In a new study entitled “Soluble Urokinase Receptor and Chronic Kidney Disease,” researchers discovered that measuring levels of a protein circulating in our blood – suPAR, or soluble urokinase-type plasminogen activator receptor – can predict the likelihood of developing chronic kidney disease up to five years before other standard markers. The study was published in the New England Journal of Medicine.
“SuPAR promises to do for kidney disease what cholesterol has done for cardiovascular disease. One characteristic of suPAR is that it is modifiable to some degree by lifestyle. 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,” said Jochen Reiser, MD, PhD, study lead author and the Ralph C. Brown, MD, professor and chairman of Medicine, Rush University Medical Center, in a university press release.
Eleven percent of the U.S. population is affected by chronic kidney disease and progressive loss of kidney function, and the disease is seen as an increasing public health problem. Since patients with chronic kidney disease have a higher risk of developing cardiovascular disease, it is crucial to identify high-risk patients and begin to treat the causes leading to kidney injury.
Current methods for screening kidney disease are based on the measurement of urinary protein excretions and calculation of the estimated glomerular filtration rate (eGFR). However, these are considered bad markers for detecting early injury or a person’s disease risk. New, more sensitive biomarkers are thus required so that appropriate therapeutic interventions can be introduced early to halt disease progression.
In this study, authors performed a large, prospective cohort study to investigate if plasma suPAR levels were associated with new-onset chronic kidney disease. Elevated levels of suPAR were found both in circulation and membrane-bound forms in patients with several comorbidities and were associated with poor disease outcomes.
The team recruited a total of 3,683 patients with cardiovascular disease and measured how baseline levels of suPAR associated with kidney function, observing that in those with cardiovascular disease there was an association between elevated plasma suPAR levels and eGFR decline with development of chronic kidney disease. This association was found independently of standard risk factors for both kidney and cardiovascular diseases, including factors such as baseline eGFR, age, race, diabetes, and hypertension. Importantly, the team found that using suPAR levels in a prediction model significantly improved the assessment of patients’ future risk of chronic kidney disease, when compared to a standard clinical model (that does not include suPAR levels).
“We can now stratify people according to their risk of develop kidney disease using suPAR levels,” said Dr. Salim Hayek, study first author and fellow at the Emory Clinical Cardiovascular Research Institute.
“Today, nobody knows which patients with diabetes will get the disease. 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 will help risk-stratify specifically patients with diabetes on their risk of future kidney disease,” Dr. Reiser explained.
Dr. Sanja Sever from Massachusetts General Hospital and Harvard Medical School and study’s co-first author added, “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 gene polymorphism is 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.”