Proenkephalin as biomarker for acute renal injury - a systematic review

Recently published systematic review and meta-analysis aimed to investigate the correlation between Proenkephalin A 119-159 (PENK) levels and the development of acute kidney injury (AKI). The review incorporated 11 observational studies with 3969 patients, and the overall sensitivity and specificity of PENK in identifying AKI were found to be 0.69 and 0.76, respectively. The combined positive likelihood ratio (LR) stood at 2.83, and the negative LR was 0.41. The study also determined the optimal cutoff value of PENK for early detection of AKI to be 57.3 pmol/L, and the SROC curve showcased a pooled diagnostic accuracy of 0.77. Patients with a history of hypertension or heart failure demonstrated a lower specificity of PENK in correlating the development of AKI. Further analyses suggested that patients with heart failure and hypertension may result in a higher false-positive rate when using PENK as an early indicator of AKI.

Conclusion on PENK's Potential as a Biomarker for AKI

The study concluded 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. The article also highlighted the need for additional clinical trials and real-world studies to validate the utility of PENK as a biomarker for anticipating AKI onset. The findings from the systematic review and meta-analysis support the potential of PENK as a biomarker for incident AKI with high positive and negative likelihood ratios. Additionally, a distinct cutoff value for PENK was established, enhancing its utility in excluding the possibility of AKI.

Evaluation of Study Quality and Acknowledgement of Limitations

The study's conclusions are strengthened by a comprehensive evaluation of study quality by using the QUADAS-2 framework, as well as trial sequential analysis (TSA), which demonstrated that the required information size was exceeded, further supporting the notion that PENK is an effective biomarker for ruling out the presence of AKI based on negative levels of PENK. However, the study acknowledged several limitations, including moderate sample sizes across most studies, limited number of studies for extensive subgroup analysis, variations in PENK analysis methods, and potential influence of heart failure and hypertension on PENK's diagnostic accuracy.

Summary of Systematic Review and Meta-Analysis Findings

In summary, the systematic review and meta-analysis provide robust evidence of PENK's diagnostic accuracy for AKI and suggest its potential as a reliable biomarker for early detection, with the understanding that further research and validation in different clinical settings and patient subgroups are essential to enhance its diagnostic performance and impact on patient outcomes.

Reference –

Lin, LC., Chuan, MH., Liu, JH. et al. Proenkephalin as a biomarker correlates with acute kidney injury: a systematic review with meta-analysis and trial sequential analysis. Crit Care 27, 481 (2023). https://doi.org/10.1186/s13054-023-04747-5.