Screening for kidney disease is limited in that we rely on measuring urinary protein excretion and calculating estimated glomerular filtration rates (eGFRs). Unfortunately, proteinuria and decline in estimated glomerular filtration rates (eGFRs) are relatively insensitive identifiers of early injury and chronic kidney disease (CKD). Recent studies suggest that elevated levels of soluble urokinase-type plasminogen activator receptor (suPAR) are associated with poor outcomes in various patient populations. In addition, suPAR has been implicated in the pathogenesis of kidney disease. It is thought that suPAR interferes with podocyte motility and viability. “Given the growing role for podocytes in the development of CKD, these findings indicate that there may be a more general role for suPAR in kidney disease,” says Dr. Reiser.
In a study involving patients with risk for cardiovascular disease (CVD) published in New England Journal of Medicine, Dr. Reiser and colleagues tested the hypothesis that plasma suPAR levels are associated with new-onset CKD. Plasma suPAR levels were measured in more than 3,600 patients. The study group determined renal function at enrollment and at subsequent visits in 2,292 participants and examined the relationship between suPAR levels and eGFR at baseline, changes in eGFR, and the development of CKD.
“Elevated suPAR levels were associated with incident CKD and a more rapid decline in the eGFR in people who had normal kidney function at baseline,” says Dr. Reiser. The 921 participants with a normal eGFR (≥90 ml per minute per 1.73 m2) at baseline had the largest suPAR-related decline in the eGFR. In 1,335 participants with a baseline eGFR of at least 60 ml per minute per 1.73 m2, the risk of progression to CKD in the highest quartile of suPAR levels was 3.13 times as high as that seen in the lowest quartile. “Our findings were corrected for and found to be independent of conventional risk factors for kidney disease and CVD,” adds Dr. Reiser.
The study also showed that including suPAR levels in a prediction model significantly improved discrimination of future risk of CKD when compared with using a standard clinical model, according to Dr. Reiser. “We found that suPAR was associated with a decline in renal function among younger people, a patient group that had a significantly lower burden of risk factors for CVD,” he says. “This suggests that the effect of suPAR is truly independent of traditional risk factors for CVD and CKD.”