Risk factors and early biomarkers of nephrotoxicity associated with the use of anti-VEGF drugs.

Abstract

e24079 Background: Anti-angiogenic anticancer drugs that block VEGF can cause kidney damage (Fujii et al., 2019). Among the mechanisms of nephrotoxicity thrombotic microangiopathy (TMA) of renal vessels can be distinguished (Estrada et al., 2019). TMA can be accompanied the development of anemia, excessive schistocytes, as well as increased LDH levels and a low platelet count, which indicated the occurrence of endothelial dysfunction and microangiopathic processes (Hauser et al, 2009). The goal of this study was to assess the risk factors of early nephrotoxicity and the utility of NGAL, KIM-1, HIF-1α and nephrin levels in urine as early biomarkers of nephrotoxicity. Methods: The study included 50 patients who received anti-VEGF drugs (aflibercept, bevacizumab or ramucirumab). Nephrotoxicity was determined as a decrease in glomerular filtration rate (GFR) to < 60 ml/min/1.73m2 at 8 weeks from the initiation of therapy. The laboratory parameters and the levels of KIM-1, NGAL, HIF-1α and nephrin in urine samples were determined by ELISA before treatment and after 1, 2, 4 and 8 weeks of treatment. To assess risk factors for nephrotoxicity we analyzed primary clinical and laboratory parameters. Results: Nephrotoxicity at 8 weeks was achieved in 21 (42%) of patients. A statistically significant decrease in hemoglobin and platelet count by 20 and 26%, respectively, from the initial level was observed. An increase in the number of schistocytes and a slight increase in LDH levels were also observed. The increase in NGAL, KIM-1 and nephrin levels was statistically significant in 1 weeks and the increase of HIF-1α in 2 weeks after the start of therapy (p = 0.001). The unfavorable predictors of nephrotoxicity as well as the favorable predictors in terms of decreasing renal function are presented in Table. ROC analysis demonstrated high sensitivity and specificity: NGAL – AUC 0.7; KIM-1 – AUC 0.69; HIF-1α – 0.7; nephrin – AUC 0.7. Conclusions: We report a significant increase in the parameters of microangiopathic hemolysis and in urine biomarkers of tubular and podocytic damage as well as hypoxia by the 8th week of treatment. We suggest that the TMA process can take part in renal damage. Increased levels of NGAL, KIM-1, HIF-1α and nephrin in the urine reflect the renal damage processes and have higher sensitivity and specificity then serum creatitine. The independent risk factors for nephrotoxicity are determined. [Table: see text]