Immune checkpoint inhibitor therapy worsens proteinuria in patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy, according to findings from a new Chinese study.

Among 141 Chinese patients with mRCC treated with tyrosine kinase inhibitors (TKIs), 74 (52%) had an increase in proteinuria after a mean 23 months of treatment, Zhiling Zhang, MD, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China, and colleagues reported in Translational Andrology and Urology. The proportion of patients with grade 1, 2, and 3 proteinuria all significantly increased. During TKI treatment, the median estimated glomerular filtration rate (eGFR) also significantly decreased from 81.6 to 66.8 mL/min/1.73 m2. Half of patients had a significant eGFR decline of 15% or more. Age older than 60 years (vs 60 years or younger) and TKI therapy for longer than 12 months (vs 12 months or less) independently predicted significant 2.9- and 2.8-fold increased odds of eGFR decline, respectively.

Among the 141 patients, 66 received subsequent treatment with a programmed cell death protein 1 (PD-1) inhibitor. An analysis of follow-up data from 34 of the 66 patients showed that proteinuria significantly worsened in 50% after the administration of a PD-1 inhibitor. During immunotherapy, proteinuria increased by 1, 2, and 3 grades in 29%, 15%, and 6% of patients, respectively. During the immunotherapy phase, 80% of patients displayed proteinuria.

Continue Reading

In multivariate analysis, TKI treatment for longer than 12 months (vs 12 months or less) and use of a PD-1 inhibitor (vs no use) were independently associated with a 2.5- and 2.6-fold increased risk of an increase in proteinuria, respectively, according to Dr Zhang’s team. A log-rank analysis showed that worsening proteinuria and eGFR decline were significantly associated with a 3.0- and 2.5-fold increased risk of poor patient survival, respectively.

Severe renal impairment prompted 11% and 11% of patients to discontinue TKI therapy and PD-1 inhibitor therapy, respectively.

“Our results suggest that active renal function monitoring should be performed especially in patients who have been scheduled for PD-1 inhibitor or underwent TKI therapy for more than one year,” Dr Zhang’s team concluded.


Ning K, Wu Z, Zou X, et al. Immune checkpoint inhibitors further aggravate proteinuria in patients with metastatic renal cell carcinoma after long-term targeted therapy. Transl Androl Urol. 11(3):386-396. doi:10.21037/tau-21-1015