Albuminuria, Kidney Function, and Cancer Risk in the Community

Yejin Mok; Shoshana H. Ballew; Yingying Sang; Josef Coresh; Corinne E. Joshu; Elizabeth A. Platz; Kunihiro Matsushita

Disclosures

Am J Epidemiol. 2020;189(9):942-950. 

In This Article

Abstract and Introduction

Abstract

Few studies have comprehensively investigated the association of 2 key kidney disease measures, estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR), with cancer incidence. In 8,935 participants at the baseline (1996–1998) from the Atherosclerosis Risk in Communities study, we quantified the associations of eGFR (based on creatinine and cystatin C) and ACR with cancer risk using Cox regression models adjusted for potential confounders. Due to changing guidelines for prostate cancer screening during the follow-up period, we investigated overall cancer, overall nonprostate cancer, and site-specific cancer. During a median follow-up of 14.7 years, 2,030 incident cancer cases occurred. In demographically adjusted models, low eGFR and high ACR were associated with cancer incidence (both overall and overall nonprostate cancer). These associations were attenuated after adjusting for other shared risk factors, with a significant association remaining only for ACR (≥103 compared with 5 mg/g) and overall nonprostate cancer. For site-specific cancer, only high ACR showed a significant association with lung and urinary tract cancers. Of these, the association between ACR and lung cancer appeared most robust in several sensitivity analyses. Kidney disease measures, particularly high ACR, were independently associated with cancer risk. The association between ACR and lung cancer was uniquely robust, warranting future studies to explore potential mechanisms.

Introduction

Chronic kidney disease (CKD), usually defined as reduced glomerular filtration rate (GFR) or elevated albuminuria, is a major and growing global public health problem.[1] CKD has been shown to contribute to a broad range of adverse outcomes, such as cardiovascular disease,[2,3] infections,[4] metabolic and endocrine disorders,[5,6] frailty,[7] and cognitive impairment.[8]

Recently, a few studies suggested that individuals with CKD have a higher risk of cancer,[9–17] but other studies have yielded conflicting results.[12,18–23] Due to different definitions of CKD (only reduced estimated GFR (eGFR),[9–11,14,15,19–21,23] only elevated albuminuria,[16–18] or a combination[13,22]) in previous studies, it is hard to derive common conclusions. Moreover, most of previous studies relied on semiquantitative dipstick proteinuria as a measure of albuminuria[12–14,22] and explored creatinine-based eGFR[9–15,19–23] despite eGFR using 2 filtration markers, serum creatinine and cystatin C, being considered the best estimate of measured GFR.[24] Also, comprehensive delineation of potential confounders was not consistently available in previous studies. This is important because demographic versus extended adjustment will have different implications, with the former for cancer screening (often age and sex are key determinants of screening eligibility) and the latter for etiological contributions of CKD.

To address limitations of prior studies, we aimed to comprehensively assess whether both measures of CKD, eGFR based on serum creatinine and cystatin C and urine albumin-to-creatinine ratio (ACR), were independently associated with overall and site-specific cancer incidence and mortality in a community-based cohort study.

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