Factors decreasing nephrotoxicity of anti-VEGF antitumor drugs.

Anti-VEGF drugs that are widely used for treatment of malignancies can cause nephrotoxicity. Decreasing the risk of renal damage may allow prolonged use of antiangiogenic agents.

Aim

To assess the risk factors for nephrotoxicity of antiVEGF drugs.

Material and methods

In a prospective study, we enrolled 50 patients who were treated with anti-VEGF drugs in different regimens of chemotherapy. We assessed demographic factors, body mass index, blood pressure, antiangiogenic drug, and concomitant therapy. At baseline and at 8 week, we measured the levels of hemoglobin, D-dimer, serum lactate dehydrogenase (LDH), daily albuminuria, serum creatinine and glomerular filtration rate estimated using CKD-EPI formula (eGFRCKD-EPI). Logistic regression analysis was performed to assess risk factors for nephrotoxicity.

Results

At 8 week, decrease in eGFRCKD-EPI <60 ml/min/ 1.73 m2 was found in 21 (42%) of patients. CKD-EPI formula was more sensitive for assessment of nephrotoxicity compared to Cockcroft-Gault and MDRD formulas. Risk factors for early nephrotoxicity of antiangiogenic drugs were an initial decrease in GFR less than 80 ml/min/1,73 m2 and arterial hypertension. In the longer term, risk factors for treatment discontinuation due to nephrotoxicity were female gender and a progressive decrease in GFR. Achievement of target blood pressure and normal D-dimer levels during 8 weeks therapy were associated with a lower risk of nephrotoxicity.

Conclusion

Achievement of target blood pressure (<130/80 mm Hg) is required to reduce the risk of nephrotoxicity of anti-VEGF drugs. CKD-EPI or MDRD formulas should be used for monitoring of renal function during treatment, partcularly in patients with initial decrease of GFR less than 80 ml/min/1,73 m2.

Key words

Nephrotoxicity, anti-VEGF therapy, antitumor therapy, adverse events