Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Sep;54(3):308-314.
doi: 10.1097/SHK.0000000000001510.

Proenkephalin Compared to Conventional Methods to Assess Kidney Function in Critically Ill Sepsis Patients

Remi Beunders  1   2   3 , Roger van Groenendael  1   2   3   4 , Guus P Leijte  1   2   3 , Matthijs Kox  1   2   3 , Peter Pickkers  1   2   3
Affiliations

Proenkephalin Compared to Conventional Methods to Assess Kidney Function in Critically Ill Sepsis Patients

Remi Beunders et al. Shock. 2020 Sep.

Abstract

Background: 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, e.g., 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, has shown to represent steady-state GFR in patients with different severities of renal insufficiency. In this pilot study in non-steady-state critically ill patients, we 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.

Methods: Twenty-three critically ill patients with septic shock were included. Kidney function was determined using the Modification of Diet in Renal Disease formula (eGFRMDRD), Endogenous Creatinine Clearance (GFRECC), and iohexol plasma clearance (GFRiohexol) during a 6-h window. Plasma PENK concentrations were measured using the penKid immunoassay.

Results: The eGFRMDRD and GFRECC correlated with the GFRiohexol (R = 0.82, P < 0.0001 and R = 0.82, P < 0.0001 respectively); however, bias and variability were considerable: the eGFRMDRD overestimated the true GFR with 31 ± 35% (95% limits of agreement: -37% to 100%) and the GFRECC with 37 ± 49% (95% limits of agreement: -59% to 133%). Plasma PENK concentrations showed a very strong inverse correlation with the GFRiohexol (R = 0.90, P < 0.0001) which tended to be better compared with the correlation of eGFRMDRD (P = 0.06) and GFRECC (P = 0.08) with the GFRiohexol.

Conclusions: In this pilot study 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.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest.

Figures

Fig. 1
Fig. 1
Study procedures.
Fig. 2
Fig. 2
Bland-Altman plot of GFRMDRD and GFRiohexol.
Fig. 3
Fig. 3
Bland-Altman plot of GFRECC and GFRiohexol.
Fig. 4
Fig. 4
Correlation of plasma PENK concentrations with GFRiohexol.
See this image and copyright information in PMC

References

    1. Bellomo R, Ronco C, Mehta RL, Asfar P, Boisrame-Helms J, Darmon M, Diehl JL, Duranteau J, Hoste EAJ, Olivier JB, et al. Acute kidney injury in the ICU: from injury to recovery: reports from the 5th Paris International Conference. Ann Intensive Care 7 (1):49, 2017. - PMC - PubMed
    1. Pannu N, James M, Hemmelgarn B, Klarenbach S. Association between AKI, recovery of renal function, and long-term outcomes after hospital discharge. Clin J Am Soc Nephrol 8 (2):194–202, 2013. - PMC - PubMed
    1. Delanaye P, Cavalier E, Pottel H. Serum creatinine: not so simple!. Nephron 136 (4):302–308, 2017. - PubMed
    1. (KDIGO) KDIGO: Kidney disease: Improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2 (1):1–138, 2012.
    1. Sterner G, Frennby B, Mansson S, Nyman U, Van Westen D, Almen T. Determining ‘true’ glomerular filtration rate in healthy adults using infusion of inulin and comparing it with values obtained using other clearance techniques or prediction equations. Scand J Urol Nephrol 42 (3):278–285, 2008. - PubMed

Publication types