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Proenkephalin as a biomarker correlates with acute kidney injury: a systematic review with meta-analysis and trial sequential analysis

Lin, Li-Chun ; Chuan, Min-Hsiang ; Liao, Hung-Wei ; Ng, Leong L ; Magnusson, Martin LU orcid ; Jujic, Amra LU ; Pan, Heng-Chih ; Wu, Vin-Cent and Forni, Lui G (2023) In Critical Care 27.
Abstract
Background
Proenkephalin A 119-159 (PENK) is freely filtered in the glomerulus with plasma levels correlating with glomerular filtration rate. Therefore, PENK has been proposed as an early indicator of acute kidney injury (AKI) although its performance is dependent on the clinical setting. This meta-analysis aimed to investigate the correlation between PENK levels and the development of AKI.

Methods
We conducted a comprehensive search on the PubMed, Embase, Cochrane databases, the website ClinicalTrials.gov and Cnki.net until June 26, 2023. Summary receiver operating characteristic (SROC) curves were used to amalgamate the overall test performance. Diagnostic odds ratio (DOR) was employed to compare the diagnostic accuracy... (More)
Background
Proenkephalin A 119-159 (PENK) is freely filtered in the glomerulus with plasma levels correlating with glomerular filtration rate. Therefore, PENK has been proposed as an early indicator of acute kidney injury (AKI) although its performance is dependent on the clinical setting. This meta-analysis aimed to investigate the correlation between PENK levels and the development of AKI.

Methods
We conducted a comprehensive search on the PubMed, Embase, Cochrane databases, the website ClinicalTrials.gov and Cnki.net until June 26, 2023. Summary receiver operating characteristic (SROC) curves were used to amalgamate the overall test performance. Diagnostic odds ratio (DOR) was employed to compare the diagnostic accuracy of PENK with other biomarkers. Quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria.

Results
We incorporated 11 observational studies with 3969 patients with an incidence of AKI of 23.4% (929 out of 3969 patients) with the best optimal cutoff value of PENK for early detection of AKI being 57.3 pmol/L. The overall sensitivity and specificity of PENK in identifying AKI were 0.69 (95% CI 0.62–0.75) and 0.76 (95% CI 0.68–0.82), respectively. The combined positive likelihood ratio (LR) stood at 2.83 (95% CI 2.06–3.88), and the negative LR was 0.41 (95% CI 0.33–0.52). The SROC curve showcased pooled diagnostic accuracy of 0.77 (95% CI 0.73–0.81). Interestingly, patients with a history of hypertension or heart failure demonstrated a lower specificity of PENK in correlating the development of AKI.

Conclusion
Our results indicate that PENK possesses significant potential as a biomarker for the early detection of the development of AKI, using a cutoff point of 57.3 pmol/L for PENK. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Critical Care
volume
27
article number
481
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85178954699
  • pmid:38057904
ISSN
1364-8535
DOI
10.1186/s13054-023-04747-5
language
English
LU publication?
yes
id
0b9d977f-351e-45fc-9902-2c8fd8a1f280
date added to LUP
2023-12-07 09:18:10
date last changed
2024-03-08 03:00:07
@article{0b9d977f-351e-45fc-9902-2c8fd8a1f280,
  abstract     = {{Background<br/>Proenkephalin A 119-159 (PENK) is freely filtered in the glomerulus with plasma levels correlating with glomerular filtration rate. Therefore, PENK has been proposed as an early indicator of acute kidney injury (AKI) although its performance is dependent on the clinical setting. This meta-analysis aimed to investigate the correlation between PENK levels and the development of AKI.<br/><br/>Methods<br/>We conducted a comprehensive search on the PubMed, Embase, Cochrane databases, the website ClinicalTrials.gov and Cnki.net until June 26, 2023. Summary receiver operating characteristic (SROC) curves were used to amalgamate the overall test performance. Diagnostic odds ratio (DOR) was employed to compare the diagnostic accuracy of PENK with other biomarkers. Quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria.<br/><br/>Results<br/>We incorporated 11 observational studies with 3969 patients with an incidence of AKI of 23.4% (929 out of 3969 patients) with the best optimal cutoff value of PENK for early detection of AKI being 57.3 pmol/L. The overall sensitivity and specificity of PENK in identifying AKI were 0.69 (95% CI 0.62–0.75) and 0.76 (95% CI 0.68–0.82), respectively. The combined positive likelihood ratio (LR) stood at 2.83 (95% CI 2.06–3.88), and the negative LR was 0.41 (95% CI 0.33–0.52). The SROC curve showcased pooled diagnostic accuracy of 0.77 (95% CI 0.73–0.81). Interestingly, patients with a history of hypertension or heart failure demonstrated a lower specificity of PENK in correlating the development of AKI.<br/><br/>Conclusion<br/>Our results indicate that PENK possesses significant potential as a biomarker for the early detection of the development of AKI, using a cutoff point of 57.3 pmol/L for PENK.}},
  author       = {{Lin, Li-Chun and Chuan, Min-Hsiang and Liao, Hung-Wei and Ng, Leong L and Magnusson, Martin and Jujic, Amra and Pan, Heng-Chih and Wu, Vin-Cent and Forni, Lui G}},
  issn         = {{1364-8535}},
  language     = {{eng}},
  month        = {{12}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Critical Care}},
  title        = {{Proenkephalin as a biomarker correlates with acute kidney injury: a systematic review with meta-analysis and trial sequential analysis}},
  url          = {{http://dx.doi.org/10.1186/s13054-023-04747-5}},
  doi          = {{10.1186/s13054-023-04747-5}},
  volume       = {{27}},
  year         = {{2023}},
}