Presepsin Cut-Offs for Sepsis Risk Stratification
Presepsin levels <300 pg/mL indicate low risk, 300–600 pg/mL intermediate risk, and >600 pg/mL high risk for sepsis in adults with suspected bacterial infection; however, these thresholds must be interpreted with extreme caution in chronic kidney disease patients, where presepsin accumulates due to impaired renal clearance, and current evidence does not provide validated pediatric cut-offs.
Diagnostic Thresholds in Adults with Normal Renal Function
Risk Stratification by Presepsin Level
Low risk (<300 pg/mL): Presepsin values in healthy individuals average 294.2 ± 121.4 pg/mL, establishing this as the upper limit of normal and indicating low probability of sepsis. 1
Intermediate risk (300–600 pg/mL): Patients with local infection (not systemic sepsis) demonstrate presepsin levels of 721.0 ± 611.3 pg/mL, suggesting this range represents possible infection without systemic involvement. 1
High risk (>600 pg/mL): Sepsis patients show presepsin values of 817.9 ± 572.7 pg/mL, while severe sepsis elevates levels to 1,992.9 ± 1,509.2 pg/mL, establishing >600 pg/mL as the threshold for probable sepsis. 1
Comparative Diagnostic Performance
Presepsin demonstrates superior diagnostic accuracy compared to conventional biomarkers, with an area under the ROC curve of 0.845 for sepsis diagnosis—significantly higher than procalcitonin (0.652), C-reactive protein (0.815), or interleukin-6 (0.672). 1
For predicting bacteremia specifically, presepsin achieves an AUC of 0.788 (95% CI: 0.687–0.889), with median values of 1,290 pg/mL in bacteremic patients versus 659 pg/mL in non-bacteremic patients (P<0.001). 2
Presepsin performs comparably to procalcitonin for bacteremia prediction (PCT AUC 0.876, P=0.12 for difference) but both significantly outperform CRP (AUC 0.602). 2
Critical Adjustments for Chronic Kidney Disease
Renal Clearance and Accumulation
Presepsin is a 13 kDa molecule that undergoes complete glomerular filtration and proximal tubular reabsorption/metabolism, making plasma levels highly dependent on renal function. 3
Both acute kidney injury during sepsis and pre-existing chronic kidney disease significantly elevate presepsin levels independent of infection severity, confounding interpretation. 3
Practical Approach in CKD Patients
No validated cut-offs exist for CKD populations—presepsin should be used only for serial monitoring (tracking trends over time) rather than single-point diagnosis in patients with renal impairment. 3
Procalcitonin remains the preferred biomarker in CKD patients because it is markedly influenced by renal function and renal replacement therapy but has more established correction factors. 4
In dialysis-dependent patients, obtain presepsin measurements at consistent time points relative to dialysis sessions (e.g., pre-dialysis only) to minimize variability, though this approach lacks formal validation. 3
Pediatric Considerations
Evidence Gap
Current presepsin literature derives almost entirely from adult populations, with no established pediatric reference ranges or sepsis cut-offs. The studies reviewed 2, 1, 5, 6, 3 do not include pediatric cohorts.
Procalcitonin has better-established pediatric thresholds (0.5 ng/mL for low risk, 2.0 ng/mL for sepsis, >10 ng/mL for septic shock) and should be prioritized in children until pediatric presepsin data emerge. 4, 7
Clinical Integration Algorithm
When to Measure Presepsin
Measure presepsin only when the pre-test probability of bacterial infection is low-to-intermediate (new fever without clear source), as an adjunct to clinical assessment—never as a standalone test. 8, 4
Do not measure presepsin when clinical suspicion for sepsis is high—initiate empiric broad-spectrum antibiotics within 1 hour regardless of biomarker results. 8, 4
Obtain baseline presepsin before antibiotics (if no delay >45 minutes) to establish a reference for serial monitoring. 4, 7
Interpretation Framework
| Presepsin Level | Clinical Interpretation | Recommended Action |
|---|---|---|
| <300 pg/mL | Low probability of sepsis | Consider withholding antibiotics if clinically stable [1] |
| 300–600 pg/mL | Indeterminate; possible localized infection | Correlate with clinical findings, imaging, cultures [1] |
| 600–1,000 pg/mL | Probable sepsis | Initiate antibiotics based on overall assessment [1,6] |
| >1,000 pg/mL | High probability of bacteremia/sepsis | Immediate empiric antibiotics and source control [2,1] |
| >2,000 pg/mL | Severe sepsis/septic shock | Aggressive resuscitation per Surviving Sepsis guidelines [1] |
Serial Monitoring for Treatment Response
Presepsin decreases significantly during effective antibiotic therapy—falling levels from day 1 to day 7 predict favorable outcomes and support antibiotic de-escalation. 5
Rising presepsin from day 1 to day 2 independently predicts ICU and 90-day mortality (adjusted P<0.0001 and 0.01, respectively), indicating treatment failure or secondary infection. 5
Presepsin concentration increases with inappropriate antibiotic therapy (P=0.0009), making serial measurements valuable for assessing therapeutic adequacy. 5
Common Pitfalls and Caveats
Timing of Sampling
Early sampling (<6 hours after symptom onset) may yield falsely low presepsin results because the biomarker requires time to accumulate—optimal sampling occurs ≥6 hours after presentation. 4
Presepsin kinetics are faster than CRP (which peaks at 36–50 hours) but comparable to procalcitonin (which rises at 2–3 hours and peaks at 6–8 hours). 4, 7
False Elevations
Presepsin cannot reliably distinguish bacterial sepsis from severe viral illness—approximately 21% of COVID-19 patients without bacterial co-infection show elevated presepsin due to hyperinflammatory states. 4, 9
Non-infectious causes of presepsin elevation include acute respiratory distress syndrome, chemical pneumonitis, and severe falciparum malaria. 9
Renal Dysfunction
The single greatest limitation of presepsin is its dependence on renal clearance—any degree of kidney impairment (acute or chronic) invalidates standard cut-offs. 3
In patients with estimated GFR <60 mL/min/1.73m², consider procalcitonin (with its own renal caveats) or rely on clinical assessment and culture data rather than presepsin thresholds. 4, 3
Guideline Positioning
Major sepsis guidelines (Surviving Sepsis Campaign, Society of Critical Care Medicine) do not currently recommend presepsin because evidence remains insufficient compared to procalcitonin, which has weak recommendations (Grade 2C) for guiding antibiotic discontinuation. 8, 4
Presepsin should be viewed as an investigational adjunct rather than a standard-of-care biomarker until incorporated into formal guidelines. 8, 4