#970 The impact of VEGF signalling pathway inhibitors and/or immune checkpoint inhibitors on kidney function over time
Authors: Elyan Benjamin , Hedley James , Sullivan Michael , De La Mata Nicole , Webster Angela , Venugopal Balaji , Jones Rob , Lang Ninian , Mark Patrick , Lees Jennifer 
Published: May 2024

Abstract

Background and Aims
Treatment with vascular endothelial growth factor signalling pathway inhibitors (VSPI) and immune checkpoint inhibitors (ICI) has transformed outcomes in advanced kidney cancer. VSPI and ICI can both independently cause side effects that are risk factors for development or progression of chronic kidney disease (CKD). We analysed estimated glomerular filtration rate (eGFR) decline in people with kidney cancer following treatment with VSPI or ICI.

Methods
We linked routine healthcare databases in the West of Scotland, UK (spanning 2010–2020, population 1.4 million) to identify adults with advanced kidney cancer who received a VSPI and/or ICI. In the two years following therapy initiation, eGFR slope (defined as annualised rate of change in eGFR) was modelled using linear mixed-effects models for the whole group and subgroups of people who had nephrectomy, metastatic cancer and a baseline eGFR &lt;60 mL/min/1.73 m² prior to systemic therapy. Additional outcomes were studied using competing risk regression considering the competing risk of death: 40% decline in eGFR, de-novo proteinuria (urine albumin creatinine ratio &gt;3 mg/mmol), and progression to eGFR &lt;15 mL/min/1.73 m2. The risk of all-cause mortality was estimated with Cox regression models.

Results
We studied 357 adults (62.5% male; median age 63.0 years, IQI 55.0-71.0) with kidney cancer who were treated with either VSPI and/or ICI. The median baseline eGFR before systemic therapy was 74.6 mL/min/1.73 m² (58.3-91.9) and most received VSPI monotherapy (86.0%). On average, eGFR remained relatively stable over time (average annual increase +1.03 mL/min/1.73 m²/year: 95% CI −1.64 to +3.70, p = 0.2). People who had nephrectomy prior to systemic therapy demonstrated the largest average increase in eGFR (+2.30 mL/min/1.73 m²/year: 95% CI −1.66 to + 6.26). People with baseline eGFR &lt;60 mL/min/1.73 m² prior to systemic therapy had a small decline (−1.02 mL/min/1.73 m²/year: 95% CI −6.55 to +4.50) in eGFR (Fig. 1). A ≥40% decline in eGFR occurred in 82 people (23.0%) within one year of starting systemic therapy. People with diabetes were more likely to experience a ≥40% decline in eGFR (subdistribution HR 1.89: 95% CI 1.05-3.41, p = 0.04). A decline in eGFR to &lt;15 mL/min/1.73 m² or kidney failure with replacement therapy was found in 4 (1.1%) people. Among the 75 people assessed for proteinuria, 30.2% developed de-novo microalbuminuria. Median overall survival was 1.36 years (IQI 1.11-1.75 years), but this was longer in people who had nephrectomy prior to systemic therapy: 2.13 years (IQI 1.82–2.57 years). A 40% acute or chronic decline in eGFR was not associated with increased hazards of death on univariable or multivariable analysis (adjusted HR: 1.11: 95% CI 0.85-1.46, p = 0.4).

Conclusion
Despite case series and prescribing guidelines highlighting adverse impact of VSPI/ICI therapy on kidney function, our results demonstrate that there is no significant impact on the average change in eGFR but highlights that people with diabetes are at higher risk of clinically significant renal events. With appropriate monitoring, more widespread use of these agents in patients with renal impairment may be warranted.