Lenvatinib-induced renal failure: two first-time case reports and review of literature

ABSTRACT

Introduction: Lenvatinib (LEN) is a multi-kinase anti-angiogenic drug recently approved in several cancers. LEN is not easily manageable due to its complex safety profile. Proteinuria and renal failure (RF) were reported among the most frequent LEN-induced adverse events (AEs), often leading to discontinuations or dose modifications. Understanding the pathogenesis of these AEs could ameliorate the management of LEN-induced renal toxicity.

Areas covered: We present two cases of LEN-induced renal failure (LIRF) with different pathogenesis. 1) LIRF with severe proteinuria in a man treated for a metastatic papillary thyroid carcinoma. Kidney biopsy showed a glomerular damage secondary to LEN, having excluded other causes of RF. 2) LIRF without proteinuria in a woman with metastatic adenoid cystic carcinoma of minor salivary gland. A tubulointerstitial nephropathy was supposed by clinical evaluation and laboratory tests. Effective management was obtained by oral steroids without interrupting LEN.

Expert opinion: The case 1 presented for the first time the histological picture of LIRF with a classical glomerular damage leading to secondary proteinuria and tubular failure. Case 2 showed an alternative LIRF pattern of likely tubulointerstitial injury without proteinuria. These reports reflect two sides of the same coin, both to be considered in case of LIRF.

KEYWORDS:

• Antiangiogenic
• lenvatinib
• nephropathy
• proteinuria
• renal failure
• salivary gland cancer
• thyroid cancer
• toxicity
• VEGF
• VEGFR

Article highlights

• Proteinuria is recognized as a class side effect among antiangiogenic drugs, such as lenvatinib

• Proteinuria often leads to lenvatinib interruptions and/or dose modifications

• Lenvatinib-induced renal failure (LIRF) might be associated with glomerular damage, with secondary proteinuria and tubular injury

• A primary tubulointerstitial injury may be identified as alternative pattern of LIRF without proteinuria development

• Low-dose steroids can be used to manage the primary non-glomerular lenvatinib-induced damage without requiring lenvatinib interruption or discontinuation

This box summarizes key points contained in the article.

Acknowledgment

The Authors dedicate this work to dr. Augusto Genderini, who passed away before the completion of this manuscript. Without his essential contribution this work could not be realized.

Declaration of interest

L Licitra reports grants and personal fees from Eisai, Merck Sharp & Dohme, Boehringer Ingelheim, Novartis, Astrazeneca, Roche; personal fees from Bristol-Myers Squibb; grants, personal fees and other (travel expenses) from Merck-Serono, Bayer, Debiopharm, Sobi. L Locati reports honoraria from Eisai. P Bossi reports honoraria or consultation fees from Roche, Merck Serono, Mundipharma, Kyowa Kyrin and Astra Zeneca.

Additional information

Funding

This paper was not funded.