Urinary biomarkers of kidney injury in patients treated with anti-VEGF drugs
- Authors: Grechukhina K.S.1,2, Chebotareva N.V.1,3, Zhukova L.G.2, Androsova T.V.3, Karpov V.V.3, Krasnova T.N.1,3
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Affiliations:
- Lomonosov Moscow State University
- Loginov Moscow Clinical Scientific Center
- Sechenov First Moscow State Medical University (Sechenov University)
- Issue: Vol 94, No 6 (2022)
- Pages: 725-730
- Section: Original articles
- URL: https://journals.rcsi.science/0040-3660/article/view/109608
- DOI: https://doi.org/10.26442/00403660.2022.06.201561
- ID: 109608
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Abstract
Background. Antiangiogenic drugs are widely used in oncological practice and are aimed at inhibiting angiogenesis. Despite the high antitumor efficacy, their use may be limited by nephrotoxicity, and therefore the search for early biomarkers of kidney damage remains relevant, which will preserve a favorable safety profile of therapy.
Aim. To determine urinary biomarkers of tubular and podocyte damage in patients receiving treatment with antiangiogenic drugs.
Materials and methods. The study included patients (n=50) who received intravenous anti-VEGF drugs (aflibercept, bevacizumab, ramucirumab) in various chemotherapy regimens. Concentrations of tubular damage markers KIM-1 (Kidney Injury Molecule-1) and NGAL (Neutrophil Gelatinase-Associated Lipocalin), hypoxia marker HIF-1α (Hypoxia-Inducible Factor 1-alpha) in urine samples were determined by enzyme-linked immunosorbent assay (ELISA) before treatment, and during 8 weeks of treatment. To assess the risk factors for kidney damage, a logistic regression analysis was performed with the inclusion of the main clinical and laboratory parameters.
Results. A decrease in the calculated GFR of CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Formula) of less than 60 ml/min per 1.73 m2 at week 8 of treatment was noted in 42% of patients. An increase in NGAL, KIM-1, HIF-1α and nephrin in urine during the first two weeks of therapy predicted the development of renal damage by the 8th week of follow-up. When constructing ROC-curves, the high sensitivity and specificity of these urinary indicators as prognostic markers were established. Among the clinical and laboratory indicators, independent unfavorable prognostic factors of nephrotoxicity were an initial decrease in eGFR, a history of hypertension, an increase in the concentration of KIM-1 and HIF-1α in urine during the first two weeks of therapy.
Conclusion. The predictors of renal damage in the treatment with antiangiogenic drugs were previously an increase in NGAL, KIM-1 and HIF-1α in urine during the first two weeks after the start of therapy.
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##article.viewOnOriginalSite##About the authors
Katerina S. Grechukhina
Lomonosov Moscow State University; Loginov Moscow Clinical Scientific Center
Author for correspondence.
Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-0616-5477
пирант каф. внутренних болезней, врач-онколог
Russian Federation, Moscow; MoscowNatalia V. Chebotareva
Lomonosov Moscow State University; Sechenov First Moscow State Medical University (Sechenov University)
Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0003-2128-8560
д-р мед. наук, проф., проф. каф. внутренних болезней, проф. каф. внутренних, профессиональных болезней и ревматологии Института клинической медицины им. Н.В. Склифосовского
Russian Federation, Moscow; MoscowLiudmila G. Zhukova
Loginov Moscow Clinical Scientific Center
Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0003-4848-6938
д-р мед. наук, проф., зам. дир. по онкологии
Russian Federation, MoscowTatiana V. Androsova
Sechenov First Moscow State Medical University (Sechenov University)
Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-9951-126X
канд. мед. наук, доц. каф. внутренних, профессиональных болезней и ревматологии Института клинической медицины им. Н.В. Склифосовского
Russian Federation, MoscowVladimir V. Karpov
Sechenov First Moscow State Medical University (Sechenov University)
Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0003-2048-3401
канд. мед. наук, доц. каф. внутренних, профессиональных болезней и ревматологии Института клинической медицины им. Н.В. Склифосовского
Russian Federation, MoscowTatiana N. Krasnova
Lomonosov Moscow State University; Sechenov First Moscow State Medical University (Sechenov University)
Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-7647-3942
канд. мед. наук, зав. каф. внутренних болезней, доц. каф. внутренних болезней
Russian Federation, Moscow; MoscowReferences
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