GLOMERULAR MICROANGIOPATHY AND PROTEINURIA ASSOCIATED WITH LENVATINIB THERAPY IN THYROID CANCER: TWO CASE REPORTS

GLOMERULAR MICROANGIOPATHY AND PROTEINURIA ASSOCIATED WITH LENVATINIB THERAPY IN THYROID CANCER: TWO CASE REPORTS

Elaine Phua^1,2, Mrudula Krishnaswamy^3,4, Jenny Chen^2,5, Roxana Tsui³, Beba Attia³, Max Yan⁶, Stephen May<sup>1

1</sup>Tamworth Rural Referral Hospital, Tamworth, NSW, Australia
²Renal Department, Illawarra Shoalhaven Local Health District, Wollongong, NSW, Australia
³NSW Health Pathology, Concord Repatriation Hospital, Concord, NSW, Australia
⁴Faculty of Medicine and Health (Concord Clinical School), The University of Sydney, Concord, NSW, Australia
⁵Faculty of Medicine, University of Wollongong, Wollongong, NSW, Australia
⁶NSW Health Pathology, Prince of Wales Hospital, Randwick, NSW, Australia

Abstract

Background:
Lenvatinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) approved for use against multiple cancer types including radioiodine-refractory differentiated thyroid carcinoma. Hypertension and proteinuria are common adverse effects seen with Lenvatinib therapy. We describe the clinical and histopathologic features of two cases of Lenvatinib-induced glomerulopathy (Patient A and B) with a distinctive histologic pseudothrombotic and membranoproliferative pattern mimicking thrombotic microangiopathy (TMA).

Case Reports
Patient A, a 93-year-old male, developed kidney impairment over a 6 month period (Creatinine (Cr) 165umol/L, baseline Cr 125 umol/L), nephrotic-range proteinuria (urine albumin:creatinine (uA:Cr) 603mg/mmol), reduced serum albumin (23g/L) and anasarca two-years after commencing Lenvatinib therapy for metastatic papillary thyroid carcinoma (mPTC). Patient B, a 73-year-old male, developed peripheral oedema, proteinuria (uA:Cr 171mg/mmol), low serum albumin (21g/L) and preserved kidney function (Cr 76umol/L) five-years after commencing Lenvatinib therapy for mPTC diagnosed seventeen-years prior. Light microscopy of both kidney biopsies showed common features of sclerosing lesions, variable double contour formation and PAS-positive hyaline pseudothrombi occluding dilated glomerular capillaries. Electron microscopy confirmed double contours with moderate foot-process effacement and subendothelial deposition of material with a coarse and vaguely organised fine structure. Nephrotic syndrome resolved in patient A after medication cessation. Lenvatinib was continued in patient B alongside supportive antiproteinuric therapy, with observed improvement in proteinuria.

Conclusion
This report aims to raise awareness given the increasing use of TKIs and consequently, TKI-related kidney complications. Treatment of Lenvatinib-induced glomerulopathy remains challenging, particularly with competing therapeutic priorities. Screening and early detection may minimise interruption to therapy.

Biography

Bio to come