Proteins may warn of diabetic kidney disease risk

Levels of a natural compound in blood seem to foreshadow high risk of renal failure

A simple blood test might reveal which people with diabetes are most prone to kidney failure, two long-term studies show. An abundance of two compounds better known as culprits in inflammation seems to pinpoint high-risk diabetes patients years before they show outward signs of kidney problems, researchers say.

Both studies linked high levels of proteins called tumor necrosis factor (TNF) receptors with elevated incidence of kidney disease up to 12 years later. The association showed up in patients with type 1 and type 2 diabetes, the researchers report online January 19 in the Journal of the American Society of Nephrology.

Study leader Andrzej Krolewski, a kidney researcher at Harvard Medical School and the Joslin Diabetes Center in Boston, says the findings may ultimately improve care for at-risk diabetes patients. “The most immediate application,” says study coauthor Monika Niewczas, a researcher also at Harvard and Joslin, “will be a diagnostic test that we hope would be available soon.”

TNF receptors serve as docking stations on cells. When their counterpart protein latches onto the receptor, the signal produced by that binding can instruct a cell to trigger inflammation or to take on other duties. Some TNF receptors also roam free, showing up in the blood, a characteristic the scientists measured in the new studies.

In one study, the researchers tracked the health status of 410 people with type 2 diabetes in the early 1990s. Patients provided initial blood samples followed by information on their health over the subsequent eight to 12 years. By the end of the study’s follow-up period, 54 percent of the patients with high concentrations of TNF receptors in that initial blood sample had developed kidney failure and needed dialysis or a transplant, whereas only 3 percent of patients with low levels of TNF receptors did. After accounting for differences among the patients, the high-receptor group was still about six times more prone to kidney failure, Niewczas says.

The other study included 628 patients with type 1 diabetes, formerly called juvenile-onset diabetes. Over five to 12 years of follow-up, participants who had high TNF receptor levels at the start were three times as likely to develop chronic kidney disease as those with low receptor levels.

“These are good pilot studies, very well conducted,” says Sankar Navaneethan, a nephrologist at the Cleveland Clinic, who wasn’t involved in the new research. “But they need to be replicated in future studies before we can embark on using this biomarker for predicting these outcomes in patients.”

Diabetes is the most common cause of kidney failure, accounting for 44 percent of new cases in 2008. Chronic inflammation has long been suspected in this connection, but the Joslin team reports that several common inflammatory proteins don’t show a link to kidney disease — only the TNF receptors do.

The researchers “provide very solid statistical and epidemiological evidence” linking TNF receptor abundance with kidney damage, says Klaus Ley, a physician at the La Jolla Institute for Allergy and Immunology in California. “But we don’t know why the receptor levels are increased in these patients. This is just the beginning of a very exciting story.”

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