Soluble Urokinase Receptor and Chronic Kidney Disease, 2015
Chronic kidney disease and progressive loss of kidney function constitute a major public health problem affecting 11% of the U.S. population.1 Patients with chronic kidney disease are at high risk for cardiovascular disease and death.2 It is thus important to identify patients at high risk for chronic kidney disease and to treat underlying disease processes that drive kidney injury.3 In clinical practice, methods of screening for kidney disease are limited to measurement of urinary protein excretion and calculation of the estimated glomerular filtration rate (eGFR). Proteinuria and a decline in the eGFR are relatively insensitive indexes of early injury and have limited usefulness in mass screening for chronic kidney disease.3-5 Hence, more sensitive biomarkers are required to identify at-risk patients earlier in the disease process in order to develop and study interventions aimed at preventing the progression to chronic kidney disease.
Soluble urokinase-type plasminogen activator receptor (suPAR) is the circulating form of a glycosyl-phosphatidylinositol–anchored three-domain membrane protein that is expressed on a variety of cells, including immunologically active cells, endothelial cells, and podocytes.6-8 Both the circulating and membrane-bound forms are directly involved in the regulation of cell adhesion and migration through binding of integrins.6 The circulating form is produced by cleavage of membrane-bound urokinase-type plasminogen activator receptor and is readily detected in plasma, serum, urine, and other bodily fluids.9-11 Elevated suPAR levels have been associated with poor outcomes in various patient populations.12-20 In addition, suPAR has been implicated in the pathogenesis of kidney disease, specifically focal segmental glomerulosclerosis and diabetic nephropathy, through interference with podocyte migration and apoptosis.7,13,21,22 Although these findings are still under investigation,23 they suggest a possible broader role of suPAR in kidney disease. Therefore, in a large, prospective cohort study involving patients with cardiovascular disease, we tested the hypothesis that plasma suPAR levels are associated with new-onset chronic kidney disease.