A case of pre-eclampsia-like glomerular endothelial injury in a patient with hepatocellular carcinoma treated with tyrosine kinase inhibitors

Abstract

Background: Glomerular endotheliosis is the pathognomonic glomerular lesion in pre-eclampsia and has also been described in cancer patients treated with tyrosine kinase inhibitors. We report a case of glomerular endotheliosis revealed by kidney biopsy in a cancer patient receiving lenvatinib monotherapy followed by intermittent combination therapy with bevacizumab and atezolizumab. Case: The patient, a male in his sixties with advanced hepatocellular carcinoma, developed proteinuria and hypoalbuminemia, and therefore lenvatinib was discontinued 15 weeks after initiation. As improvement was evident 5 weeks after drug withdrawal, intermittent combination therapy with bevacizumab and atezolizumab was started, but as the urine protein and serum albumin levels again decreased, the medication was discontinued after 41 weeks. A renal biopsy demonstrated pre-eclampsia-like lesions on light and electron microscopy, including occlusion of glomerular peripheral capillary lumina by swollen reactive endothelial cells and diffuse thickening of the glomerular capillary basement membrane, resembling glomerular endotheliosis. Capillary endothelial damage caused by tyrosine kinase inhibitors on a background of diabetic nephropathy was diagnosed, and the patient was started on an angiotensin II receptor antagonist, resulting in a decrease of urinary protein to the pre-treatment level 3 months later. Conclusion: Administration of tyrosine kinase inhibitors to patients with renal impairment is associated with a high risk of severe proteinuria, and the initiation and continuation of medication requires careful consideration.