Occurrence of tyrosine kinase inhibitors-induced renal impairment and its predictive value for the prognosis of patients with metastatic renal cell carcinoma.

Abstract

693 Background: To investigate the tyrosine kinase inhibitors (TKIs) related renal impairment (RI) on the therapy efficacy and survival of patients with metastatic renal cell carcinoma (mRCC). Methods: Clinical and pathological parameters of patients with mRCC treated with TKIs were retrospectively reviewed. Blood urea nitrogen (BUN), proteinuria(PU) and estimated glomerular filtration rate (eGFR) were defined as main renal function related parameters, and their levels at the time of pre- and post- TKIs treatment were recorded and analyzed. Abnormal BUN, PU and/or eGFR were defined as RI. Primary and secondary treatment outcomes were progression-free survival (PFS) and overall survival (OS), and tumor response was defined as secondary treatment outcome. SPSS 24.0 and GraphPad Prism 7.0a were used for statistical analyses. Results: A total of 110 patients were included in this study. At baseline, patients with abnormal BUN, abnormal eGFR and PU were 25 (22.7%), 27 (25.5%) and 30 (27.3%), respectively, which increased to 46 (41.8%), 55 (50.0%) and 64(58.2%) after TKI treatment. Survival analysis showed that baseline RI had no impact either on prognosis, or the effectiveness of TKIs. On the contrary, for post-treatment RI, PU level, elevated PU, and eGFR level were independently related to PFS and OS. Besides, eGFR decrease >10% was indicated for longer OS time (19.0 vs 41.0 months, p=0.034). Sub-analysis suggested that, among 51 patients without RI pre-TKI therapy, eGFR level (P=0.004), eGFR decrease > 10% (P=0.012), PU level (P=0.014) as well as elevated PU level (P=0.006) were statistically correlated with OS time. However, the similar trend was not identified in those with baseline RI. Furthermore, baseline eGFR level (P=0.020) and eGFR decrease > 10% (P=0.016) within 1y after TKI therapy were identified to be effective biomarkers predicting OS. Conclusions: The occurrence of TKI-induced RI was indicated for better tumor response and survival outcomes, and provide valuable information for the individual treatment of mRCC patients. Thus, routinely monitoring of renal function, especially eGFR and PU, was highly recommended in TKIs-treated mRCC patients.