Diagnostic performance of procalcitonin for differentiating infectious and non-infectious conditions in emergency department patients with reduced kidney function

Early differentiation of infectious and non-infectious conditions in emergency department (ED) patients is challenging, particularly in patients with reduced kidney function. Procalcitonin (PCT) has been proposed as a useful biomarker for bacterial infections; however, its diagnostic performance may be influenced by renal function. To evaluate the diagnostic accuracy of procalcitonin for distinguishing infectious from non-infectious conditions in emergency department patients with reduced kidney function, and to examine whether its discriminative performance and optimal threshold differ across levels of kidney function. Prospective cross-sectional diagnostic accuracy study in the emergency department of a tertiary hospital. Consecutive adults with an admission estimated glomerular filtration rate (eGFR) below 90 mL/min/1.73 m² in whom the treating clinician requested procalcitonin were enrolled. Infection was adjudicated by two emergency physicians using clinical findings, routine inflammatory markers and imaging or urinalysis; procalcitonin did not contribute to this reference standard. Patients were stratified by admission eGFR into those below 15 and those between 15 and 90 mL/min/1.73 m², calculated with the CKD-EPI 2009 equation. Areas under the receiver operating characteristic curve were compared between strata with a test for two independent areas, and all analyses were repeated using a reference standard based on imaging and urinalysis alone. Of 478 patients, 162 (33.9%) were classified as infected. Procalcitonin discriminated infection with an area under the curve of 0.753 (95% CI 0.704 to 0.802); at the Youden-optimal threshold of 0.34 ng/mL, sensitivity was 54.9% and specificity 87.3%. In the 74 patients with an eGFR below 15 mL/min/1.73 m² the area under the curve was 0.861 (0.763 to 0.960) and the optimal threshold 0.56 ng/mL; in the 404 patients with an eGFR of 15 to 90 mL/min/1.73 m² it was 0.751 (0.697 to 0.805) with an optimal threshold of 0.23 ng/mL. The difference between strata was 0.110 (95% CI − 0.002 to 0.222; p = 0.053). C-reactive protein discriminated at least as well as procalcitonin (0.815 versus 0.753, p = 0.002). When infection was redefined without any contribution from blood-based markers, procalcitonin performance was unchanged (0.755), the difference between strata disappeared ( p = 0.615), and the difference in optimal thresholds persisted. Procalcitonin identified infection with moderate accuracy in emergency department patients with reduced kidney function, and its discriminative performance did not differ significantly by kidney function stratum. The concentration at which it became informative did differ, being more than twice as high in kidney failure as at better preserved levels of function. Applying a single population-derived threshold across the range of kidney function is therefore likely to misclassify patients with kidney failure. These exploratory thresholds require confirmation in independent cohorts.