Researchers who investigated the level of kidney function and subsequent cancer risk in more than one million adults have found that reduced glomerular filtration rate (GFR) — a key measure of reduced kidney function and chronic kidney disease — is an independent risk factor for renal and urothelial cancer.
The retrospective study of almost 1.2 million adult members of the Kaiser Permanente Northern California healthcare system was conducted by the Kaiser Permanente Division of Research, the University of Utah’s Huntsman Cancer Institute and Memorial Sloan-Kettering Cancer Center, and published online today in the Journal of the American Society of Nephrology.
Chronic kidney disease and cancer are both major and growing public health problems. The incidence of chronic kidney disease continues to rise, with an estimated 11.5 percent of the U.S. population having reduced glomerular filtration rate, and approximately 13.5 million Americans with stage 3 or worse chronic kidney disease.
“While multiple studies have observed higher risks of cancer in persons with end-stage renal disease, the association of less severe kidney disease with cancer remains poorly understood,” said senior author Alan S. Go, MD, of the Kaiser Permanente Division of Research. “These findings address that knowledge gap.”
Investigators studied 1,190,538 adults aged 40 years and older with known kidney function and no history of cancer, dialysis or renal transplantation. Median follow-up of the cohort between 2000 and 2008 was 5.3 years. At their entry point to the study, patients with lower GFR were more likely to be older, be persons of color, be current or former smokers, have lower socioeconomic status, and have a higher burden of comorbidity.
Glomerular filtration rates are calculations that indicate how well one’s kidneys are filtering blood. A glomerular filtration rate of 60 to 89 is considered to be within the normal range unless there is other evidence of kidney disease, whereas a glomerular filtration rate of 45 to 59 indicates moderate kidney disease, and a glomerular filtration rate of less than 30 indicates severe chronic kidney disease.
During follow-up, a total of 76,809 cases of cancer were documented among 72,875 patients. When comparing glomerular filtration rates of 60 to 89, researchers found:
- A 39 percent increased rate of renal cancer when patients' glomerular filtration rate was 45 to 59.
- A 100 percent increased rate of renal cancer when patients’ glomerular filtration rate was less than 30.
Compared with GFR of 60 to 89, researchers also found that GFR less than 30 was associated with a 48 percent increased rate of urothelial cancer. However, GFR levels below 60 were not significantly associated with prostate, colorectal, lung, breast or any other cancer.
The researchers say several possible biologic mechanisms may help to explain the association between level of kidney function and renal or urothelial cancers. Kidney dysfunction results in a state of chronic inflammation and oxidative stress, and such an inflammatory microenvironment may play a role in cancer development. Severe chronic kidney disease may additionally create a relative state of immunodeficiency, which could influence the development of cancer.
“These and other mechanisms deserve further study in order to better define the link between kidney function and site-specific cancer risk,” said lead author William T. Lowrance, MD, MPH, investigator at the Huntsman Cancer Institute. “The stronger association of reduced glomerular filtration rate and clear cell renal cancer as compared with non-clear cell may provide new insights into the biologic underpinnings of the association of chronic kidney disease and renal cancer.”
“These findings could have clinical implications for directing cancer screening efforts in select populations,” said Juan Ordonez, MD, study co-author and Chair of the Chiefs of Nephrology for Kaiser Permanente Northern California. “Currently, there are no evidence-based cancer screening recommendations tailored for patients with chronic kidney disease. Additional studies are needed to clarify the reasons for this association and help us assess the potential advantage of targeted cancer screening in patients with chronic kidney disease.”
Additional authors of the study are Paul Russo, MD, FACS, of Memorial Sloan Kettering, and Natalia Udaltsova, PhD, of the Kaiser Permanente Division of Research.
This research was supported by National Institutes of Health [T32-CA82088] and by the National Institute of Diabetes, Digestive and Kidney Diseases [U01 DK060902].