticular structures within one endothelial cell were found.\nAfter renal biopsy, methylprednisolone pulses were initiated (500 mg/day for 3 days) followed by oral prednisone 50 mg/day and cyclophosphamide 1 g intravenously. However, the serum concentration of creatinine gradually increased, so that again methylprednisolone pulses (500 mg/day for 2 days) were repeated on day 13, and high volume plasma exchange was started for 5 consecutive days to eliminate MPO-ANCAs (fig. ). After the plasma exchanges, the MPO-ANCA levels were decreased to 104 U/l and renal function improved so that the patient was discharged on day 39. Cyclophosphamide therapy was continued with 500 mg intravenously every second week for 3 months, so that the patient received a cumulative dose of 3.5 g. The maintenance therapy with azathioprine had to be switched to mycophenolate mofetil due to gastrointestinal side effects. Eighteen months after starting treatment, the patient is still in remission. MPO-ANCAs are not detectable and renal function has recovered completely with a creatinine concentration of 88 μmol/l (reference range, 45–84 μmol/l) and a minimal proteinuria of 0.2 g/day – using a treatment regime consisting of mycophenolate mofetil 2 g, prednisone 7.5 mg and hydroxychloroquine 200 mg per day.