Proenkephalin: A New Biomarker for Glomerular Filtration Rate and Acute Kidney Injury

Khorashadi, Mina; Beunders, Remi; Pickkers, Peter; Legrand, Matthieu

doi:10.1159/000509352

Cited by 54 publications

(21 citation statements)

References 31 publications

(54 reference statements)

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“…Enkephalins are endogenous opioids that are widely expressed and act primarily on δ-opioid receptors, which are primarily expressed in the central nervous system and the kidney. It has been suggested that enkephalins have a regulatory role in kidney function, such as inducing diuresis and natriuresis [19]. Although elevated cDPP3 was associated with all types of organ dysfunction, the correlation network analysis (Fig.…”

Section: Deniau Et Al Investigated the Association Of Cdpp3 Levels And Mortality In Cardiogenic Shock Patients Andmentioning

confidence: 96%

Circulating dipeptidyl peptidase 3 on intensive care unit admission is a predictor of organ dysfunction and mortality

et al. 2021

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Background Our aim was to investigate the prognostic potential of circulating dipeptidyl peptidase 3 (cDPP3) to predict mortality and development of organ dysfunction in a mixed intensive care unit (ICU) population, and for this reason, we analysed prospectively collected admission blood samples from adult ICU patients at four Swedish hospitals. Blood samples were stored in a biobank for later batch analysis. The association of cDPP3 levels with 30-day mortality and Sequential Organ Failure Assessment (SOFA) scores on day two was investigated before and after adjustment for the simplified acute physiology score III (SAPS-3), using multivariable (ordinal) logistic regression. The predictive power of cDPP3 was assessed using the area under the receiver operating characteristic curve (AUROC). Results Of 1978 included consecutive patients in 1 year (2016), 632 fulfilled the sepsis 3-criteria, 190 were admitted after cardiac arrest, and 157 because of trauma. Admission cDPP3 was independently (of SAPS-3) associated with 30-day mortality with odds ratios of 1.45 (95% confidence interval (CI) 1.28–1.64) in the entire ICU population, 1.30 (95% CI 1.08–1.57) in the sepsis subgroup and 2.28 (95% CI 1.50–3.62) in cardiac arrest. For trauma, there was no clear association. Circulating DPP3 alone was a moderate predictor of 30-day mortality with AUROCs of 0.68, 0.62, and 0.72 in the entire group, the sepsis subgroup, and the cardiac arrest subgroup, respectively. By adding cDPP3 to SAPS-3, AUROC improved for the entire group, the sepsis subgroup, and the cardiac arrest subgroup (p = 0.023). Conclusion Circulating DPP3 on admission is a SAPS-3 independent prognostic factor of day-two organ dysfunction and 30-day mortality in a mixed ICU population and needs further evaluation.

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Section: Deniau Et Al Investigated the Association Of Cdpp3 Levels And Mortality In Cardiogenic Shock Patients Andmentioning

confidence: 96%

Circulating dipeptidyl peptidase 3 on intensive care unit admission is a predictor of organ dysfunction and mortality

et al. 2021

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“…The association between PENK concentrations and renal dysfunction might be explained by compensatory increased PENK production to exert kidney protective effects, 2 or alternatively reflect impaired clearance since PENK is likely to be freely filtered through the glomerulus due to its low molecular weight (4586.60 g/mol) and is not known to have a binding protein 5 . PENK has therefore also been suggested as a reflector of glomerular function especially in the acute setting 5,28 . Whatever the underlying mechanisms are, PENK concentrations have previously been associated with decline of eGFR and incident CKD in the general population, 6 although in a previous study conducted in PREVEND this association was only found in men 7 .…”

Section: Discussionmentioning

confidence: 99%

“… 5 PENK has therefore also been suggested as a reflector of glomerular function especially in the acute setting. 5 , 28 Whatever the underlying mechanisms are, PENK concentrations have previously been associated with decline of eGFR and incident CKD in the general population, 6 although in a previous study conducted in PREVEND this association was only found in men. 7 The heart and the kidney are closely intertwined where failure of one can lead to failure of the other, 29 which makes the relationship of PENK with renal dysfunction and CKD interesting to investigate with regards to new‐onset HF.…”

Section: Discussionmentioning

confidence: 99%

Proenkephalin and the risk of new‐onset heart failure: data from prevention of renal and vascular end‐stage disease

Emmens

Maaten

Brouwers

et al. 2021

Clinical Cardiology

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Background Enkephalins of the opioid system exert several cardiorenal effects. Proenkephalin (PENK), a stable surrogate, is associated with heart failure (HF) development after myocardial infarction and worse cardiorenal function and prognosis in patients with HF. The association between plasma PENK concentrations and new‐onset HF in the general population remains to be established. Hypothesis We hypothesized that plasma PENK concentrations are associated with new‐onset HF in the general population. Methods We included 6677 participants from the prevention of renal and vascular end‐stage disease study and investigated determinants of PENK concentrations and their association with new‐onset HF (both reduced [HFrEF] and preserved ejection fraction [HFpEF]). Results Median PENK concentrations were 52.7 (45.1–61.9) pmol/L. Higher PENK concentrations were associated with poorer renal function and higher NT‐proBNP concentrations. The main determinants of higher PENK concentrations were lower estimated glomerular filtration rate (eGFR), lower urinary creatinine excretion, and lower body mass index (all p < .001). After a median 8.3 (7.8–8.8) years follow‐up, 221 participants developed HF; 127 HFrEF and 94 HFpEF. PENK concentrations were higher in subjects who developed HF compared with those who did not, 56.2 (45.2–67.6) versus 52.7 (45.1–61.6) pmol/L, respectively (p = .003). In competing‐risk analyses, higher PENK concentrations were associated with higher risk of new‐onset HF (hazard ratio [HR] = 2.09[1.47–2.97], p < .001), including both HFrEF (HR = 2.31[1.48–3.61], p < .001) and HFpEF (HR = 1.74[1.02–2.96], p = .042). These associations were, however, lost after adjustment for eGFR. Conclusions In the general population, higher PENK concentrations were associated with lower eGFR and higher NT‐proBNP concentrations. Higher PENK concentrations were not independently associated with new‐onset HFrEF and HFpEF and mainly confounded by eGFR.

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“…Plasma levels of proenkephalin (PENKid) correlate with GFR and are more sensitive than SCr to detect AKI in critically ill patients [50,51].…”

Section: Alternative Estimates Of Gfrmentioning

confidence: 99%

Reflections on the KDIGO Definition of Acute Kidney Injury and Its Integration in the Concept of Acute Diseases and Disorders and Chronic Kidney Diseases

Lameire

2022

Kidney and Dialysis

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Acute kidney injury (AKI) describes a heterogeneous group of conditions, without specification of their etiology and diagnosed only by indirect markers of glomerular filtration rate (GFR), such as serum creatinine and urine output. Bedside estimation of GFR and detection of structural alterations with novel biomarkers, and stress tests have more recently been developed. These novel findings should probably be included in future AKI definitions. Chronic kidney disease (CKD) is defined by abnormalities in kidney function and structure that persist over >3 months and is classified according to cause, GFR, and albuminuria. Acute kidney disease (AKD) is the term representing patients with abnormalities of function and structure with a duration of ≤3 months that fall outside the definitions of AKI or CKD. Since AKI is by definition also AKD, 2 types of AKD have been proposed, one with and one without AKI. AKD without AKI is common, often undetected, occurs frequently in the outpatient population and shows increased risk of CKD, ESKD and mortality. Alternatively, AKD has also been defined as the period of incomplete recovery following an AKI episode, the latter limited for the duration of 7 days. This contribution discusses the pros and cons of the existence of these 2 definitions of AKD.

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Proenkephalin: A New Biomarker for Glomerular Filtration Rate and Acute Kidney Injury

Cited by 54 publications

References 31 publications

Circulating dipeptidyl peptidase 3 on intensive care unit admission is a predictor of organ dysfunction and mortality

Circulating dipeptidyl peptidase 3 on intensive care unit admission is a predictor of organ dysfunction and mortality

Proenkephalin and the risk of new‐onset heart failure: data from prevention of renal and vascular end‐stage disease

Reflections on the KDIGO Definition of Acute Kidney Injury and Its Integration in the Concept of Acute Diseases and Disorders and Chronic Kidney Diseases

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