The Biomarkers bio-ADM and DPP3 Complement Post-Cardiac Surgery Diagnostics to Early Detect Organ Failure

• Post-surgical increase of endothelial function biomarker bioactive adrenomedullin (bio-ADM) concentrations predicts organ dysfunction.
• Bio-ADM may help identify patients with an increased risk of developing prolonged vasopressor dependence and prolonged ICU stay after cardiac surgery.
• Increased blood concentrations of cardiac depressant factor dipeptidyl peptidase 3 (DPP3) are related to the complexity and duration of the intervention.

Hennigsdorf, Germany, March 24, 2022 - The diagnostic company SphingoTec GmbH (SphingoTec) announces new evidence supporting the use of innovative biomarkers in the early identification of organ dysfunction and risk stratification of cardiac surgery patients (1). Despite many serious post-operative complications (2), there are currently limited tools available for the early identification of organ dysfunction in these patients (3,4). 

Scientists from the Radboud University Medical Center have analyzed the predictive value of bio-ADM and DPP3 for short-term outcomes in a prospective study in cardiac surgery patients. Bio-ADM and DPP3 represent two distinct molecular pathways involved in the development of circulatory shock (5). Compromised hemodynamics after surgery triggers the release of the hormone bio-ADM, a key regulator of endothelial barrier function and vascular tone. The current data shows that bio-ADM at day two after ICU admission effectively differentiated between high-risk and low-risk patients for developing organ failure. 

The study data also confirmed the independency of a second pathophysiological process, the release of DPP3 upon cell death. Surgery acts as an additional factor leading to an increase in DPP3 in the bloodstream, which is mainly related to tissue injury and the extent of the procedure. Therefore, elevated levels of DPP3 decrease shortly after the surgery. Not surgery-induced and persistently high concentration of DPP3 signals impaired tissue perfusion and high risk for organ failure (5).  

Dr. Andreas Bergmann, founder and CEO of SphingoTec, added, “Cardiac surgery is often accompanied by postoperative complications. By using the innovative biomarkers, clinicians can improve the risk stratification provided by conventional risk scores and improve their patient management.”





References: 

1. van Lier et al. The value of bioactive adrenomedullin and dipeptidyl peptidase 3 to predict short-term unfavourable outcomes after cardiac surgery: A prospective cohort study. Eur J Anaesthesiol. 2022 Apr 1;39(4):342-351. doi: 10.1097/EJA.0000000000001662.
2. Nearman et al. Perioperative complications of cardiac surgery and postoperative care. Crit Care Clin 2014; 30:527–555.
3. Paparella et al. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg 2002; 21:232–244.
4. Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology 2002; 97:215–252
5. van Lier D, Kox M, Pickkers P. Promotion of vascular integrity in sepsis through modulation of bioactive adrenomedullin and dipeptidyl peptidase 3. J Intern Med 2020; 289:792–806.


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. SphingoTec's proprietary biomarker portfolio includes bioactive Adrenomedullin (bio-ADM), a biomarker for real-time assessment of endothelial function in conditions like sepsis, and Proenkephalin (penKid), a biomarker for real-time assessment of kidney function. Dipeptidyl Peptidase 3 (DPP3), a biomarker for cardiac depression. IVD tests for SphingoTec’s 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). The Nexus IB10 portfolio is complemented by established and commonly used biomarker tests for acute and critical care such as PCT, Troponin, NT-proBNP, D-Dimer, TSH, and others.


Media contact SphingoTec: 
Ruxandra Lenz
Sr. Manager Marketing and Communications
SphingoTec GmbH
Neuendorfstr. 15 A
16761 Hennigsdorf
Tel. +49-3302-20565-0


October 5, 2026
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
August 27, 2026
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