Chronic Kidney Disease Associated With Increased Risk of Renal and Urothelial Cancers

Will Lowrance, MD, MPH

Assistant Professor, Surgery

Huntsman Cancer Institute

at the University of Utah

Does renal disease increase one’s risk of developing cancer? We know there is a well-studied association between end-stage renal disease and cancer risk, but whether or not less severe forms of kidney disease place patients at an increased risk for various cancers is uncertain. A recent study from Huntsman Cancer Institute (HCI) at the University of Utah, Kaiser Permanente Division of Research, and Memorial Sloan Kettering Cancer Center (MSKCC) has shed some new light on this question. The researchers found that people with reduced renal function or chronic kidney disease were at an increased risk of renal and urothelial cancer but not at higher risk for other specific cancer types.¹

These findings are interesting, especially if one considers that both chronic kidney disease and cancer are major public health issues in the United States. Over 11% of the US population is estimated to have some level of chronic kidney disease. More than 13 million Americans are thought to have at least stage III chronic kidney disease, defined as an estimated glomerular filtration rate (GFR) of less than 60 ml/ min/1.73m². Likewise, cancer remains one of the primary causes of morbidity and mortality in the United States, and it is projected there will be over 1.6 million new cancer cases diagnosed and over 585,000 cancer deaths in the United States during 2014.²

Investigators from the University of Utah’s HCI, MSKCC, and Kaiser Permanente retrospectively studied nearly 1.2 million adults with known renal function and recently published their results in the Journal of the American Society of Nephrology.¹

During 6,000,420 person years of follow-up, 76,809 new cancers were diagnosed within the cohort. After adjusting for potential confounders (age, race, sex, income, education, smoking, BMI, comorbidities, medications, health care utilization, hematuria, and imaging utilization) we found that lower estimated GFR was associated with an increased risk of kidney cancer. (HR = 1.39; 95% CI, 1.22-1.58 for estimated GFR = 45-59; HR = 1.81; 95% CI, 1.51-2.17 for estimated GFR = 30-44; HR = 2.28; 95% CI, 1.78-2.92 for estimated GFR <30).

This increased risk of renal cancer was greater for conventional clear cell renal cancer as compared with non-clear cell renal cancers. Additionally, an increased risk of urothelial cancer was found for estimated GFR <30 but no significant associations between lower renal function and prostate, breast, lung, colorectal, or all cancers combined.

The researchers went to great lengths to attempt to control for variables that may confound the relationship of renal function and cancer risk. A broad list of potential confounding variables was incorporated into the extended Cox regression models to better delineate the independent association of renal function and incident cancer risk. Furthermore, any cancer diagnoses during the first two years of follow-up and any estimated GFR measurements performed within three months of the cancer diagnosis were excluded from the final models.

Underlying biologic mechanisms for the association between chronic kidney disease and renal or urothelial cancers are not fully understood, but several possible explanations exist. Chronic kidney disease can result in a state of inflammation, oxidative stress, or even immunodeficiency, thus leading to an inflammatory microenvironment that could impact cancer development.

More research is needed to further delineate the physiologic mechanism underlying the association between renal function and renal or urothelial cancer risk.

Clinically, this research may help to inform the debate about whether or not patients with chronic kidney disease should have some sort of targeted cancer screening. If the results of this research are corroborated, then it may have implications for directing cancer screening efforts in selective populations of patients with chronic kidney disease.

References

1. Lowrance WT, Ordonez J, Udaltsova N, Russo P, Go AS. CKD and the risk of incident cancer [published online May 29, 2014]. J Am Soc Nephrol. doi:10.1681/ ASN.2013060604.
2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9-29.