OAKLAND, Calif. — A key measure of reduced kidney function and chronic kidney disease — reduced glomerular filtration rate — is an independent risk factor for renal and urothelial cancer, according to a study 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/or proteinuria, a condition in which a person has an abnormal amount of protein in the blood and a sign often associated with kidney disease. Approximately 13.5 million Americans with advanced stages of chronic kidney disease.

Researchers from Kaiser Permanente, Huntsman Cancer Institute, and Memorial Sloan Kettering Cancer Center examined the medical records of nearly 1.2 million adult members of Kaiser Permanente in Northern California who were 40 years of age and older, with known kidney function and no history of cancer, dialysis or renal transplantation. At their entry point to the study, patients with lower glomerular filtration rates were more likely to be older, be persons of color, be current or former smokers, have lower socioeconomic status, and have other chronic diseases.

"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."

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.
• A 48 percent increased rate of urothelial cancer when patients' glomerular filtration rate was less than 30.

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 such an inflammatory microenvironment may play a role in cancer development," said senior author Alan S. Go, senior investigator at the Kaiser Permanente Northern California Division of Research. "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 University of Utah's Huntsman Cancer Institute. "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 Cancer Center, 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].

About the Kaiser Permanente Division of Research

The Kaiser Permanente Division of Research conducts, publishes and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and the society at large. It seeks to understand the determinants of illness and well-being and to improve the quality and cost-effectiveness of health care. Currently, the Division's 550+ staff are working on more than 350 ongoing research studies in behavioral health and aging, cancer, cardiovascular and metabolic conditions, health care delivery and policy, infectious diseases, vaccine safety and effectiveness, and women's and children's health. For more information, visit http://www.dor.kaiser.org/.

About Kaiser Permanente

Kaiser Permanente is committed to helping shape the future of health care. We are recognized as one of America's leading health care providers and not-for-profit health plans. Founded in 1945, our mission is to provide high-qukp.org/shareality, affordable health care services and to improve the health of our members and the communities we serve. We currently serve approximately 9.1 million members in eight states and the District of Columbia. Care for members and patients is focused on their total health and guided by their personal physicians, specialists and team of caregivers. Our expert and caring medical teams are empowered and supported by industry-leading technology advances and tools for health promotion, disease prevention, state-of-the-art care delivery and world-class chronic disease management. Kaiser Permanente is dedicated to care innovations, clinical research, health education and the support of community health. For more information, go to kp.org/share.