Clinical and laboratory signs and risk factors for nephrotoxicity, associated with antiangiogenic drugs

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Abstract

Background. Anti-angiogenic anticancer drugs that block the vascular endothelial growth factor signaling pathway can cause renal damage. Assessment of the risk of nephrotoxicity allows developing optimal treatment approaches and ensuring the relative safety of therapy.

Aim. To assess early clinical and laboratory manifestations and risk factors for nephrotoxicity of antiangiogenic drugs.

Materials and methods. The study included 50 patients who received antiangiogenic drugs in different regimens of chemotherapy. Demographic factors, body mass index, blood pressure levels, type of antiangiogenic drug, and concomitant therapy were assessed. Before treatment and over a period of 8 weeks, the levels of hemoglobin, number of platelets and schistocytes, D-dimer levels, serum lactate dehydrogenase (LDH) levels, as well as daily proteinuria and serum creatinine and eGFRCKD-EPI were assessed. Linear regression analysis was performed to assess risk factors for nephrotoxicity and arterial hypertension (AH).

Results. The median age of patients was 46 [34–57] years, 22 (44%) men and 28 (56%) women. AH developed in 52%, a decrease in eGFR – in 42%, along with a decrease in hemoglobin levels and an increase in LDH levels – at 2 weeks of therapy. The numbers of schistocytes and platelets significantly decreased by 8 weeks of therapy. Risk factors for impaired renal function during treatment with antiangiogenic drugs were an initial decrease in GFR less than 80 ml/min/1.73 m2, an increase in D-dimer levels, and a decrease in hemoglobin levels by 8 weeks of treatment. The risk factors for AH during therapy were the initial decrease in eGFR less than 80 ml/min/1.73 m2 and no prophylactic anticoagulant therapy.

Conclusion. Early signs of nephrotoxicity of antiangiogenic anticancer drugs were a decrease in eGFR and AH. The independent risk factors for nephrotoxicity were the initial decrease in eGFR, an increase in D-dimer levels, and a decrease in hemoglobin levels at 8 weeks of treatment, while the prophylactic use of anticoagulant therapy reduced this risk in our study.

About the authors

Katerina S. Grechukhina

Lomonosov Moscow State University; Loginov Moscow Clinical Scientific and Practical Center

Author for correspondence.
Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-0616-5477

аспирант каф. внутренних болезней ФГБОУ ВО «МГУ им. М.В. Ломоносова», врач- онколог ГБУЗ «МКНЦ им. А.С. Логинова»

Russian Federation, Moscow; Moscow

Natalia V. Chebotareva

Sechenov First Moscow State Medical University (Sechenov University)

Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0003-2128-8560

д-р мед. наук, проф. каф. внутренних, профессиональных болезней и ревматологии Института клинической медицины им. Н.В. Склифосовского ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow

Liudmila G. Zhukova

Loginov Moscow Clinical Scientific and Practical Center

Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0003-4848-6938

д-р мед. наук, проф., зам. дир. по онкологии ГБУЗ «МКНЦ им. А.С. Логинова»

Russian Federation, Moscow

Tatiana N. Krasnova

Lomonosov Moscow State University

Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-7647-3942

зав. каф. внутренних болезней ФГБОУ ВО «МГУ им. М.В. Ломоносова»

Russian Federation, Moscow

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Supplementary files

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2. Fig. 1. Blood pressure, glomerular filtration rates, proteinuria patterns during antiangiogenic treatment.

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3. Fig. 2. Hemoglobin, lactate dehydrogenase, platelets and schystocytes patterns during antiangiogenic treatment.

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