The Impact of Renal Impairment on Survival Outcomes in Patients With Metastatic Renal Cell Carcinoma Treated With Tyrosine Kinase Inhibitors

Abstract

Purpose: It remained unclear whether tyrosine kinase inhibitors (TKIs) related renal impairment had impact on the survival of patients with metastatic renal cell carcinoma (mRCC). Methods: Clinicopathological parameters of patients with mRCC treated with TKIs were retrospectively reviewed. Blood urea nitrogen (BUN), proteinuria and estimated glomerular filtration rate (eGFR) at baseline and during TKIs treatment were recorded. BUN > 7.1mol/L, eGFR <60 ml/min/1.73m2 and/or proteinuria level > 0.3 g/L were defined as renal impairment. eGFR and proteinuria were furtherly classified into different levels. Treatment outcomes were defined as progression-free survival (PFS) and overall survival (OS). Results: At baseline, the presence of abnormal BUN, eGFR and proteinuria level were observed in 25 (22.7%), 27 (25.5%) and 30 (27.3%) patients, which increased to 46 (41.8%), 55 (50.0%) and 64 (58.2%) respectively after TKIs treatment. In the whole cohort (N = 110), survival analysis suggested that only post-treatment renal impairment was related to survival outcomes. Interestingly, sub-analysis showed that post-treatment eGFR level (p = 0.004), proteinuria (p = 0.014) and eGFR decrease >10% (p = 0.012) and elevated proteinuria compared with baseline (p = 0.006) were statistically correlated with OS among patients without RI at baseline (N = 51). On the contrary, deterioration of renal impairment after TKIs treatment in patients with renal impairment at baseline (N = 59) had no relationship with either PFS or OS. Furthermore, eGFR (p = 0.020) and eGFR decrease >10% (p = 0.016) within 1 year after TKIs therapy were potential biomarkers for OS. Conclusion: Dynamic changes of TKI-induced RI during TKIs treatment, especially eGFR and proteinuria level, could be considered as potential biomarkers predicting survival outcomes of mRCC patients.

Adverse events as potential predictive factors of activity in patients with advanced hepatocellular carcinoma treated with lenvatinib

“…Proteinuria is a common AE with lenvatinib and other TKIs, and its management usually relies on drug suspension and subsequent resumption upon improvement 41,42 . Our finding is consistent with other reports: although a correlation between TKI‐induced proteinuria and survival has been reported in renal cell carcinoma, 43 a prognostic value for lenvatinib‐induced proteinuria has not been showed in HCC 44 …”

Comprehensive Systematic Review of Biomarkers in Metastatic Renal Cell Carcinoma: Predictors, Prognostics, and Therapeutic Monitoring

“…The results demonstrated that patients with impaired renal function had significantly worse overall survival compared to those with normal renal function. This highlights the importance of considering renal impairment in the management and treatment of mRCC patients receiving TKIs [118].…”