Presepsin levels for discriminating sepsis and predicting mortality among organ failure patients stratified by hypercreatinemia

To evaluate the accuracy of presepsin levels in diagnosing sepsis and predicting mortality among organ failure patients with and without hypercreatinemia in the emergency department (ED). This retrospective study was conducted on patients with positive quick sequential organ failure assessment (qSOFA) score and increase in SOFA score of ≥2 points. Hypercreatinemia, indicated by a creatinine level of ≥1.2 mg/dL, was defined as points ≥1 on the renal component of the SOFA score. The patients were divided into group 1 (sepsis with hypercreatinemia), group 2 (sepsis without hypercreatinemia), group 3 (non-sepsis with hypercreatinemia), and group 4 (non-sepsis without hypercreatinemia), and their presepsin levels were compared. Receiver operating characteristic curve (ROC) analyses were performed to determine the accuracy of presepsin in diagnosing sepsis and predicting 30-day mortality. The optimal cutoff values were obtained to determine the presence of sepsis and predict the 30-day mortality. In all, 420 patients were eligible for this study. The presepsin levels in all pairwise comparisons between the groups were different (Group 1; 1311.5 (732.0–2179.5), Group 2; 566.5 (353.0–928.0), Group 3; 400.0 (291.0–579.0), Group 4; 231.0 (154.0–346.0)). Among patients with hypercreatinemia, the presepsin area under the ROC (AUROC) for diagnosing sepsis was 0.884 (optimal cutoff: 706 pg/mL). Among patients without hypercreatinemia, the presepsin AUROC for diagnosing sepsis was 0.854 (optimal cutoff: 352 pg/mL). The optimal cutoff values for predicting the patients’ 30-day mortality with and without hypercreatinemia were 1077 pg/mL and 393 pg/mL, respectively. Different cutoff values of presepsin based on creatinine levels could effectively diagnose sepsis in ED patients with organ failure. Further, presepsin was found to be associated with 30-day mortality in ED patients with organ failure, regardless of hypercreatinemia.

Kidney; Short-term mortality; Procalcitonin; Organ dysfunction scores

[1] Larsen FF, Petersen JA. Novel biomarkers for sepsis: a narrative review. European Journal of Internal Medicine. 2017; 45: 46–50.

[2] Kim H, Hur M, Moon HW, Yun YM, Di Somma S; GREAT Network. Multi-marker approach using procalcitonin, presepsin, galectin-3, and soluble suppression of tumorigenicity 2 for the prediction of mortality in sepsis. Annals of Intensive Care. 2017; 7: 27.

[3] Masson S, Caironi P, Fanizza C, Thomae R, Bernasconi R, Noto A, et al. Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock: data from the multicenter, randomized ALBIOS trial. Intensive Care Medicine. 2015; 41: 12–20.

[4] Endo S, Suzuki Y, Takahashi G, Shozushima T, Ishikura H, Murai A, et al. Usefulness of presepsin in the diagnosis of sepsis in a multicenter prospective study. Journal of Infection and Chemotherapy. 2012; 18: 891–897.

[5] Liu B, Chen Y, Yin Q, Zhao Y, Li C. Diagnostic value and prognostic evaluation of presepsin for sepsis in an emergency department. Critical Care. 2013; 17: R244.

[6] Masson S, Caironi P, Spanuth E, Thomae R, Panigada M, Sangiorgi G, et al. Presepsin (soluble CD14 subtype) and procalcitonin levels for mortality prediction in sepsis: data from the albumin italian outcome sepsis trial. Critical Care. 2014; 18: R6.

[7] Carpio R, Zapata J, Spanuth E, Hess G. Utility of presepsin (sCD14-ST) as a diagnostic and prognostic marker of sepsis in the emergency department. Clinica Chimica Acta. 2015; 450: 169–175.

[8] Chen M, Zhu Y. Utility of sTREM-1 and presepsin (sCD14-ST) as diagnostic and prognostic markers of sepsis. Clinical Laboratory. 2020; 66.

[9] Wu C, Lan H, Han S, Chaou C, Yeh C, Liu S, et al. Comparison of diagnostic accuracy in sepsis between presepsin, procalcitonin, and C- reactive protein: a systematic review and meta-analysis. Annals of Intensive Care. 2017; 7: 91.

[10] Kondo Y, Umemura Y, Hayashida K, Hara Y, Aihara M, Yamakawa K. Diagnostic value of procalcitonin and presepsin for sepsis in critically ill adult patients: a systematic review and meta-analysis. Journal of Intensive Care. 2019; 7: 22.

[11] Yang HS, Hur M, Yi A, Kim H, Lee S, Kim SN. Prognostic value of presepsin in adult patients with sepsis: Systematic review and meta-analysis. PLoS One. 2018; 13: e0191486.

[12] Imai Y, Taniguchi K, Iida R, Nitta M, Uchiyma K, Takasu A. Diagnostic accuracy of presepsin in predicting bacteraemia in elderly patients admitted to the emergency department: prospective study in Japan. BMJ Open. 2019; 9: e030421.

[13] Ulla M, Pizzolato E, Lucchiari M, Loiacono M, Soardo F, Forno D, et al. Diagnostic and prognostic value of presepsin in the management of sepsis in the emergency department: a multicenter prospective study. Critical Care. 2013; 17: R168.

[14] Ruangsomboon O, Panjaikaew P, Monsomboon A, Chakorn T, Permpikul C, Limsuwat C. Diagnostic and prognostic utility of presepsin for sepsis in very elderly patients in the emergency department. Clinica Chimica Acta. 2020; 510: 723–732.

[15] Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016; 315: 801.

[16] Contenti J, Occelli C, Lemoel F, Ferrari P, Levraut J. Presepsin versus other biomarkers to predict sepsis and septic shock in patients with infection defined by Sepsis-3 criteria: the PREDI study of diagnostic accuracy. Emergencias. 2019; 31: 311–317.

[17] Yamamoto T, Nishimura T, Kaga S, Uchida K, Tachibana Y, Esaki M, et al. Diagnostic accuracy of presepsin for sepsis by the new Sepsis-3 definitions. The American Journal of Emergency Medicine. 2019; 37: 1936–1941.

[18] Aliu-Bejta A, Atelj A, Kurshumliu M, Dreshaj S, Baršić B. Presepsin values as markers of severity of sepsis. International Journal of Infectious Diseases. 2020; 95: 1–7.

[19] Lu B, Zhang Y, Li C, Liu C, Yao Y, Su M, et al. The utility of presepsin in diagnosis and risk stratification for the emergency patients with sepsis. The American Journal of Emergency Medicine. 2018; 36: 1341–1345.

[20] Chenevier-Gobeaux C, Trabattoni E, Roelens M, Borderie D, Claessens Y. Presepsin (sCD14-ST) in emergency department: the need for adapted threshold values? Clinica Chimica Acta. 2014; 427: 34–36.

[21] Behnes M, Bertsch T, Lepiorz D, Lang S, Trinkmann F, Brueckmann M, et al. Diagnostic and prognostic utility of soluble CD 14 subtype (presepsin) for severe sepsis and septic shock during the first week of intensive care treatment. Critical Care. 2014; 18: 507.

[22] Nagata T, Yasuda Y, Ando M, Abe T, Katsuno T, Kato S, et al. Clinical impact of kidney function on presepsin levels. PLoS One. 2015; 10: e0129159.

[23] Miyoshi M, Inoue Y, Nishioka M, Ikegame A, Nakao T, Kishi S, et al. Clinical evaluation of presepsin considering renal function. PLoS One. 2019; 14: e0215791.

[24] Shimoyama Y, Umegaki O, Kadono N, Minami T. Presepsin values predict septic acute kidney injury, acute respiratory distress syndrome, disseminated intravascular coagulation, and shock. Shock. 2021; 55: 501–506.

[25] Smith GB, Prytherch DR, Meredith P, Schmidt PE, Featherstone PI. The ability of the national early warning score (NEWS) to discriminate patients at risk of early cardiac arrest, unanticipated intensive care unit admission, and death. Resuscitation. 2013; 84: 465–470.

[26] Scott LJ, Redmond NM, Tavaré A, Little H, Srivastava S, Pullyblank A. Association between national early warning scores in primary care and clinical outcomes: an observational study in UK primary and secondary care. British Journal of General Practice. 2020; 70: e374–e380.

[27] Subbe CP. Validation of a modified early warning score in medical admissions. QJM. 2001; 94: 521–526.

[28] Nakamura Y, Ishikura H, Nishida T, Kawano Y, Yuge R, Ichiki R, et al. Usefulness of presepsin in the diagnosis of sepsis in patients with or without acute kidney injury. BMC Anesthesiology. 2014; 14: 88.

[29] Nakamura Y, Hoshino K, Kiyomi F, Kawano Y, Mizunuma M, Tanaka J, et al. Comparison of accuracy of presepsin and procalcitonin concentrations in diagnosing sepsis in patients with and without acute kidney injury. Clinica Chimica Acta. 2019; 490: 200–206.

[30] Alice ND, Vlad P, Andrea DS, Luminita CC, Dan NF, Ioana AG, et al. Presepsin as a potential prognostic marker for sepsis according to actual practice guidelines. Journal of Personalized Medicine. 2020; 11: 2.

[31] Laura E, Andrew R, Waleed A, Massimo A, Craig MC, Craig F, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Medicine. 2021; 47: 1181–1247.

[32] Ali FT, Ali MAM, Elnakeeb MM, Bendary HNM. Presepsin is an early monitoring biomarker for predicting clinical outcome in patients with sepsis. Clinica Chimica Acta. 2016; 460: 93–101.

[33] Wen MY, Huang LQ, Yang F, Ye JK, Cai GX, Li XS, et al. Presepsin level in predicting patients’ in-hospital mortality from sepsis under sepsis-3 criteria. Therapeutics and Clinical Risk Management. 2019; 15: 733–739.