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Case Reports
. 2020 Nov;9(4):295-300.
doi: 10.1007/s13730-020-00474-w. Epub 2020 Apr 11.

Nintedanib-induced glomerular microangiopathy: a case report

Masataka Hasegawa  1 , Atsuko Uehara  2 , Tomo Suzuki  1   3 , Reio Sekine  4 , Masahiko Yazawa  1 , Daisuke Ichikawa  1 , Junki Koike  5 , Yugo Shibagaki  1
Affiliations
Case Reports

Nintedanib-induced glomerular microangiopathy: a case report

Masataka Hasegawa et al. CEN Case Rep. 2020 Nov.

Abstract

Nintedanib, a triple tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has been used in idiopathic pulmonary fibrosis and adenocarcinoma in advanced non-small cell lung cancer. Although vascular endothelial growth factor inhibitors have been reported to cause endothelial injury and glomerular microangiopathy, nintedanib-induced glomerular microangiopathy has not been reported. A 68-year-old man with a history of primary aldosteronism, idiopathic pulmonary fibrosis, and pleomorphic carcinoma of the lung developed proteinuria and leg edema after nintedanib initiation. Kidney biopsy revealed prominent endothelial and mesangial injury. Proteinuria improved after nintedanib withdrawal. To the best of our knowledge, this is the second case report of nintedanib-induced glomerular microangiopathy. Although the incidence of nephropathy among patients receiving nintedanib is unknown at this moment, we recommend monitoring urinary protein excretion and blood pressure in patients receiving nintedanib and performing kidney biopsy to determine any histopathological change.

Keywords: Glomerular microangiopathy; Nintedanib; Onconephrology; Proteinuria; Pulmonary fibrosis.

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Conflict of interest statement

The authors have declared that no conflict of interest exists.

Figures

Fig. 1
Fig. 1
Clinical images of the present case. (A) Lung tumor on the right upper lobe was evident on chest computed tomography 2 years prior to the referral. (B) Pulmonary fibrosis is observed on bilateral lower part prior to nintedanib initiation
Fig. 2
Fig. 2
Histological findings of the kidney biopsy performed after the onset of proteinuria. (A) Mild mesangial proliferation and widely expanded subendothelial area occupied by hyaline-like materials with some huge subendothelial deposition (arrows). (B) Mesangiolysis (arrows) and double contour. (C) Blue-tinged subendothelial deposition (arrows) suggesting that the depositions are infiltrates of plasma. (D) Red-tinged subendothelial deposition (arrows) suggesting that the deposition is plasma itself. Electron microscopy finding showing unremarkable foot process effacement (E) and electron-dense deposits (arrows) in subendothelial and mesangial areas (F)
Fig. 3
Fig. 3
Clinical course of the present case regarding serum albumin and urine protein levels before and after nintedanib treatment. The period of nintedanib and timing of kidney biopsy are shown
See this image and copyright information in PMC

References

    1. Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, Brown KK, Flaherty KR, Noble PW, Raghu G, Brun M, Gupta A, Juhel N, Klüglich M, du Bois RM. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365:1079–1087. doi: 10.1056/NEJMoa1103690. - DOI - PubMed
    1. Richeldi L, du Bois RM, Raghu G, Azuma A, Brown K, Ulrich C, Cottn V, Klaherty K, Hansell D, Inouei Y, Kim DS, for the INPULSIS Trial Investigators et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071–2082. doi: 10.1056/NEJMoa1402584. - DOI - PubMed
    1. Reck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowski M, von Pawel J, Gottfried M, Bondarenko I, Liao M, Gann CN, Barrueco J, Gaschler-Markefski B, LUME-Lung Study Group Novello S Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014;15:143–155. doi: 10.1016/S1470-2045(13)70586-2. - DOI - PubMed
    1. Estrada CC, Maldonado A, Mallipattu SK. Therapeutic inhibition of VEGF signaling and associated nephrotoxicities. J Am Soc Nephrol. 2019;30:187–200. doi: 10.1681/ASN.2018080853. - DOI - PMC - PubMed
    1. Ismail I, Nigam S, Parnham A, Srinivasa V. Anti-glomerular basement membrane glomerulonephritis following nintedanib for idiopathic pulmonary fibrosis: a case report. J Med Case Rep. 2017;11:214. doi: 10.1186/s13256-017-1384-2. - DOI - PMC - PubMed

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