Soluble urokinase plasminogen activator receptor and decline in kidney function among patients without kidney disease

Abstract

Background: Hospitalized patients are at an increased risk of developing kidney disease after discharge, often despite the absence of any clinical indicators during hospitalization. Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic chronic inflammation that can be measured from routine blood samples. We determined whether elevated suPAR during hospitalization is associated with a decline in estimated glomerular filtration rate (eGFR) after discharge.

Methods: This was a retrospective longitudinal cohort study of patients without detectable kidney disease presenting to the emergency department on two separate occasions during a 3-year period. The association between suPAR and a decline in eGFR was assessed by linear mixed models for repeated measures adjusting for age, sex, C-reactive protein, sodium, diabetes, hypertension and cardiovascular disease.

Results: In total, 5124 patients (median age 65.9 years, 51.0% female) were included. The median suPAR was 2.9 ng/mL, the median time to readmission was 144 days and the expected rate of eGFR decline over this period was 5.1 mL/min/1.73 m²/year. Adjusting for other risk factors, patients with suPAR <3, 3-6 or ≥6 ng/mL had an expected eGFR decline of 4.3, 5.2 or 9.0 mL/min/1.73 m²/year, respectively. Similarly, patients with suPAR in the lowest (<2.4 ng/mL), middle (2.4-3.6 ng/mL) or highest (≥3.6 ng/mL) tertile had an expected eGFR decline of 4.2, 4.6 or 6.5 mL/min/1.73 m²/year, respectively. In both cases, a higher suPAR level was significantly and independently associated with a higher rate of eGFR decline (P < .001).

Conclusions: A higher suPAR level was associated with accelerated eGFR decline among patients presenting to the emergency department, suggesting that routine suPAR measurements may have utility for the early detection of kidney disease.

Keywords: acute; emergency department; estimated glomerular filtration rate; kidney disease; soluble urokinase plasminogen activator receptor.

Graphical Abstract

FIGURE 1:

Change in eGFR according to suPAR level. Non-parametric quantile regression of change in eGFR over time according to suPAR level at index admission.

FIGURE 2:

Impact of age and sex on suPAR-related eGFR decline. Graphical representation of combined model estimates for age, sex and suPAR level.