Study: Cancer Is a Major Cause of Mortality in Some Chronic Kidney Disease Patients

By Joseph Nally, MD

For many years, nephrologists have been aware of the importance of monitoring chronic kidney disease (CKD) patients for cardiovascular disease and its risk factors. However, a new study shows that for some non-dialysis-dependent CKD patients, cancer also is a major cause of mortality. For some patients, it actually poses a greater risk than does cardiovascular disease.

These findings are derived from a retrospective review of approximately 39,000 CKD patient records led by researchers in the Department of Nephrology and Hypertension in Cleveland Clinic’s Glickman Urological & Kidney Institute.

The study found that the two leading causes of mortality were heart disease, in about 35 percent of patients, and cancer, in about 32 percent. These two causes account for two-thirds of deaths in these patients, a higher rate than in the general population.

This study is groundbreaking, as it is the first time that cause-specific mortality in patients with non-dialysis-dependent CKD has been reported in the United States.

The association between low glomerular filtration rate (GFR) and an elevated risk of death, cardiovascular events and hospitalization has been known for more than a decade, but no one has actually examined the specific causes of death. The renal community believed that cardiovascular death rates would be much more pronounced than what our data showed. Many experts in the field predicted that heart disease might account for considerably more than 50 percent of the deaths.

Two Key Findings

We reviewed the records of 33,478 white and 5,042 black patients with CKD who lived in Ohio between January 2005 and September 2009. The mean patient age was 72.8 ± 11.8 years. Fifty-six percent of patients were female. A total of 6,661 patients died during the study’s time frame.

The registry’s highly detailed information on aspects such as demographics and comorbidities enabled us to make two key findings, with implications for screening and disease management.

One is that there are more cancer deaths than cardiovascular-related ones in patients who have mild kidney disease — that is, those with a GFR of 45 to 59. But as kidney function decreases and a patient’s GFR falls below 30, there are twice as many deaths from heart disease than from cancer ‒ 39.6 percent versus 20 percent, respectively. This is the first time it has been shown that with mild kidney disease, more people died of cancer than of heart disease.

The second important finding was that both black and white CKD patients have the same mortality rates when the data are fully adjusted for all other comorbid diseases. However, black patients die more often from cardiovascular disease than from malignancy overall.

Implications for Screening

The key message of these findings is that while nephrologists and others caring for CKD patients need to maintain an emphasis on cardiovascular risk management, they also must be vigilant about screening patients with mild kidney disease for cancer.

No one type of cancer was found to be more common than another. All of the usual cancers were represented, such as colon, breast and lung. The risk was spread across the board.

Our findings also illustrate the need for better monitoring and management of heart disease risk in black CKD patients. Further studies should be undertaken to determine the mechanisms underlying these patients’ higher rates of cardiovascular-related mortality.

A Valuable Data Source

There is another important message to be learned from this research. Previous cause-specific mortality research utilized the Social Security Death Index as the gold standard. Due to changes in health privacy laws, as well as political considerations, that information has not been available since November 2011.

The new standard became the National Death Index, which requires a fee for its information. This severely restricts researchers’ ability to access these data.

However, our team learned in the course of its work that the National Death Index gathers its information from all 50 states. Colleagues in Cleveland Clinic’s Quantitative Health Sciences group, notably Jesse Schold, PhD, and Susana Arrigain, MA, found that they could access Ohio Death Index information free of charge, and that it provides cause-specific deaths.

Our team validated the Ohio Death Index against Cleveland Clinic’s electronic medical records and other sources, so we knew it was accurate.

Working with the Ohio Death Index allowed our team to produce this significant manuscript exploring cause-specific deaths from CKD. This is an important lesson and we encourage other researchers to explore whether their states’ death indexes are as accessible as Ohio’s.

Dr. Nally is the Director of the Center for Chronic Kidney Disease and a staff member of the Department of Nephrology and Hypertension in Cleveland Clinic’s Glickman Urological & Kidney Institute. He is also a staff member of the Transplant Center and a Clinical Professor of Medicine at Cleveland Clinic Lerner College of Medicine.