POS-490 GLOMERULAR MICROANGIOPATHY ASSOCOATED WITH PROLONGED USE OF BEVACIZUMAB IN A PATIENT WITH RENAL-CELL CARCINOMA - CASE REPORT

Abstract

Drug-induced thrombotic microangiopaty (TMA) known to be associated with the usage of the vascular endothelial growth factor inhibitors; since 2007, several cases of TMA, associated with bevacizumab, had been reported. In 2019, Person et al. described specific pattern of injury in 17 patients receiving bevacizumab, and introduced the term bevacizumab-associated glomerular microangiopathy instead of TMA; none on these patients had renal-cell carcinoma We present a case of glomerular microangiopathy, associated with prolonged bevacizumab treatment in a patient with renal-cell carcinoma 61 years old Caucasian female was referred for kidney biopsy. She underwent resection of her right kidney for the renal-cell carcinoma twice, and received bevacizumab for 8 years; 18 months before admission she developed new-onset arterial hypertension and nephrotic syndrome. At admission, she had general edema, her blood pressure was 200/100 mm Hg; the rest of her physical examination was unremarkable. Her urine protein excretion was 6400mg/24 hours with blunt urine sediment; hemoglobin was 10.4g/dL, platelet count was 322x109/L, ESR 59mL/min, serum creatinine 120µmol/L, total protein 5.4g/dL, serum albumin 2.4g/dL, LDH 224U/L. Other blood chemistry parameters, immunoglobulins, C3, C4 and CRP levels were normal. ECG, chest CT, kidneys and abdomen ultrasound showed nothing but right kidney postoperative changes and mild bilateral hydrothorax. Kidney biopsy light microscopy on paraffin-imbedded sections stained with haematoxylin-eosin, periodic acid-Schiff (PAS), Masson’s trichrome, and Jones silver found 10 sclerosed glomeruli, the rest 26 were enlarged, with lobular appearance, without hypercellularity or crescents. Most capillary lumens were widened, with single-contour capillary walls, lacking endothelial layer, and occupied with homogenous acellular mild eosinophilic, PAS negative, non-fuchsinophilic, Jones-negative coarse pseudothrombi (Figures 1, 2). Diffuse acute tubular epithelial injury with brush-border loss, without casts or interstitial fibrosis/tubular atrophy, and mild thickening of arterioles and small arteries due to muscular layer hypertrophy was found. Immunofluorescence on formalin fixed paraffin-embedded tissue with FITC-conjugated antibodies to human IgA, IgG, IgM, C1q, C3, fibrinogen, kappa and lambda light chains showed diffuse homogenous IgA, IgG, IgM, C1q, C3, fibrinogen, kappa and lambda +/++ expression in pseudothrombi. Based on the presence of pseudothrombi and absence of the TMA clinical features we diagnosed bevacizumab-associated glomerular microangiopathy, discontinued bevacizumab, and started ACE-inhibitors and aspirin with the outpatient follow-up. A month later, her edema resolved, blood pressure was 150/90 mm Hg, urine protein excretion was 780mg/24 hours, serum albumin 3.1g/dL, and serum creatinine 112µmol/L. A year later, she was doing well, without edema; her blood pressure was 130/80 mm Hg, hemoglobin 13.0g/dL, total protein 7.3g/dL, serum albumin 4.2g/dL, and serum creatinine 88µmol/LView Large Image Figure ViewerDownload Hi-res image Download (PPT) The patient treated with bevacizumab for 8 years developed bevacizumab-associated glomerular microangiopathy, which is an extremely rare complication in a renal-cell carcinoma setting. Withdrawn of bevacizumab lead to the resolution of clinical symptoms and restoration of kidney function