Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) and Impaired Kidney Function in the Population-based Malmö Diet and Cancer Study

INTRODUCTION: The soluble urokinase-type plasminogen activator receptor (suPAR) has recently been associated with a decline in kidney function and incidence of chronic kidney disease in patients with cardiovascular disease undergoing cardiac catheterization, yet little is known whether suPAR is associated with deterioration of kidney function in the general population. METHODS: In the population-based Malmö Diet and Cancer Study cohort, plasma levels of suPAR were quantified in 5381 participants at baseline (1991–1994), and creatinine was measured and used to calculate estimated glomerulus filtration rate (eGFR) at baseline and follow-up (2007–2012). Incident chronic kidney disease was defined as eGFR < 60 ml/min per 1.73 m(2) at follow-up. RESULTS: Participants within the highest quartile of suPAR had a significantly lower mean eGFR at follow-up than those within the lowest quartile (mean 68 vs. 74 ml/min per 1.73 m(2); P-trend = 4.3 × 10(–7)). In multivariate regression analysis, suPAR (per 1 SD increment of log-transformed suPAR) was associated with a decline in eGFR (P = 3.3 × 10(–9)) and incident chronic kidney disease (561 events, odds ratio = 1.25; 95% confidence interval, 1.10–1.41). Furthermore, we identified 110 cases of hospitalization due to impaired kidney function via linkage to national registers of inpatient and outpatient hospital diagnoses. During a mean follow-up time of 19 years, suPAR was associated with risk for hospitalization due to impaired kidney function (hazard ratio = 1.49; 95% confidence interval, 1.27–1.74) in multivariate Cox proportional hazard analysis. DISCUSSION: The increased suPAR level at baseline was associated with a significantly higher longitudinal decline in eGFR, higher incidence of chronic kidney disease, and hospitalization due to impaired kidney function in a cohort of healthy middle-aged participants.