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Modified Yeast-Two-Hybrid System to Identify Proteins Interacting with the Growth Factor Progranulin
Published on: January 17, 2012
Progranulin Is a Useful Biomarker to Predict Mortality in ICU Patients with Low Burden of Organ Dysfunction
Jochen Johannes Schoettler1, Lutz Pridzun2, Bertram Flehmig2
1Department of Anesthesiology, Surgical Intensive Care Medicine and Pain Medicine, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Insights
Progranulin (PGRN) levels can predict in-hospital mortality in intensive care unit (ICU) patients with low burden of organ dysfunction (BOD). Serial PGRN measurements offer prognostic value where traditional scores like SOFA may underestimate risk.
Area of Science:
- Critical Care Medicine
- Biomarkers
- Prognostic Medicine
Background:
- Early prognostication for critically ill patients with low burden of organ dysfunction (BOD) is challenging.
- Progranulin (PGRN), a hypoxia-inducible and anti-inflammatory protein, may hold prognostic significance.
- Investigating PGRN's role in predicting mortality in ICU patients stratified by BOD.
Purpose of the Study:
- To determine if plasma Progranulin (PGRN) levels predict in-hospital mortality in intensive care unit (ICU) patients.
- To stratify patients based on burden of organ dysfunction (BOD) using Sequential Organ Failure Assessment (SOFA) scores.
- To evaluate the prognostic value of initial PGRN concentrations and kinetic parameters.
Main Methods:
- Secondary analysis of a prospectively recruited ICU cohort (n=99).
- Patients categorized into low (SOFA ≤ 8) and high (SOFA > 8) BOD groups.
- Plasma PGRN measured every 8 h for up to 5 days; initial values and kinetics (max, mean, NAS) analyzed against in-hospital mortality using logistic regression and AUROC.
Main Results:
- In low BOD patients (n=53), PGRN kinetics (max, mean, NAS) significantly predicted mortality (AUROC 0.738-0.815, p≤0.016).
- No PGRN metrics predicted mortality in high BOD patients (n=46; AUROC < 0.61, p>0.25).
- Maximum PGRN levels predicted death at least 32 hours in advance; SOFA and CRP were not predictive in low BOD patients.
Conclusions:
- Serial Progranulin (PGRN) measurements provide prognostic information, especially in ICU patients with low burden of organ dysfunction (BOD).
- PGRN offers value in identifying patients at risk of deterioration where conventional scores like SOFA may be insufficient.
- Findings support further research into PGRN for early risk stratification in critical illness.
Abstract:
Background/Objectives: Early prognostication in critically ill patients with low burden of organ dysfunction (BOD) remains challenging. Progranulin (PGRN), a hypoxia inducible and anti-inflammatory protein, may offer prognostic value. We investigated whether PGRN levels predict mortality in ICU patients stratified by their BOD. Methods: In this secondary analysis of a prospectively recruited ICU cohort (n = 99), patients were categorized into low (Sequential Organ Failure Assessment Score (SOFA) ≤ 8) and high (SOFA > 8) BOD groups. Plasma PGRN concentrations were measured every 8 h for up to 5 days. Initial values and kinetic parameters (maximum, mean, and normalized area score (NAS)) were evaluated. Associations with in-hospital mortality were analyzed by univariate logistic regression and area under the receiver operating characteristic curve (AUROC) comparisons. Results: In patients with low BOD (n = 53), the PGRN kinetics were significantly associated with in-hospital mortality, with odds ratios of 1.086 (95% CI 1.027-1.148), 1.102 (95% CI 1.025-1.184), and 1.093 (95% CI 1.021-1.170) for maximum, mean, and NAS values, respectively. The respective AUROC values were 0.815 (p = 0.001), 0.753 (p = 0.010), and 0.738 (p = 0.016). By contrast, none of the PGRN metrics predicted mortality in patients with high BOD (n = 46; all AUROC values < 0.61, p > 0.25). The respective SOFA and CRP metrics were not predictive in low BOD patients. Maximum PGRN levels predicted death at least 32 h in advance. Conclusions: Serial PGRN measurements offer prognostic information, particularly in ICU patients with low BOD, a group whose deterioration is often difficult to anticipate and may be underestimated by conventional scoring systems such as SOFA. These findings support further investigation of PGRN as a tool for early risk stratification in critical illness.
