Case report
A 29-year-old Chinese female without prior history or family history of kidney disease presented with eyelid edema for more than one year. She did not have skin rash, arthralgia, photosensitivity, or oral ulcers. During her pregnancy 5 months prior, she was found to have proteinuria on urinalysis. At the current admission, the patient’s initial blood pressure and pulse rate were 166/100 mmHg and 110 beats/min, respectively. She did not have fever (36.6°C), and had an intact mental status. Laboratory results revealed a normal leukocyte count (6.9 × 109/L) with 81.3% neutrophils, anemia (hemoglobin 70 g/L), mild thrombocytopenia (130 × 109/L), hypoalbuminemia (26.2 g/L), normal lactate dehydrogenase (LDH) (391.2 U/L), creatinine (119.3μmol/L), and uric acid (616.4 μmol/L), and hyperlipidemia (total cholesterol 7.72 mmol/L). Her serum β2-microglobulin was 10.07 mg/L. Daily urinary protein was 3.270 g. Her C3 and C4 levels were 1.17 g/L (reference range, 0.7–1.4 g/L) and 1.16 g/L (reference range, 0.1–0.4 g/L), respectively, with a d-dimer of 4.83 μg/mL. Her ANA, anti-double strand DNA antibody, lupus anticoagulant, anticardiolipin antibody, and Coombs’ test were all negative. Computed tomography of her chest and abdomen revealed moderate bilateral pleural effusion with partial atelectasis or consolidation of adjacent lung tissues, massive peritoneal and pelvic effusion, massive pericardium effusion, and extensive subcutaneous soft tissue swelling and effusion involving her chest and abdominal wall (Fig1 A). Since admission, her hemoglobin ,platelet,LDH levels showed gradual decline. The presence of red blood cell fragmentation was observed. Despite component therapy, her hemoglobin levels fluctuated between 57 and 72 g/L, and her platelet levels decreased from 130 × 109/L to 66 × 109/L. 3% red blood cell fragmentation, Serum disintegrin, metalloproteinase with thrombospondin motifs 13 (ADAMTS13), and human complement factor H levels were checked and the results were all within normal range.
Subsequently, a kidney biopsy was performed. Under light microscopy, 26 glomeruli were examined, including 1 with global sclerosis, 1 with small cellular crescent, 2 with large fibrocellular crescents, and 1 with fibrous crescent. The remaining glomeruli showed diffuse mesangial and endocapillary hypercellularity with lobulated accentuation. Segmental glomerular capillary loops were obliterated with neutrophil infiltration. Wire-loops and glomerular basement membrane double- contours were present. A few fibrin thrombi were seen in glomerular and focal afferent arterioles. Tubules showed some degree of acute injury (lumen dilatation and vacuolar degeneration) and severe atrophy (~ 60%). Patchy interstitial fibrosis and inflammation were also observed. The arteriolar wall was thickened with luminal stenosis(Fig1 B,C,D). Immunofluorescence staining showed “full-house” granular deposits along capillary loops and in mesangial areas (3 + IgG, 2 + IgM, 3 + IgA, 3 + C3, 3 + C1q, 1 + Kappa, and 2 + Lambda). Many focal tubular basement membrane deposits were present(Fig1 G,H). Electron microscopy revealed numerous electron dense deposits in the subepithelial, subendothelial, and mesangial areas. Mesangial interpositioning forming glomerular basement membrane double contours were confirmed. Podocyte foot processes were diffusely effaced. Tubuloreticular inclusions were not identified(Fig1 E,F). Pathologically, diffuse proliferative glomerulonephritis (membranoproliferative glomerulonephritis type III pattern) and TMA were suggested. Together with clinical presentations, a diagnosis of seronegative LN type IV + V with superimposed TMA was favored.
Treatment with plasma exchange was initiated, combined with prednisone acetate 50 mg daily, mycophenolate mofetil 0.5 g, and hydroxychloroquine sulfate 0.2 g twice daily, followed by rituximab 500 mg infusion for twice (total 1,000 mg). Hemodialysis was performed during the initial two months. Three months after hemodialysis discontinuation (5 months later), edema was significantly improved with persistent hypoproteinemia and proteinuria. Six months later, hemoglobin recovered and creatinine was normalized.