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Extra risk in kidney disease

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There are plenty of good reasons to take care of your kidneys -- no one really wants to go on dialysis or get a transplant. Poorly functioning kidneys also increase your chances of developing -- and dying from -- cardiovascular disease. Now, a study suggests that even moderate kidney disease increases the risk for men to develop certain cancers.

Chronic kidney disease affects 26 million adults in the U.S., and the numbers are on the rise. In 1994, 10% of adult Americans had the disease, but by 2004, that number had risen to 13%, according to data collected by the Centers for Disease Control and Prevention. This increase probably results from the fact that people are living longer -- age is a risk factor for kidney disease -- and more people have diabetes and hypertension, two big contributors to kidney disease.

Previous research has shown that cancer occurs at a higher than normal rate in kidney transplant patients. Australian researchers wondered whether the risk for developing cancer starts earlier in the progression of kidney disease. “We hypothesized that it doesn’t occur spontaneously in the end stage,” says Dr. Germaine Wong, a research fellow at the University of Sydney in Australia.

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The new study, published April 30 in the Journal of the American Society of Nephrology, used data collected from a study population of 3,654 adults in Australia. Over 10 years, 711 study subjects developed cancer and researchers associated that outcome with a key measure of kidney function that was measured at the beginning of the study.

That measure, the glomerular filtration rate (GFR), is derived from a blood test for creatinine. The kidney’s job is to filter the blood and process what it filters, deciding what stays in the body and what goes out via urine, says Dr. Anton Schoolwerth, a nephrologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., who has written about chronic kidney disease as a public health threat. When kidney function is below optimal levels, the GFR decreases, which leads to a rise in serum creatinine.

Men whose GFRs were less than 55 -- what the study authors describe as moderate disease -- had a 39% higher risk of developing cancer than those with normal kidney function, and men with GFRs of less than 40 -- more significant disease -- had a 300% increased risk.

“You think of a doubling of risk as being really big. That’s a tripling,” says Dr. Neil Powe, chief of medical services at San Francisco General Hospital and a trained epidemiologist.

Kidney disease did not increase risk for all cancers or all subjects. Cancers of the lung and bladder -- but not the prostate -- showed an association with chronic kidney disease in men. No increased risk for any cancer was found in women. Explanations for these observations await further research.

Powe says the strengths of the study were how many people were included and how long they were followed. The fact that cancer risk increased in a stepwise fashion as kidney function worsened is particularly compelling to researchers because it suggests a close link between the two.

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However, observational studies by their nature only measure an association between two outcomes -- they cannot prove cause and effect. For instance, some yet-to-be-unidentified factor may be causing kidney disease and cancer in the rather homogenous study population.

The study group was “90% white Caucasian Australians living in West Sydney,” says Wong, who hopes to extend her group’s findings to larger and more diverse populations in the future. Powe agrees, noting that chronic kidney disease is more common in certain racial and ethnic groups, such as African Americans and Latinos.

Doctors diagnose kidney disease based on GFR in addition to visible evidence of kidney damage -- via CT scans and ultrasound -- or protein in the urine. Severity of disease is rated on a five-stage scale with Stage 5 representing kidney failure, defined as a GFR less than 15. The association with cancer was observed in study subjects with Stage 3 disease, with GFRs between 30 and 59. According to the CDC, 5.4% of American adults have Stage 3 kidney disease, but only about 8% of them are aware of it.

Indeed, nephrologists and public health researchers consider kidney disease to be a silent killer, a phrase more commonly used for cardiovascular disease because the most important warning sign -- elevated blood pressure -- comes without symptoms. Likewise, reduced GFR is the best indicator of declining kidney function but often occurs without obvious symptoms, although people may experience fatigue, swollen feet, poor appetite and frequent urination when their kidney function is poor.

Most people probably don’t know what their GFR is. Testing for serum creatinine is simple but not standard. Your doctor should order the test if you’re in a high-risk group for kidney disease -- that is, if you have diabetes or hypertension, if you are over 60 or if you have a family history of the disease. Schoolwerth is working with CDC researchers on a cost-benefit assessment of universal GFR screening.

The linkage of moderate kidney disease with cancer, if it holds up with further study, may tip the balance to wider testing. “It’s another piece of information that means we’ve got to be alert in picking these people up,” Schoolwerth says.

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health@latimes.com

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