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.