Kidney Function and Risk of Renal Cell Carcinoma

Author:

Alcala Karine1ORCID,Zahed Hana1ORCID,Cortez Cardoso Penha Ricardo1ORCID,Alcala Nicolas1ORCID,Robbins Hilary A.1ORCID,Smith-Byrne Karl2ORCID,Martin Richard M.345ORCID,Muller David C.6ORCID,Brennan Paul1ORCID,Johansson Mattias1ORCID

Affiliation:

1. 1Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.

2. 2Cancer Epidemiology Unit, Oxford Population Health, University of Oxford, Oxford, United Kingdom.

3. 3Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.

4. 4NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, United Kingdom.

5. 5Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.

6. 6Imperial College London, London, United Kingdom.

Abstract

Abstract Background: We evaluated the temporal association between kidney function, assessed by estimated glomerular filtration rate (eGFR), and the risk of incident renal cell carcinoma (RCC). We also evaluated whether eGFR could improve RCC risk discrimination beyond established risk factors. Methods: We analyzed the UK Biobank cohort, including 463,178 participants of whom 1,447 were diagnosed with RCC during 5,696,963 person-years of follow-up. We evaluated the temporal association between eGFR and RCC risk using flexible parametric survival models, adjusted for C-reactive protein and RCC risk factors. eGFR was calculated from creatinine and cystatin C levels. Results: Lower eGFR, an indication of poor kidney function, was associated with higher RCC risk when measured up to 5 years prior to diagnosis. The RCC HR per SD decrease in eGFR when measured 1 year before diagnosis was 1.26 [95% confidence interval (95% CI), 1.16–1.37], and 1.11 (95% CI, 1.05–1.17) when measured 5 years before diagnosis. Adding eGFR to the RCC risk model provided a small improvement in risk discrimination 1 year before diagnosis with an AUC of 0.73 (95% CI, 0.67–0.84) compared with the published model (0.69; 95% CI, 0.63–0.79). Conclusions: This study demonstrated that kidney function markers are associated with RCC risk, but the nature of these associations are consistent with reversed causality. Markers of kidney function provided limited improvements in RCC risk discrimination beyond established risk factors. Impact: eGFR may be of potential use to identify individuals in the extremes of the risk distribution.

Funder

Cancer Research UK

NIHR Bristol Biomedical Research Centre

Medical Research Council

National Institute for Health and Care Research

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology,Epidemiology

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