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Renal elimination and eGFR prediction of proenkephalin

Sigurjonsson, Johann LU orcid ; Nyman, Ulf LU ; Bjursten, Henrik LU and Grubb, David LU (2025) In Scandinavian Journal of Clinical and Laboratory Investigation p.1-6
Abstract

Proenkephalin (PENK) is assumed to be freely filtered by the glomerulus, thus potentially useful for estimating glomerular filtration rate (eGFR). Recently developed eGFR-equation based on PENK and creatinine has not been validated against existing cystatin C-based equations. This study aimed to test the hypothesis of free filtration of PENK. Also, the PENK-creatinine based eGFR-equation was validated against cystatin C. Plasma concentrations of PENK, creatinine and cystatin C were determined in arterial and renal venous blood samples collected from 70 patients undergoing transcatheter aortic valve implantation (TAVI). The renal elimination ratio (RER) of PENK (RERPENK) was calculated and compared to the RER of creatinine... (More)

Proenkephalin (PENK) is assumed to be freely filtered by the glomerulus, thus potentially useful for estimating glomerular filtration rate (eGFR). Recently developed eGFR-equation based on PENK and creatinine has not been validated against existing cystatin C-based equations. This study aimed to test the hypothesis of free filtration of PENK. Also, the PENK-creatinine based eGFR-equation was validated against cystatin C. Plasma concentrations of PENK, creatinine and cystatin C were determined in arterial and renal venous blood samples collected from 70 patients undergoing transcatheter aortic valve implantation (TAVI). The renal elimination ratio (RER) of PENK (RERPENK) was calculated and compared to the RER of creatinine (RERcrea). RER constitutes the single-pass renal elimination of a molecule, calculated as the arteriovenous concentration difference divided by the arterial concentration. For eGFR validations, the CAPA (cystatin C) and LMR (creatinine) equations were used. RERPENK (23.7 ± 9.6%) was approximately 10% higher than RERcrea (21.4 ± 5.8%). The PENK-creatinine equation overestimated GFR by 26,1% on average, compared to the mean of the LMR and CAPA equations. The relationship between RERPENK and RERcrea suggests free filtration and a slight degree of non-glomerular elimination of PENK. There was poor agreement between PENK and cystatin C derived eGFR-equations. PENK needs further evaluation as a predictor of GFR.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
biomarkers, creatinine, cystatin C, glomerular filtration rate, kidney function tests, predictive value of tests, Proenkephalin, renal clearance
in
Scandinavian Journal of Clinical and Laboratory Investigation
pages
1 - 6
publisher
Informa Healthcare
external identifiers
  • pmid:40493517
  • scopus:105007706575
ISSN
0036-5513
DOI
10.1080/00365513.2025.2512383
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
id
742ff2db-01f8-4c04-8eef-efa61f8c73f5
date added to LUP
2025-06-24 22:32:30
date last changed
2025-06-25 08:45:30
@article{742ff2db-01f8-4c04-8eef-efa61f8c73f5,
  abstract     = {{<p>Proenkephalin (PENK) is assumed to be freely filtered by the glomerulus, thus potentially useful for estimating glomerular filtration rate (eGFR). Recently developed eGFR-equation based on PENK and creatinine has not been validated against existing cystatin C-based equations. This study aimed to test the hypothesis of free filtration of PENK. Also, the PENK-creatinine based eGFR-equation was validated against cystatin C. Plasma concentrations of PENK, creatinine and cystatin C were determined in arterial and renal venous blood samples collected from 70 patients undergoing transcatheter aortic valve implantation (TAVI). The renal elimination ratio (RER) of PENK (RER<sub>PENK</sub>) was calculated and compared to the RER of creatinine (RER<sub>crea</sub>). RER constitutes the single-pass renal elimination of a molecule, calculated as the arteriovenous concentration difference divided by the arterial concentration. For eGFR validations, the CAPA (cystatin C) and LMR (creatinine) equations were used. RER<sub>PENK</sub> (23.7 ± 9.6%) was approximately 10% higher than RER<sub>crea</sub> (21.4 ± 5.8%). The PENK-creatinine equation overestimated GFR by 26,1% on average, compared to the mean of the LMR and CAPA equations. The relationship between RER<sub>PENK</sub> and RER<sub>crea</sub> suggests free filtration and a slight degree of non-glomerular elimination of PENK. There was poor agreement between PENK and cystatin C derived eGFR-equations. PENK needs further evaluation as a predictor of GFR.</p>}},
  author       = {{Sigurjonsson, Johann and Nyman, Ulf and Bjursten, Henrik and Grubb, David}},
  issn         = {{0036-5513}},
  keywords     = {{biomarkers; creatinine; cystatin C; glomerular filtration rate; kidney function tests; predictive value of tests; Proenkephalin; renal clearance}},
  language     = {{eng}},
  pages        = {{1--6}},
  publisher    = {{Informa Healthcare}},
  series       = {{Scandinavian Journal of Clinical and Laboratory Investigation}},
  title        = {{Renal elimination and eGFR prediction of proenkephalin}},
  url          = {{http://dx.doi.org/10.1080/00365513.2025.2512383}},
  doi          = {{10.1080/00365513.2025.2512383}},
  year         = {{2025}},
}