Progressive bevacizumab-associated renal thrombotic microangiopathy

Abstract

Vascular endothelial growth factor (VEGF) is integral to the integrity of the glomerular filtration barrier. Bevacizumab is a humanized monoclonal antibody directed against VEGF with expanding clinical applications for metastatic solid tumours. We describe a case of a 61-year-old female with ovarian cancer and baseline chronic kidney disease who received three doses of bevacizumab and subsequently developed progressive renal clearance dysfunction and nephrotic range proteinuria. A renal biopsy was performed 4 months after drug discontinuation and was consistent with TMA. At baseline, prior to bevacizumab exposure, her estimated glomerular filtration rate (eGFR) was 44 mL/min/1.73 m(2) and she had no proteinuria. At the completion of therapy, eGFR was 27 mL/min/1.73 m(2) with 1+ proteinuria on urinalysis. Her renal failure and proteinuria continued to progress 5 months after discontinuation of bevacizumab therapy, at which time eGFR was 11 mL/min/1.73 m(2) and proteinuria was 5.5 g/24 h. Non-remitting TMA after bevacizumab therapy in patients with pre-existing chronic kidney disease has not been previously reported. Further studies are needed to assess the safety of this drug in patients with chronic kidney disease.

Keywords: VEGF inhibitor; bevacizumab; renal failure; thrombotic microangiopathy.

Fig. 1

(a) Glomerulus showing mesangiolysis with extravasated RBCs and probable thrombus in peripheral capillary loop (haematoxylin and eosin, 400×). (b) Renal parenchyma displaying interstitial fibrosis and tubular atrophy with associated chronic inflammation (haematoxylin and eosin, 200×).

Fig. 2

Serum creatinine and proteinuria in patients before, during and after bevacizumab therapy. Baseline: median and range of baseline serum creatinine (n = 8) and proteinuria (n = 8) for patients prior to with bevacizumab therapy. Cessation of bevacizumab: median and range of peak serum creatinine (n = 7) and proteinuria (n = 9) for patients during bevacizumab therapy. Recovery: median and range of recovery serum creatinine (n = 5) and proteinuria (n = 7) for patients after recovery with bevacizumab therapy. For previous cases, if a serum creatinine value was not reported but kidney function was described as ‘normal’, a serum creatinine value of 1.2 was assigned. Vertical lines are median and range values for serum creatinine (dashed) and proteinuria (solid) in previously reported cases; the horizontal lines are values for creatinine and proteinuria for the patient reported in this case.