Proteins tied to kidney failure: research could lead to predictive test for diabetics.

A simple blood test might reveal which people with diabetes are most prone to kidney failure, two long-term studies show. Both studies linked high levels of proteins called tumor necrosis factor, or 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.

"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."

In one study, the researchers tracked the health status of 410 people with type 2 diabetes beginning in the early 1990s. Patients provided initial blood samples followed by information on their health over the next eight to 12 years. By the end of the study's follow-up period, 54 percent of patients with high concentrations of TNF receptors at the outset had developed kidney failure and needed dialysis or a transplant. Only 3 percent of patients with low levels of TNF receptors had such problems. 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.

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."

Kidney failure causes
In 2008, 112,476 people in the
United States began treatment
for end-stage renal disease
(causes shown below).

Diabetes               44%

High blood pressure    28%

Other causes           19%

Glomerular disease      7%

Cystic kidney disease   2%

SOURCE: NATIONAL KIDNEY AND UROLOGIC
DISEASES INFORMATION CLEARINGHOUSE

Note: Table made from pie chart.