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
• New ELISA sphingotest® penKid® enables widespread measurement of the kidney function biomarker Proenkephalin 119-159 (penKid) using standard laboratory equipment. • Only available test to match SphingoTec’s reference chemiluminescence assay, developed with patented high-sensitivity technology to provide consistent results across platforms. Hennigsdorf/Berlin, Germany, April 28 2026 - SphingoTec GmbH announces the launch of the ELISA sphingotest® penKid®, a new assay designed to make testing of its proprietary biomarker broadly accessible to research laboratories and pharmaceutical partners. Providing ease-of-use and precision, the test facilitates large-scale investigations of human kidney function in both acute and broader clinical research contexts. Responding to growing research interest The launch follows increasing demand from the scientific community to study penKid - a biomarker reflecting the current state of kidney function in critical care environments. While SphingoTec’s high-sensitivity sphingotest® penKid® assay serves as the reference method for clinical research and third-party IVD assays, the assay technology requiring dedicated equipment was not easily adoptable in research laboratories. The new ELISA sphingotest® penKid® now allows researchers worldwide to benefit from SphingoTec’s patented detection technology using standard photometers, extending penKid testing capability to a wider range of laboratories. Proven performance and data continuity The ELISA sphingotest® penKid® has been developed to achieve excellent correlation with SphingoTec’s reference chemiluminescence assay, ensuring consistent, high-quality results across different assay platforms. Both methods share the same underlying technology capable of detecting penKid concentrations in the picomolar range. Thanks to this technology transfer, researchers can rely on the same analytical precision and reliability that supported the clinical studies establishing penKid as a valuable kidney function biomarker. The assay’s robust design and German manufacturing ensure durable consistency and reproducibility. With this research-use ELISA, SphingoTec responds to the increasing availability of non-validated assays and encourages researchers to not compromise assay quality and performance to ensure trustworthy results - since data from non-validated tests may reflect assay limitations rather than the true performance of the penKid biomarker. Complementary approaches for clinical use and scientific exploration SphingoTec pursues its commercial strategy for the biomarker penKid through strategic out-licensing partnerships such as Boditech Med, which has developed an IVDR-certified assay for routine clinical use and rapid diagnostics. The newly launched ELISA sphingotest® penKid® represents a complementary initiative, specifically designed to support high-throughput clinical and translational research. Through this dual approach, SphingoTec reaffirms its commitment to fostering scientific collaboration and promoting the broader exploration of penKid across diverse research settings. “Developing the ELISA sphingotest® penKid® reflects our long-term commitment to improving critical care diagnostics,” said Deborah Bergmann, Managing Director and CEO of SphingoTec GmbH. “Beyond its currently validated clinical applications, we see strong potential for penKid to support research and improve diagnostics in other fields where kidney function is relevant. By encouraging scientists worldwide to incorporate penKid into their studies and clinical programs, we aim to accelerate innovation and advance best-fit diagnostic solutions that ultimately improve patient care.” 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 sepsis. Discover more on www.sphingotec.com Media Contact: Email: press@sphingotec.com Phone +49-3302-20565-0 SphingoTec GmbH Neuendorfstr. 15A 16761 Hennigsdorf, Germany
• PenKid surpasses serum creatinine on Day 1 post-transplant in detecting delayed graft function (DGF), with an AUROC of 0.87 versus 0.56 for creatinine. • PenKid differentiates slow graft function (SGF) from DGF up to 8 days earlier than current methods, supporting more timely clinical decisions. • PenKid levels remain unaffected by kidney replacement therapy (KRT), allowing for more accurate assessment of kidney function. • Independent validation in transplant cohort from Australia confirms performance and broad applicability. Hennigsdorf/Berlin, Germany, July 1, 2025 - Diagnostic company SphingoTec GmbH (“SphingoTec”) announces a landmark study (1) published in Transplant International, led by Heidelberg University Hospital in Germany in collaboration with researchers from Sydney, Australia, which identifies Proenkephalin A 119-159 (penKid) as a reliable biomarker for early and precise assessment of graft function trajectories following kidney transplantation. The research demonstrates that PenKid not only identifies patients at risk for DGF significantly earlier than traditional markers but also distinguishes between slow and delayed graft function with remarkable accuracy, offering clinicians a valuable new tool for patient management. The study prospectively evaluated 159 consecutive kidney transplant recipients at Heidelberg University Hospital and validated findings in an independent cohort from Sydney. PenKid consistently outperformed serum creatinine (SCr) in predicting graft function trajectories, particularly in the critical early post-transplant period. Notably, PenKid’s ability to remain unaffected by KRT—a treatment for severe kidney dysfunction—further sets it apart from SCr, which can be influenced by non-renal factors and KRT itself, thereby enhancing the reliability of graft function assessment. Multivariate analysis confirmed PenKid as the strongest independent predictor of both short-term graft function and 30-day outcomes, underscoring its clinical utility for early risk stratification. The biomarker’s superior granularity allows for nuanced classification of DGF severity, supporting more informed decisions regarding the initiation of dialysis or biopsy and offering potential for individualized patient care. With these findings, penKid steps forward as a practical addition to the transplant clinician’s toolkit, promising to sharpen decision-making for optimal outcomes. Its adoption could help transplant teams act with greater confidence and precision, ultimately strengthening the standard of care in kidney transplantation. ## References 1. Benning L et al. (2025) Proenkephalin A 119-159 in Kidney Transplantation: A Novel Biomarker for Superior Tracking of Graft Function Trajectories. Transpl. Int. 38:14366. doi: 10.3389/ti.2025.14366 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, commercially available on diagnostic platforms AFIAS and Nexus IB10 and bioactive Adrenomedullin 1-52 (bio-ADM), a biomarker for the assessment of endothelial function in conditions like sepsis. Discover more on www.sphingotec.com Contact : Ruxandra Lenz Marketing and Communication SphingoTec GmbH Phone +49-3302-20565-0 Email: press@sphingotec.com