Common Blood Protein Predicts Kidney Disease

A common protein in the blood can reliably predict a person's risk of developing chronic kidney disease (CKD) years before symptoms develop, according to a study published Nov. 12 in the New England Journal of Medicine. Researchers believe the marker—soluble urokinase-type plasminogen activator receptor (suPAR)— will be used in the near future as a screening test, much like cholesterol, to identify at-risk patients who can make lifestyle changes to ward off development of CKD.

Currently two markers—estimated glomerular filtration rate (eGFR; based on measuring blood creatinine) and proteinuria—are used to monitor CKD, but they are not sensitive enough to detect the disease in its earliest stages.

"For the last century, doctors have relied on creatinine levels and urine protein levels to detect and monitor kidney disease," said lead author Salim Hayek, M.D., from the Emory Clinical Cardiovascular Research Institute in Atlanta. "These markers are useful in diagnosing kidney disease, but are not helpful in predicting whether a person might develop disease in the future. We need to find a way to identify those at risk, in order to prevent the disease or catch it in its early stages."

Severe organ damage can occur with CKD before symptoms even develop and it is a costly problem. Medicare, the authors say, spent $87 billion on kidney disease in 2012. CKD affects more than 15 percent of U.S. adults, with an estimated 4 percent requiring dialysis or transplant due to organ failure from disease progression.

In the NEJM study, 2,292 patients' samples were used to measure suPAR and eGFR at baseline and then again after five years of follow-up. The patients (average age 63 years) were part of a cohort who underwent cardiac catheterization between 2003 and 2009. suPAR levels were classified into four quartiles.

The researchers found that 320 participants (24 percent) developed CKD during follow-up. A higher suPAR level at baseline was associated with a significantly greater incidence of CKD at follow-up. Among participants with high suPAR levels (greater than 3,040 ng/mL) but normal eGFR levels at baseline, 40 percent developed CKD over the five years. But only 10 percent of those with low suPAR levels (below 2,373 pg/mL) at baseline developed the disease. Additionally, suPAR predicted eGFR decline (a sign of CKD progression) in patients with CKD at baseline, regardless of their age, gender or race.

The researchers say that suPAR seems to be a more powerful predictor of CKD than other previously known risk factors, including race and the APOL1 risk gene. When suPAR level was included in a model based on conventional risk factors, the change in risk was larger than that with all other variables combined.

"SuPAR promises to do for kidney disease what cholesterol has done for cardiovascular disease," said senior author Jochen Reiser, M.D., Ph.D., from Rush University Medical Center in Chicago, in a statement.

The researchers replicated results in a second patient cohort—participants in the Women's Interagency HIV Study. After controlling for HIV, which is known to elevate suPAR, the researchers confirmed that high suPAR levels predict decline in kidney function, although at a slower rate than in the Emory cohort.

"suPAR remained associated with a decline in renal function among younger persons, who have a significantly lower burden of risk factors for cardiovascular disease, which suggests that the effect of suPAR is truly independent of traditional risk factors for cardiovascular disease and CKD," the authors write.

Takeaway: suPAR appears to be a robust marker of CKD risk. Researchers believe it will quickly be incorporated into preventive care, much like cholesterol screening.