Researchers Link Low Levels of Pro-Enkephalin to Future Breast Cancer in Healthy Women
sphingotec announces the publication of trial results showing the strong association between low pro-enkephalin (pro-ENK) levels in plasma and incident breast cancer
Cambridge, Mass. – July 15, 2015
– sphingotec LLC announced today that the results of two studies examining the association between proenkephalin (pro-ENK) and incident breast cancer were published online in the Journal of Clinical Oncology. The studies, which were conducted by researchers at Skåne University Hospital in Malmö, Sweden and together encompass almost 3,500 subjects, demonstrated a strong association between low plasma concentration of the opioid precursor peptide pro-ENK and increased breast cancer risk in middle-aged and post-menopausal women independent from other possible risk factors.
Although experimental studies have established that enkephalins and related opioid hormones can inhibit the growth of cancer cells, these are the first studies to investigate whether plasma concentration of pro-ENK can predict near-term breast cancer risk in healthy women. The strong association between concentrations of pro-ENK and incident breast cancer found during these studies indicates that pro-ENK is a viable tool for predicting breast cancer risk.
The results represent a potential breakthrough in helping women without a known family history of breast cancer understand their own risk. Current tools such as the GAIL risk score are helpful, but the parameters included in the score are non-modifiable, have only weak prognostic power and do not address an individual’s risk. And while mammography is effective at detecting early stage breast cancer, there is ongoing concern about over-diagnosis and missed cases. There is a great need for biomarkers that can identify women at highest risk so that appropriate interventional measures can be taken to prevent clinical manifestation of life-threatening breast cancer.
“Our goal is to prevent deaths related to breast cancer,” said Dr. Andreas Bergmann, founder and CEO for sphingotec. “We have now identified two promising biomarkers to achieve this goal: proneurotensin* (pro-NT) and proenkephalin, which have been demonstrated now in two independent cohorts to predict risk in healthy women. The results of these studies imply great promise for the future of breast cancer prevention. We believe these findings will aid in helping women better understand their breast cancer risk so they can take the appropriate measures for preventing this devastating disease.”
To conduct the first study, Melander et al. measured pro-ENK in fasting plasma from 1,929 healthy women with a mean age of 59 years old participating in the Malmö Diet and Cancer Study (MDCS) and used Cox proportional hazards models to relate pro-ENK to incidence of breast cancer during 15 years of follow up. In the second study, using a case-control design, they sampled 1,569 women from the Malmö Preventive Project with a mean age of 70 years old and used multivariate adjusted logistic regression models to relate pro-ENK and to risk of breast cancer during the observation period.
Results of this study appear online in the Journal of Clinical Oncology.
*Melander et al. JAMA. 2012;308(14):1469-1475
Authors: Olle Melander, Marju Melander, Jonas Manjer, Peter Almgren, Peter Nilsson, Gunnar Engström, Bo Hedblad, Signe Borquist, Ute Kilger, Jennifer Suhr, Oliver Hartmann, Joachim Struck, Andreas Bergmann and Mattias Belting
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