Proenkephalin Peptide Levels May Help Predict Heart Failure Outcomes and Kidney Risks
Nikhil Prasad Fact checked by:Thailand Medical News Team Apr 14, 2025 1 day, 9 hours, 3 minutes ago
Medical News: Breakthrough Biomarker Could Transform How Doctors Manage Heart Failure and Kidney Function
Researchers in Greece have spotlighted a little-known peptide, Proenkephalin 119–159 (PENK119–159), that could play a game-changing role in predicting heart failure severity, treatment outcomes, and even the onset of kidney damage. This new focus on PENK119–159 could reshape how hospitals worldwide assess and treat patients with heart failure.
Proenkephalin Peptide Levels May Help Predict Heart Failure Outcomes and Kidney Risks
Heart failure remains a life-threatening condition affecting millions, with high hospital readmission and death rates. While current biomarkers like natriuretic peptides are used to diagnose and monitor heart failure, experts believe they don’t paint the full picture. This
Medical News report covers a new scientific review that explores how PENK119–159—a molecule from the body’s own opioid system—may offer deeper insights into the disease and its progression.
The research was conducted by scientists from Attikon University Hospital and the National and Kapodistrian University of Athens, the University of Western Macedonia, and AHEPA University Hospital at the Aristotle University of Thessaloniki.
What is Proenkephalin 119–159 and Why Does It Matter
PENK119–159 is a stable fragment derived from a larger protein called proenkephalin, which in turn produces active enkephalins—natural opioids that the body uses for pain control and many other biological processes. Unlike its parent molecules, PENK119–159 does not perform biological tasks itself, but because it is easier to detect in blood, it has become a valuable marker indicating activity of the opioid system in tissues like the heart and kidneys.
Recent studies have shown that levels of PENK119–159 are significantly higher in patients with worsening heart failure. This peptide appears to track closely with worsening kidney function and may predict short- and long-term risks of death, repeat hospitalizations, and disease progression.
The Role of the Body’s Opioid System in Heart Health
Traditionally thought to be limited to pain and the brain, enkephalins and their receptors are actually present in the heart muscle, nerve fibers around the heart, and the kidneys. In patients with heart failure, the body’s opioid system becomes highly active—possibly as an attempt to counteract stress and overactive sympathetic nervous system responses. Researchers found that opioid receptors are distributed across various regions of the heart and may influence calcium handling, nerve signaling, and even hormonal secretion from the adrenal glands. Increased PENK119–159 levels may therefore be a reflection of this heightened opioid system activity, indicating more severe disease and physiological stress.
Key Study Findings in Depth
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Several recent observational studies analyzed PENK119–159 levels in both acute and chronic heart failure patients. Patients with higher levels of this peptide consistently showed:
-Worse left ventricular function
-Higher NYHA (New York Heart Association) functional class, indicating more severe symptoms
-Higher levels of natriuretic peptides (like BNP and NT-proBNP)
-Greater risk of death, kidney injury, or needing to be hospitalized again
-A clear relationship with kidney function markers like creatinine, eGFR, urea, and even tubular injury indicators like NGAL and KIM-1
One study showed that PENK119–159 levels above 83 pmol/L were linked to dramatically worse outcomes, while those below 48.3 pmol/L pointed to better recovery odds. In some patients, rising PENK119–159 levels even preceded the development of acute kidney injury, suggesting it could serve as an early warning sign before traditional markers like creatinine start to rise.
Implications for the Future of Heart Failure Management
By measuring PENK119–159 levels in the blood, clinicians might be able to more accurately identify which patients are at highest risk for deterioration—particularly those who may experience kidney complications alongside heart failure. This could lead to more personalized and earlier interventions, such as adjustments in medications or fluid management strategies, potentially improving survival and reducing hospitalizations.
While more large-scale clinical trials are needed, the consistent findings across existing studies point to PENK119–159 as a powerful new tool in the fight against heart failure and cardiorenal syndrome.
Conclusion
This new focus on PENK119–159 offers hope for patients with heart failure, a condition notorious for its unpredictability and high treatment burden. Unlike older markers that mainly reflect volume overload or cardiac stress, PENK119–159 captures the deeper biological shifts occurring in both the heart and kidneys. If further validated, this peptide could change clinical protocols and offer more timely, targeted care to those who need it most. Understanding and monitoring this biomarker may help doctors intervene before irreversible damage occurs, and potentially improve quality of life and survival for countless patients.
The study findings were published in the peer reviewed Journal of Clinical Medicine.
https://www.mdpi.com/2077-0383/14/8/2657
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