Long term anti-vascular endothelial growth factor receptor treatment impairs renal function in renal cell carcinoma

Background: The overall survival has been dramatically improving in metastatic renal cell carcinoma (mRCC) patients. Although anti-vascular endothelial growth factor receptor (VEGFR) treatment is one of essential therapeutic strategies for mRCC, the impact on renal function during their lifetime remains unclear. This study aimed to assess the comparison between the duration of anti-VEGFR treatment and chronic kidney disease (CKD) progression. Methods: : A total of 147 mRCC patients who started systemic therapy in Yamagata University Hospital from November 2005 to December 2018 were included in the study. We analyzed the probability of progression to CKD grades 4 and 5 using the Kaplan–Meier method and the log-rank test. To identify the factors independently associated with progression to CKD grade 4, multivariate analysis using logistic regression was performed with baseline eGFR, follow-up duration, duration with anti-VEGFR treatment, proteinuria, hypertension, and diabetes mellitus as the exposure variables. Results: : No patients with normal baseline renal function progressed to CKD grade 4 or 5. Two out of 85 patients with baseline CKD grade 3 progressed to grade 5 8 years after the start of the treatment. Three of five patients with baseline CKD grade 4 progressed to grade 5 within 2 years of starting the treatment. The estimated probability of the patients progressing to grade 4 was increased with worsening baseline CKD grade as determined by univariate analysis (P < 0.001). Multivariate analysis showed that baseline eGFR (P = 0.002), the duration of anti-VEGFR treatment (P = 0.014) and DM (P = 0.040) were independently correlated with progression to CKD grade 4. Conclusions: : Long-term anti-VEGFR treatment could impair renal function in mRCC patients with baseline CKD grade 3 or worse.