New diagnostic tool for the management of patients with sepsis: Dipeptidyl Peptidase 3 (DPP3)
- DPP3 has been shown to be a cardiac depression factor and a marker for refractory shock
- DPP3 outperforms Lactate and Procalcitonin on the short-term prognosis in sepsis
- Changes in the DPP3 levels indicate the worsening or improving of the patient’s condition
- DPP3 markedly guides intensivists in the management of septic patients
Hennigsdorf/Berlin, Germany, March 23, 2021 –
Diagnostics company SphingoTec GmbH (“SphingoTec”) announced today the first published data (1) on the biomarker DPP3 that can predict the evolution of organ function and survival in septic patients. Measured on top of routinely used standard parameters, such as Lactate and Procalcitonin, DPP3 is an early indicator of short-term outcomes and patient severity. Sepsis is a medical emergency caused by a dysregulated host response to an infection, with mortality rates increasing rapidly for each hour that appropriate treatment is delayed (2). The rapid evolution of sepsis into its severe form, septic shock, raises the need for more precise and faster testing to support better clinical decision-making.
DPP3 is an enzyme at the core of a newly discovered disease mechanism responsible for cardiovascular depression and short-term organ failure in critically ill patients. Although intracellular DPP3 is involved in normal metabolic processes (3), massive cell death leads to DPP3 release into the bloodstream. Circulating DPP3 inactivates Angiotensin II, a hormone regulating the renin-angiotensin-aldosterone system (RAAS), which ultimately controls hemodynamics (4,5). Angiotensin II depletion leads to cardiovascular depression (6,7,9,10) and reduced vascular tone (6,8), a hemodynamic instability that quickly escalates in multiple organ failure. DPP3 was already shown to add value in various critical care settings such as cardiogenic shock (7,9) and burn shock (10).
The data from the prospective observational multi-center AdrenoOSS-1 study enrolling about 600 patients with sepsis and septic shock have shown that DPP3 levels can predict multiple short-term organ failure and the need for organ support therapies in this population (1). High or increasing DPP3 blood levels precede organ injury and predict the need for vasopressor/inotropic use, mechanical ventilation, and renal replacement therapy. DPP3 blood levels also reflect patient severity, with septic shock patients having a significantly higher DPP3 concentration than patients with severe sepsis (1,3). The study data further show that low or decreasing levels of DPP3 in the first 24 hours of ICU admission predict an improvement of organ function and better outcomes. The dynamic nature of the biomarker can guide intensivists in the early management of septic shock patients.
Dr. Andreas Bergmann, founder of various companies, where new tools to fight sepsis mortality are developed, and CEO of critical care diagnostics company SphingoTec commented: “This newly discovered biomarker makes it easy to identify a distinct pathophysiological mechanism leading to mortality in sepsis and uncovers the etiology of clinical symptoms. The published data show that measuring DPP3 levels add value in the clinical practice by early revealing organ injury and adding information on top of standard parameters. This can help guide intensivists in the early management of septic patients.“
The in vitro diagnostic test for DPP3 is available as a microtiter plate as well as a near-patient rapid test (IB10 sphingotest® DPP3). SphingoTec has made the test available for the critical care community to further assess the clinical utility of the DPP3 biomarker in acute care settings.
References
1. Blet et al (2021), Monitoring Circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study, Crit Care, DOI: https://doi.org/10.1186/s13054-021-03471-2
2. Bai et al (2014) Early versus delayed administration of norepinephrine in patients with septic shock Crit Care..DOI:https://doi.org/10.1186/s13054-014-0532-y
3. Rehfeld et al (2019). Novel Methods for the Quantification of Dipeptidyl Peptidase 3 (DPP3) Concentration and Activity in Human Blood Samples. J Appl Lab Med. DOI: 10.1373/jalm.2018.027995
4. Picod et al (2020), Alteration of the Renin-Angiotensin-Aldosterone System in Shock: Role of the Dipeptidyl Peptidase 3, Am J Respir Crit Care Med, 2020, DOI: 10.1164/rccm.202010-3873LE
5. Jha et al (2020), Dipeptidyl peptidase 3 modulates the renin–angiotensin system in mice, J Biol Chem., DOI: 10.1074/jbc.RA120.014183.
6. Deniau et al.(2020) Inhibition of circulating dipeptidyl-peptidase 3 restores cardiac function in a sepsis-induced model in rats: A proof of concept study. PloS One. DOI: doi.org/10.1371/journal.pone.0238039
7. Takagi et al.(2019) Circulating dipeptidyl peptidase 3 and alteration in haemodynamics in cardiogenic shock: results from the OptimaCC trial. Eur J Heart Fail., DOI: 10.1002/ejhf.1600
8. van Lier (2020), Promotion of vascular integrity in sepsis through modulation of bioactive adrenomedullin and dipeptidyl peptidase 3, J. Intern. Med., DOI: doi.org/10.1111/joim.13220
9. Deniau et al. (2019), Circulating dipeptidyl peptidase is a myocardial depressant factor: dipeptidyl peptidase 3 inhibition rapidly and sustainably improves haemodynamics. Eur J Heart Fail. DOI : 10.1002/ejhf.1601
10. Dépret et al.(2020) Circulating dipeptidyl peptidase-3 at admission is associated with circulatory failure, acute kidney injury and death in severely ill burn patients. Crit Care , DOI: https://doi.org/10.1186/s13054-020-02888-5
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About SphingoTec
SphingoTec GmbH ("SphingoTec"; Hennigsdorf near Berlin, Germany) develops and markets innovative in vitro diagnostic (IVD) tests for novel and proprietary biomarkers for the diagnosis, prediction and monitoring of acute medical conditions, such as sepsis, acute heart failure, circulatory shock, and acute kidney injury in order to support patient management and provide guidance for treatment strategies. SphingoTec's proprietary biomarker portfolio includes bioactive Adrenomedullin (bio-ADM), a biomarker for real-time assessment of endothelial function in conditions like sepsis or congestive heart failure, Proenkephalin (penKid), a biomarker for real-time assessment of kidney function, and Dipeptidyl Peptidase 3 (DPP3), a biomarker for cardiac depression. IVD tests for SphingoTec’s proprietary biomarkers are made available as sphingotest® microtiter plate tests as well as point-of-care tests on the Nexus IB10 immunoassay platform by SphingoTec’s subsidiary Nexus Dx Inc. (San Diego, CA, USA) alongside a broad menu of established and commonly used tests for acute and critical care. www.sphingotec.com
About DPP3
sphingotest® DPP3 measures Dipeptidyl peptidase 3 an active enzyme which, when released into the blood, inactivates Angiotensin II, a hormone that is important for heart function. The depletion of Angiotensin II affects the renin-angiotensin-aldosterone system (RAAS), ultimately leading to cardiovascular depression and reduced vascular tone, a deadly combination in need of selective treatment strategies. The DPP3 release is a newly identified disease mechanism explaining short-term organ failure in critically ill patients. Early identification of DPP3 release may allow better patient stratification and earlier therapy escalation to improve outcomes.
Press contact
Ruxandra Lenz
Sr. Manager Marketing and Communications
SphingoTec GmbH
Neuendorfstr. 15 A
16761 Hennigsdorf
Tel. +49-3302-20565-0
press@sphingotec.com
www.sphingotec.com

A new peer-reviewed study in Physiological Reports is the first to evaluate Proenkephalin A 119-159 (penKid) for kidney functional reserve (KFR) assessment, a stress test designed to reveal loss of kidney capacity that may not be apparent from routine blood tests. Within that method, penKid stood out: its dynamic had a far wider range after a protein stimulus than cystatin C (44.2% vs. 10.5% median fractional change) while reaching its maximal response within approx. two hours after protein stimulation. The results extend the published evidence for penKid beyond acute kidney injury into a potential complementary application: assessing kidney functional reserve. Hennigsdorf, Germany – October 6, 2026 – penKid has been evaluated for the first time as a marker of kidney functional reserve (KFR): a new study in Physiological Reports (1) found that its response spanned a much wider range than cystatin C and creatinine clearance after a protein stimulus. The study in 62 participants marks the first published evaluation of penKid for this use. Clinical context and unmet need Kidney function may appear normal on a standard blood test until a large portion of capacity has already gone. Kidney functional reserve testing addresses this gap by measuring how much a kidney's filtration rate can still rise in response to a stimulus, most commonly a protein meal. Once that reserve narrows, the kidney has less room to compensate for future stress such as major surgeries. The study authors note that reserve testing is rarely used in clinical practice, largely because the reference method used, creatinine clearance, is cumbersome, requiring blood and urine collection, can be difficult to perform outside specialized settings, and is affected by processes in the kidney unrelated to filtration itself. Study design and key findings Researchers at the University of New South Wales and Prince of Wales Hospital in Sydney conducted the study in 62 participants: 40 patients having heart surgery, and 22 healthy people, including volunteers, kidney donors, and patients who had a kidney auto-transplant. Participants drank a protein shake, followed by hourly collection of blood samples over a five hour-period. Urine samples were also collected for creatinine clearance testing. After a high protein intake, kidney filtration increases for a few hours: this "extra work" is what the methods were designed to measure. PenKid showed the largest dynamic response, with a median fractional increase of 44% from baseline compared with 30% for creatinine clearance and only about 10% for cystatin C. Unlike creatinine clearance, penKid differentiated healthy participants from cardiac surgery patients, who had a lower KFR. The study also found penKid measurements to be more homogeneous than creatinine clearance measurements, indicating greater consistency across assessments. PenKid was also fast, reaching its peak functional response in about two hours, similar in timing to a two-hour diabetes test (oral glucose tolerance test). Implications for clinical practice Beyond its wider dynamic range, the authors highlight practical advantages specific to penKid-based functional reserve testing: no urine collection is needed, minimal fasting is required, and penKid enables near real-time assessment of kidney functional reserve from blood samples alone. These features suggest penKid may offer a fast and simple alternative to assess how much reserve an individual patient has. "PenKid gave us a fast, consistent read on how much filtration capacity a kidney still has in reserve," said Prof. Zoltan H. Endre, corresponding author of the study, Department of Nephrology, Prince of Wales Hospital, and School of Clinical Medicine, University of New South Wales, Sydney. "A signal that's clear, captured that quickly, turns a kidney stress test from a research tool into something a clinic could actually use." About penKid, scientific insights PenKid is a biomarker for real-time assessment of kidney function. Unlike creatinine, penKid levels are not influenced by inflammation or factors such as age or sex, and prior studies show penKid can detect acute kidney injury (AKI) up to 48 hours before conventional criteria are met (2,3). The new Physiological Reports study provides data for another, complementary application: measuring kidney functional reserve to identify subclinical kidney disease. About SphingoTec SphingoTec GmbH ("SphingoTec"; Hennigsdorf near Berlin, Germany) is a biomarker company focusing on the out-licensing of innovative critical care solutions for diagnosing, predicting, and monitoring acute medical conditions. SphingoTec develops its biomarkers to the commercial stage and partners with IVD companies to make them available on different IVD platforms. SphingoTec's proprietary biomarker portfolio includes Proenkephalin A 119-159 (penKid), a biomarker for the assessment of kidney function in critical diseases, and bioactive Adrenomedullin 1-52 (bio-ADM), a biomarker for the assessment of endothelial function in conditions like acute heart failure. Discover more on www.sphingotec.com References (1) Rodrigues, C. E. et. al. (2026). Plasma proenkephalin-a facilitates measurement of human kidney functional reserve: From healthy kidney donors to polymorbid patients. Physiological Reports, 14, e71083. https://doi.org/10.14814/phy2.71083 . (2) Caironi P, et al. (2018) Circulating Proenkephalin, Acute Kidney Injury, and Its Improvement in Patients with Severe Sepsis or Shock.; https://doi.org/10.1373/clinchem.2018.288068 (3) Rosenqvist M, et. al. (2019) Proenkephalin a 119-159 (penKid) - a novel biomarker for acute kidney injury in sepsis: an observational study. BMC Emerg Med, doi: 10.1186/s12873-019-0283-9. Media Contact: Email: press@sphingotec.com Phone +49-3302-20565-0 SphingoTec GmbH Neuendorfstr. 15A 16761 Hennigsdorf, Germany

In a prospective, real-world study of 1,436 critically ill ICU patients, proenkephalin A 119–159 (penKid) provided clinically relevant information across AKI severity and during kidney replacement therapy (KRT). PenKid addressed a key unmet need in KRT management by identifying, with greater precision than standard biomarkers, patients at high risk of KRT liberation failure – helping to avoid stopping therapy too early. The findings support a future role for penKid in helping to standardize one of the few intensive care processes where the need for better decision support is widely acknowledged and current tools remain insufficient. Hennigsdorf, Germany – August 27, 2026 – SphingoTec GmbH announces the publication of new real-world data on proenkephalin A 119–159 (penKid) in critically ill patients. The data, published in Annals of Intensive Care, add to the growing body of evidence supporting penKid as a functional biomarker for kidney function and help inform clinical decision-making in AKI and KRT (1). In a prospective observational study at Heidelberg University Hospital, penKid was measured in 1,436 critically ill patients, including 138 patients receiving KRT for liberation analyses. The findings showed that penKid rose with AKI severity and, unlike serum creatinine and urine output, distinguished stage 3 AKI patients with and without an acute KRT requirement. In contrast to serum creatinine, penKid also differentiated acute KRT patients from those with pre-existing kidney failure and on chronic hemodialysis prior ICU admission, even while KRT treatment was ongoing (1). The study further showed that penKid levels increased progressively from the start of KRT, while serum creatinine decreased under treatment. Following successful liberation from KRT, penKid declined, whereas higher levels were seen in cases of liberation failure. In multivariable analysis, penKid was the strongest independent predictor of liberation failure and outperformed serum creatinine. A penKid cut-off of ≥250 pmol/L provided more than 90% specificity for liberation failure (1). By identifying patients at high risk of unsuccessful liberation, penKid may help clinicians make KRT discontinuation decisions more objectively, reduce the risk of stopping therapy too early, and support more standardized decision-making across critical care settings. “These data are important because they address a real-world clinical problem: how to better assess kidney function and support KRT decisions when standard markers fall short,” said Deborah Bergmann, CEO of SphingoTec. “penKid provides clinicians with an objective, real-time measurable parameter that may help support more informed and consistent kidney-related decisions in critical care.” Christian Nusshag, MD, Department of Nephrology, Heidelberg University Hospital, said: “Current markers often leave clinicians with an incomplete picture. Our findings suggest that penKid may help standardize decision-making by providing additional, actionable information on kidney integrity and recovery.” About penKid, scientific insights PenKid is a biomarker that enables real-time assessment of kidney function. Unlike conventional markers such as serum creatinine, penKid levels are not influenced by inflammation or other confounding factors like age or sex. Studies have shown that penKid allows earlier detection of AKI, predicting changes in serum creatinine up to 48 hours before conventional diagnostic criteria are met. This early detection capability is particularly valuable in critically ill patients, including those with sepsis or septic shock. Additionally, penKid has shown potential for monitoring renal recovery under KRT and could help predict successful liberation from KRT. About SphingoTec SphingoTec GmbH ("SphingoTec"; Hennigsdorf near Berlin, Germany) is a biomarker company focusing on the out-licensing of innovative critical care solutions for diagnosing, predicting, and monitoring acute medical conditions. SphingoTec develops its biomarkers to the commercial stage and partners with IVD companies to make them available on different IVD platforms. SphingoTec's proprietary biomarker portfolio includes Proenkephalin A 119-159 (penKid), a biomarker for the assessment of kidney function in critical diseases, and bioactive Adrenomedullin 1-52 (bio-ADM), a biomarker for the assessment of endothelial function in conditions like acute heart failure. Discover more on www.sphingotec.com References (1) Gabriel DC, Sauer P, Happel R, et al. Proenkephalin A for Assessing Kidney Integrity and Guiding KRT Liberation Decisions in Critically Ill Patients. Annals of Intensive Care. 2026. DOI: 10.1016/j.aicoj.2026.100113. Media Contact: Email: press@sphingotec.com Phone +49-3302-20565-0 SphingoTec GmbH Neuendorfstr. 15A 16761 Hennigsdorf, Germany
