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No Correlation Between Proteinuria and Renal Function in Patients with Unresectable Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab: ARISE Study †
by
, , , ,
Kazuomi Ueshima
1,*, 
Naoshi Nishida
1
,
Satoru Hagiwara
1,
Yasunori Minami
1
,
Hiroshi Ida
1,
Masahiro Takita
1,
Hirokazu Chishina
1,
Masahiro Morita
1,
Tomoko Aoki
1
,
Tetsutaro Hamano
2,
Ryosuke Take
3,
Chizuko Watanabe
3,
Kohsuke Asoh
3,
Ai Tanaka
3 and
Masatoshi Kudo
1
1
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka 589-8511, Japan
2
P4 Statistics Co., Ltd., Tokyo 158-0082, Japan
3
Department of Oncology Medical Science, Chugai Pharmaceutical Co., Ltd., Tokyo 103-8324, Japan
*
Author to whom correspondence should be addressed.
†
The results of this study were presented as abstracts and posters: Ueshima, K.; Nishida, N.; Hagihara, S.; Minami, Y.; Ida, H.; Takita, M.; Chishina, H.; Morita, M.; Aoki, T.; Kudo, M. Retrospective study of the correlation between proteinuria and renal function in patients (pts) with unresectable hepatocellular carcinoma (uHCC) treated with atezolizumab plus bevacizumab (Atezo+Bev): ARISE study. ESMO Asia Congress 2023, Singapore, 1–3 December 2023; and Ueshima, K.; Nishida, N.; Minami, Y.; Ida, H.; Hagihara, S.; Takita, M.; Aoki, T.; Morita, M.; Kudo, M. No correlation between proteinuria and renal function in patients with unresectable hepatocellular carcinoma treated with atezolizumab + bevacizumab: ARISE study. In Proceedings of the 14th Annual Asia-Pacific Primary Liver Cancer Expert Association (APPLE) Congress 2024, Honolulu, HI, USA, 18–20 July 2024.
Cancers 2025, 17(23), 3826; https://doi.org/10.3390/cancers17233826 (registering DOI)
Submission received: 22 May 2025
/
Revised: 12 November 2025
/
Accepted: 22 November 2025
/
Published: 28 November 2025
(This article belongs to the Special Issue The Biology of Hepatocellular Carcinoma: Implications for Genomic and Immune Therapies (2nd Edition))
Simple Summary
Patients with unresectable hepatocellular carcinoma are often treated with atezolizumab and bevacizumab (Atezo + Bev). Proteinuria, a treatment-emergent adverse event caused by Bev, may force the suspension or discontinuation of Bev for safety reasons. In this study, we found that the urine protein level was not related to the deterioration of renal function in patients treated with Atezo + Bev. Accordingly, physicians should consider the risk–benefit profile when deciding whether to stop Bev in patients with above-normal urine protein levels during treatment with Atezo + Bev.
Abstract
Background: Atezolizumab plus bevacizumab (Atezo + Bev) is the standard of care for treatment-naïve patients with unresectable hepatocellular carcinoma (uHCC). Proteinuria is a treatment-emergent adverse event that often leads to Bev interruption. However, the relationship between Bev-related proteinuria and renal dysfunction is unclear. We retrospectively investigated the impact of proteinuria after starting Atezo + Bev on renal function in patients with uHCC. Methods: We performed a single-arm retrospective study of patients with uHCC treated with Atezo + Bev between 25 September 2020 and 31 May 2022, at Kindai University Hospital, Japan. The impact of proteinuria on renal function during Atezo + Bev treatment was analyzed in terms of the correlation between changes in urine protein creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) relative to baseline. Results: We analyzed data from 100 patients (median age 74 years; range 41–89; 75% male). During Atezo + Bev treatment, the median (interquartile range) maximum increase from baseline in UPCR was 0.39 (0.08 to 2.05) and the median maximum decline from baseline in eGFR was −7.5 (−20.5 to −3.0) mL/min/1.73 m2. The Pearson and Spearman correlation coefficients (95% confidence intervals) between these variables were −0.16 (−0.34 to 0.04) and −0.13 (−0.32 to 0.07), respectively. Conclusions: We found no correlation between the changes in UPCR and eGFR during Atezo + Bev treatment. Bev interruption criteria are based on the degree of proteinuria; however, our results suggest that proteinuria does not necessarily impair renal function. Physicians should consider the risk–benefit profile when deciding whether to discontinue Bev in patients who develop proteinuria during Atezo + Bev treatment.
