To systematically evaluate the risk of proteinuria and serious proteinuria due to vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) in cancer patients.

Randomized controlled trials (RCTs) of VEGFR-TKI in the treatment of tumors were collected by searching relevant databases at home and abroad (up to March 2023). The patients who were treated with VEGFR-TKI were enrolled into the trial group, and those who received placebo or other drugs (except for VEGFR-TKI) were enrolled into the control group. The outcomes included the incidence of proteinuria and serious proteinuria. The quality of the enrolled literature was evaluated using the Jadad scoring system. Meta-analysis was conducted with STATA 12.0 software. The results are expressed as relative risk (RR) and 95% confidence interval (CI).

A total of 19 RCTs involving 5 246 patients were enrolled, including 3 173 in the test group and 2 073 in the control group. Literature quality evaluation showed that 18 articles were of high quality and 1 was of low grade. Meta-analysis showed that the incidence of proteinuria and serious proteinuria in the trial group was significantly higher than that of the control group, respectively [20.74% (658/3173) vs 7.48% (155/2073), RR=2.54, 95%CI (1.86~3.46), P<0.001; 2.87% (91/3173) vs 0.43% (9/2073), RR=4.41, 95%CI (2.47~7.89), P<0.001]. Subgroup analysis showed that the incidence of proteinuria and serious proteinuria in the pazopanib group was significantly higher than that of the control group [11.69% (124/1061) vs 4.35% (39/897), RR=2.80, 95%CI (1.11~7.08), P<0.05; 1.79% (19/1061) vs 0.45% (4/897), RR=3.57, 95%CI (1.25~10.25), P<0.05]; the incidence of proteinuria in the apatinib group, fruquintinib group, regorafenib group, and anlotinib group was significantly higher than that of the control group [44.27% (112/253) vs 14.88% (25/168), RR=2.85, 95%CI (1.93~4.21), P<0.001; 40.41% (137/339) vs 23.21% (39/168), RR=1.74, 95%CI (1.28~2.35), P<0.001; 8.27% (55/665) vs 1.79% (6/335), RR=4.51, 95%CI (1.97~10.34), P<0.001; 27.12% (96/354) vs 12.00% (24/200), RR=2.16, 95%CI (1.43~3.27), P<0.001]; and the incidence of serious proteinuria in the lenvatinib group was significantly higher than that of the control group [8.97% (28/312) vs 0.55% (1/181), RR=11.78, 95%CI (2.01~68.93), P<0.01].

The application of VEGFR-TKI in cancer patients can increase the risk of proteinuria and serious proteinuria. When pazopanib and lenvatinib are used clinically, renal function monitoring should be strengthened.