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

Shock. 2020 Sep;54(3):308-314. doi: 10.1097/SHK.0000000000001510.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Critical Illness
  • Enkephalins / blood*
  • Humans
  • Inulin / blood
  • Iohexol / pharmacokinetics*
  • Kidney / metabolism
  • Kidney Function Tests
  • Middle Aged
  • Prospective Studies
  • Protein Precursors / blood*
  • Sepsis / blood*
  • Shock, Septic / blood*


  • Enkephalins
  • Protein Precursors
  • proenkephalin
  • Iohexol
  • Inulin
  • preproenkephalin