Common protein in blood rises years before disease develops
By Maggie Van Dyke
Make room, cholesterol. A new disease indicator is entering the medical vocabulary: suPAR, a circulating protein that a simple blood test can measure. Researchers have found that suPAR reliably can predict a healthy person’s chances of developing chronic kidney disease as much as five years before this stealthy killer starts causing damage.
“SuPAR promises to do for kidney disease what cholesterol has done for cardiovascular disease,” says Jochen Reiser, MD, PhD, chairperson of the Department of Internal Medicine and Ralph C. Brown MD Professor of Medicine at Rush University Medical Center. Reiser is senior author of an article published in the Nov. 5 online issue of the New England Journal of Medicine that reports the findings about suPAR, which stands for soluble urokinase-type plasminogen activator receptor.
He believes that in the near future, high suPAR levels probably will inform physician-patient conversations about preventing kidney disease, just as high cholesterol levels signal the need for lifestyle changes and protective drugs to avert heart attacks and strokes.
Such interventions cold make an enormous impact on the health of the tens of millions of people in the U.S. who have chronic kidney disease — a progressive failure of function that prevents kidneys from fulfilling their role filtering waste from the blood stream. More than 15 percent of people in the U.S. have chronic kidney disease, and approximately four percent require dialysis and/or a kidney transplant due to kidney failure.
In addition to reducing unnecessary deaths and improving quality of life, a significant decrease in kidney disease incidence would dramatically cut health care spending. In 2012, Medicare alone spent $87 billion on medical care provided to patients with chronic and end-stage kidney disease.
Looking for a better disease marker
Chronic kidney disease causes about 47,000 deaths a year and is known as a silent killer, because most people don’t realize they have it until the disease is well advanced. Chronic kidney disease often causes severe organ damage before symptoms — such as blood in the urine, swollen hands and feet, and excessive thirst — develop.
In the advanced phases, patients develop serious complications, including high blood pressure, and eventually the kidneys may fail. However, because the heart works very intimately with the kidneys, most people with kidney disease die of heart problems before their kidneys give out.
Currently, physicians rely on two markers to detect and manage chronic kidney disease:
- Estimated glomerular filtration rate (eGFR), based on measuring creatinine in the blood, indicates how well the kidneys filter waste
- Proteinuria, or high protein levels in urine
While these disease indicators are very helpful in monitoring existing kidney disease, they are not sensitive enough to catch the disease in its early stages or to predict a person’s risk of developing the disease.
That shortcoming is what makes the study findings in the NEJM so important. It found a high suPAR level to be an excellent predictor of future kidney disease.
The researchers measured suPAR levels and kidney function (based on eGFR rates) in 2,292 people at baseline and again at follow up. Of these subjects, 40 percent with high suPAR levels (greater than 3,040 ng/mL) but no known kidney disease (i.e., healthy eGFR levels) went on to develop chronic kidney disease over the course of five years. In comparison, only 10 percent of those with low suPAR levels at baseline developed the disease.
“We can now risk-stratify people according to their potential to develop kidney disease using suPAR levels,” explains Salim Hayek, MD, first author of the study and fellow at the Emory Clinical Cardiovascular Research Institute.
Reiser and his Rush colleagues collaborated on the National Institutes of Health-funded study with researchers at Emory Clinical Cardiovascular Research Institute, Harvard Medical School, NYU Langone Medical Center, and John H. Stroger, Jr. Hospital of Cook County.
Trumping other risk factors
Another important finding from the study is that suPAR seems to be a more powerful predictor of chronic kidney disease than other previously known high risk factors. For instance, blacks are known to have a higher risk of the disease than whites, which is explained in part by the discovery that people of African dissent are more likely to carry the APOL1 gene, which increases kidney disease risk.
“What we’ve shown is that it doesn’t matter whether our subjects were black or white. SuPAR was a strong independent predictor of eGFR decline. APOL1 is still a genetic risk factor for renal disease in the black population, but suPAR’s power to predict renal disease appeared not be majorly different in black or white patients,” said Sanja Sever, PhD, assistant professor of medicine at Massachusetts General Hospital and the study’s co-first author.
Reiser is also excited by the study’s finding related to diabetes. While diabetes is the number one cause of chronic kidney disease, only about one-third of patients with diabetes develop diabetic kidney disease.
“Today, nobody knows which patients with diabetes will get the disease,” Reiser observes. “In our paper, we show that among patients with diabetes, the ones with elevated suPAR at baseline were more likely to develop kidney disease. This finding will help risk-stratify specifically patients with diabetes on their risk of future kidney disease.”
Anticipating suPAR blood tests and developing novel treatments
In the near future, Reiser anticipates that many healthcare providers will start measuring patients’ suPAR levels on a regular basis to detect kidney risk, just as they measure cholesterol and blood pressure levels to predict heart disease.
The suPAR tests used in the study have not been approved for general patient care by the U.S. Food and Drug Administration. However, Reiser believes momentum will build for FDA approval of the tests, which are inexpensive. In addition to being an indicator of future kidney disease, high suPAR levels have been found to be associated with severe sepsis, cardiovascular disease, and other serious health problems.
Once physicians know which patients have high suPAR levels, doctors can counsel people at risk about ways to lower their chance of developing chronic kidney disease. Many of the same lifestyle issues that lead to heart disease also cause suPAR levels to rise: smoking, an unhealthy diet, and being overweight/obese.
“One characteristic of suPAR is that it is modifiable to some degree by lifestyle,” Reiser says. “Also, if suPAR is high, we can be more aggressive in terms of giving medications to control high blood pressure and diabetes, which contribute to chronic kidney disease.”