Does procalcitonin (PCT) falsely elevate in patients with Chronic Kidney Disease (CKD)?

Does Procalcitonin Rise Falsely High in CKD?

Yes, procalcitonin (PCT) levels are frequently elevated in patients with chronic kidney disease (CKD) even in the absence of bacterial infection, making interpretation challenging but not impossible when proper thresholds and clinical context are applied.

Understanding PCT Elevation in CKD

PCT levels progressively increase as kidney function declines, with the elevation occurring through two distinct mechanisms 1:

• Reduced renal clearance: As glomerular filtration rate (GFR) decreases, PCT accumulation occurs due to impaired elimination 1
• Increased synthesis: Peripheral blood mononuclear cells (PBMC) in CKD patients produce significantly more PCT than in healthy individuals, with PBMC PCT release correlating closely with serum PCT levels (r=0.76) 1

In the absence of infection, 92% of plasma PCT measurements in critically ill patients with either acute kidney injury (AKI) or end-stage kidney disease (ESKD) were ≥0.5 ng/mL—well above the traditional diagnostic threshold for bacterial infection 2.

Baseline PCT Levels by CKD Stage

PCT elevation correlates with severity of kidney disease 3, 1:

• Healthy controls: Median 0.03 ng/mL 3
• CKD not on dialysis: Median 0.12 ng/mL 3
• Peritoneal dialysis: Median 0.32 ng/mL 3
• Hemodialysis: Median 0.79 ng/mL 3

Additional factors independently associated with PCT elevation include oliguria, cardiovascular disease, and elevated C-reactive protein 1.

Diagnostic Accuracy in CKD Populations

Despite baseline elevation, PCT can still distinguish infected from non-infected patients when appropriate thresholds are used:

For Dialysis and CKD Patients with Confirmed Infections

Patients with confirmed systemic bacterial infections had significantly higher PCT values (median 2.5 ng/mL, interquartile range 0.9-5 ng/mL) compared to those without infection (median 0.3 ng/mL, interquartile range 0.1-0.5 ng/mL) 4.

Using a cutoff of 0.5 ng/mL in CKD patients yielded sensitivity of 93.1% and specificity of 78.6% for systemic bacterial infection 4.

Optimal Thresholds Vary by Type of Renal Dysfunction

A 2020 study determined type-specific optimal PCT thresholds 5:

• Acute kidney injury (AKI): 1.5 ng/mL 5
• Chronic kidney disease (CKD): 0.1 ng/mL 5
• End-stage renal disease (ESRD): 1.75 ng/mL 5

These differ substantially from traditional thresholds (0.5 ng/mL for sepsis, 0.25 ng/mL for pneumonia) 5.

Critical Limitations in Critically Ill Patients with Kidney Failure

In critically ill patients requiring continuous kidney replacement therapy (CKRT), PCT cannot reliably distinguish septic from non-septic status 2:

• Pre-CKRT median PCT in non-septic AKI: 5.6 ng/mL 2
• Pre-CKRT median PCT in septic AKI: 58.1 ng/mL (P=0.03, but substantial overlap) 2
• Pre-CKRT median PCT in non-septic ESKD: 3.3 ng/mL 2
• Pre-CKRT median PCT in septic ESKD: 3.7 ng/mL (P=0.79, no significant difference) 2

ROC curve analysis found no cutpoint that could reliably separate septic from non-septic critically ill patients with kidney failure 2.

Effect of Dialysis on PCT Levels

During Hemodialysis

• PCT sieving coefficient during continuous venovenous hemodialysis is approximately 0.2, meaning effluent PCT levels are consistently ~20% of plasma levels 2
• Despite clearance during therapy, plasma PCT levels do not significantly decline during CKRT in either AKI or ESKD 2
• Standard hemodialysis generally increases troponin T but decreases troponin I (for comparison with another cardiac biomarker affected by dialysis) 6

Timing of Blood Sampling

Blood samples for PCT should be drawn before dialysis in hemodialysis patients, as dialysis can affect biomarker levels 6, 7.

Clinical Approach to PCT Interpretation in CKD

When PCT Remains Useful

PCT maintains diagnostic value in stable CKD patients (not critically ill) when using adjusted thresholds specific to the type and severity of renal dysfunction 5, 4.

For patients with CKD stages 3-4 and dialysis patients with strong clinical suspicion of systemic bacterial infection, significantly elevated PCT concentrations offer good sensitivity (93.1%) and acceptable specificity (78.6%) 4.

When to Avoid PCT Testing

PCT testing should be avoided in critically ill patients with kidney failure requiring CKRT, as results are nonspecific in this population and cannot distinguish septic from non-septic status 2.

The guideline on fever evaluation in critically ill patients notes that PCT can be employed as an adjunctive diagnostic tool for discriminating infection, but chronic inflammatory states are not associated with PCT increment 6. However, this guidance predates the 2025 evidence showing marked PCT elevation in non-septic kidney failure 2.

Alternative Diagnostic Strategies

Serial PCT Measurements

Rather than relying on a single elevated value, assess for dynamic changes over time 8:

• PCT typically rises within 2-3 hours of bacterial infection onset 6, 8
• Serial measurements showing rising trends suggest active infection 8
• A PCT ratio (day 1 to day 2) >1.14 following surgical procedures suggests unsuccessful source control 8

Complementary Biomarkers

Consider using PCT in conjunction with other markers 6:

• Ferritin-to-procalcitonin ratio ≥877 has 85% sensitivity and 56% specificity for differentiating COVID-19 from bacterial pneumonia 6
• Baseline white blood cell count and change in C-reactive protein within 48 hours of antibiotics can help exclude bacterial co-infection in 46% of cases 6

Clinical Context Remains Paramount

Do not delay empiric antibiotic therapy in critically ill CKD patients while awaiting PCT results if bacterial infection is clinically suspected 6, 8. PCT should never be used in isolation but rather integrated with clinical presentation, imaging, and microbiologic data 6.

Key Pitfalls to Avoid

• Do not apply standard PCT thresholds (0.25-0.5 ng/mL) to CKD patients—these will result in false positives 5, 2
• Do not use PCT as the sole determinant for antibiotic decisions in ESKD or critically ill AKI patients—the overlap between infected and non-infected patients is too substantial 2
• Do not assume elevated PCT in CKD always indicates infection—it may reflect chronic inflammation, cardiovascular disease, or reduced clearance 1
• Do not draw PCT samples after hemodialysis—obtain them pre-dialysis for more accurate interpretation 6, 7