Sensitivity and specificity of procalcitonin in predicting bacterial infections in patients with renal impairment.

The measurement of serum concentrations of procalcitonin is a comparatively new and important laboratory tool for predicting the presence of a bacterial infection in patients presenting with sepsis. It has been proposed that the use of procalcitonin can reduce inappropriate antibiotic exposure by ruling out bacterial infection more reliably and accurately than previously used measures including C-reactive protein or white blood cell count [1–4]. Conflicting reports suggest that antibiotics might be used more frequently as a consequence of discovering elevated serum procalcitonin levels in patients, with other data demonstrating no increase in survival, prolonged admission, harm related to antibiotic side effects, and increasing antibiotic resistance [5]. Procalcitonin levels are increased in inflammatory conditions in the absence of bacterial infection, such as acute pancreatitis [6]. These findings are relevant to patients with renal impairment, which is regarded as a proinflammatory state [7]. Therefore renal impairment may affect serum procalcitonin levels, irrespective of the presence or absence of bacterial infection [8–10]. Several studies have evaluated the specificity and sensitivity of procalcitonin in the general population, without regard for estimated glomerular filtration rate (eGFR) [11–14]. One study by Herget-Rosenthal et al [15] demonstrated an increase in procalcitonin levels in correlation to chronic kidney disease stage, peritoneal dialysis, cardiovascular disease, and oliguria. A recent meta-analysis by Lu et al [16], which reviews 7 diagnostic studies and evaluates 803 patients, demonstrates a hierarchical summary receiver operating characteristic-bivariate pooled sensitivity estimate of 73%; however, the applicability of these results remain in question secondary to the wide diversity of the populations evaluated in the various studies. Schuetz et al [1] reported that the mean procalcitonin level in uninfected patients undergoing hemodialysis was 0.49 ± 0.36 ng/mL, compared with 0.12 ± 0.06 ng/mL in uninfected patients with mild to advanced chronic renal failure. One theory to explain this finding is that the elevated procalcitonin level may be related to the crossing of endotoxins or endotoxin fragments across high- and low-flux dialysis membranes, leading to activation of monocytes and production of proinflammatory cytokines, which in turn may stimulate the release of procalcitonin [17–19]. This same study claimed a 97% sensitivity and specificity of procalcitonin levels to predict bacterial infection in 35 patients with chronic renal failure, end-stage renal disease, renal transplants patients, and those with varying comorbidities, using a cutoff of 1.5 ng/mL; however, there are many logistical and statistical questions regarding the generalized application of this result [1]. We investigated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), best predictive value, and accuracy of procalcitonin in detecting bacterial infections in patients with renal impairment, specifically in those with modification in diet in renal disease (MDRD) eGFR ≤30 mL/min per 1.73 m2 during their hospital stay [20]. We performed separate subgroup analysis on patients with bacteremia vs those without any infection and attempted to correlate procalcitonin levels to eGFR and in an attempt to improve the sensitivity and specificity of procalcitonin in patients with renal insufficiency.