Proenkephalin Assesses True Glomerular Filtration Rate Accurately

The assessment of renal function in clinical practice remains challenging. Using creatinine to assess the glomerular filtration rate (GFR) is notoriously inaccurate, and determination of the true GFR, such as using inulin or iohexol, is laborious and not feasible in daily practice.

Proenkephalin (PENK) is a novel candidate biomarker for kidney function that is filtrated in the glomerulus, shown to represent steady-state GFR in patients with different severities of renal insufficiency and is reliably predictive for acute kidney injury in patients with severe burns. Although AKI is a major complication in critically ill patients, current diagnostic standard methods do not properly and timely diagnose impaired renal function.

Scientists at the Radboud University Medical Center (Nijmegen, the Netherlands) conducted a pilot study in non-steady-state critically ill patients, and compared plasma PENK concentrations with creatinine-based GFR assessments and validated both against the ‘true GFR’ measured using a gold standard method: iohexol plasma clearance.

The investigators included 23 critically ill patients with septic shock. Kidney function was determined using the Modification of Diet in Renal Disease formula (eGFR_MDRD), Endogenous Creatinine Clearance (GFR_ECC), and iohexol plasma clearance (GFR_iohexol) during a 6-hour window. Plasma PENK concentrations were measured using the penKid immunoassay (SphingoTec GmbH, Hennigsdorf Germany).

The scientists reported that the eGFR_MDRD and GFR_ECC correlated with the GFR_iohexol (R² = 0.82, p < 0.0001 and R² = 0.82, p < 0.0001 respectively), however bias and variability were considerable: the eGFR_MDRD overestimated the true GFR with 31 ± 35% (95% limits of agreement: -37 to 100%) and the GFR_ECC with 37 ± 49% (95% limits of agreement: -59 to 133%). Plasma PENK concentrations showed a very strong inverse correlation with the GFR_iohexol which tended to be better compared to the correlation of eGFR_MDRD and GFR_ECC with the GFR_iohexol.

Andreas Bergmann, PhD, CEO of Sphingotec, commented, "penKid is an early renal function biomarker that is not biased by co-morbidities while reflecting true GFR. penKid has been tested for the first time to identify ICU patients with severe burns that need rapid and aggressive intervention to prevent mortality caused by AKI.”

The authors concluded that in non-steady state critically ill sepsis patients, GFR appears to be more accurately reflected by plasma PENK concentrations compared to conventional creatinine-based methods. Therefore, PENK holds promise as an accurate and feasible biomarker to determine kidney function during non-steady-state conditions in the critically ill. The study was published ahead of print on January 21, 2020 in the journal SHOCK.

Related Links:
Radboud University Medical Center
SphingoTec GmbH