Immune checkpoint inhibitors further aggravate proteinuria in patients with metastatic renal cell carcinoma after long-term targeted therapy

Background: Increasing number of patients with metastatic renal cell carcinoma (mRCC) are receiving subsequent programmed cell death protein-1 (PD-1) inhibitor combination therapy following tyrosinekinase inhibitor (TKI) resistance. To explore whether PD-1 inhibitor would further deteriorate proteinuria and renal function, we observed their proteinuria's and renal function's condition since the administration of PD-1 inhibitor. Methods: To assess the change in proteinuria and renal function, the data of 141 patients with mRCC treated with TKI were collected, 66 of whom were further prescribed PD-1 inhibitor. Proteinuria and estimated glomerular filtration rate (eGFR) were measured and analyzed. Logistic regression models were established to identify the predictors of proteinuria deterioration and significant eGFR decline (>= 15%). Results: Of the 141 patients, 74 (52%) had an increase in proteinuria level after an average of 22.98 months of TKI treatment. In multivariate analysis, longer duration of TKI (>12 months) and administration of PD-1 inhibitor were independent predictors for proteinuria deterioration. The median eGFR decreased from 81.56 mL/min/1.73 m2 to 66.75 mL/min/1.73 m2 after TKI treatment. Logistic regression identified older age (>60 years old) and longer duration of TKI (>12 months) as independent predictors for significant eGFR decline. Finally, of the 66 patients who received subsequent PD-1 inhibitor, 34 had sufficient proteinuria and eGFR data at follow-up. The level of proteinuria increased further after the administration of PD-1 inhibitor, although the decrease in eGFR was not statistically significant (P=0.182). Log-rank analysis identified proteinuria deterioration and eGFR decline were both significantly associated with patent's survival (P<0.001). Conclusions: Targeted therapy was associated with an increase in proteinuria level and a decrease in eGFR in patients with mRCC. The administration of PD-1 inhibitor contributed to exacerbation in proteinuria, but no significant difference in a decrease of eGFR was observed.