Proenkephalin as a new biomarker for pediatric acute kidney injury – reference values and performance in children under one year of age

Hartman, Stan; Zwiers, Alexandra; Water, Nadies E C van de; Rosmalen, Joost van; Struck, Joachim; Schulte, Janin; Hartmann, Oliver; Pickkers, Peter; Beunders, Remi; Tibboel, Dick; Schreuder, Michiel F.

doi:10.1515/cclm-2020-0381

Cited by 7 publications

(2 citation statements)

References 51 publications

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“…Urinary levels of kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), and the more recently discovered tissue inhibitor of metalloproteinases-2 (TIMP-2), insulinlike growth factor-binding protein 7 (IGFP7), and proenkephalin (PENK) have shown to correlate closely with degree of kidney injury in adult-intensive care patients and are available as screening panels [59]. However, for most of these novel markers of kidney function, pediatric reference intervals are still lacking or only recently being defined [60]. To date, routine use of these novel biomarkers is not (yet) implemented in many hospitals.…”

Section: Discussionmentioning

confidence: 99%

Reliability of glomerular filtration rate estimating formulas compared to iohexol plasma clearance in critically ill children

et al. 2022

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Accurate renal function assessment is crucial to guide intensive care decision-making and drug dosing. Estimates of glomerular filtration rate (eGFR) are routinely used in critically ill children; however, these formulas were never evaluated against measured GFR (mGFR) in this population. We aimed to assess the reliability of common eGFR formulas compared to iohexol plasma clearance (CL iohexol ) in a pediatric intensive care (PICU) population. Secondary outcomes were the prevalence of acute kidney injury (AKI) (by pRIFLE criteria) and augmented renal clearance (ARC) (defined as standard GFR for age + 2 standard deviations (SD)) within 48 h after admission based on mGFR and eGFR by the revised Schwartz formula and the difference between these two methods to diagnose AKI and ARC. In children, between 0 and 15 years of age, without chronic renal disease, GFR was measured by CL iohexol and estimated using 26 formulas based on creatinine (Scr), cystatine C (CysC), and betatrace protein (BTP), early after PICU admission. eGFR and mGFR results were compared for the entire study population and in subgroups according to age, using Bland-Altman analysis with calculation of bias, precision, and accuracy expressed as percentage of eGFR results within 30% (P30) and 10% (P10) of mGFR. CL iohexol was measured in 98 patients. Mean CL iohexol (± SD) was 115 ± 54 ml/min/1.73m 2 . Most eGFR formulas showed overestimation of mGFR with large bias and poor precision reflected by wide limits of agreement (LoA). Bias was larger with CysC-and BTP-based formulas compared to Scr-based formulas. In the entire study population, none of the eGFR formulas showed the minimal desired P30 > 75%. The widely used revised Schwartz formula overestimated mGFR with a high percentage bias of − 18 ± 51% (95% confidence interval (CI) − 29; − 9), poor precision with 95% LoA from − 120 to 84% and insufficient accuracy reflected by P30 of only 51% (95% CI 41; 61), and P10 of 21% (95% CI 13; 66) in the overall population. Although performance of Scr-based formulas was worst in children below 1 month of age, exclusion of neonates and younger children did not result in improved agreement and accuracy. Based on mGFR, prevalence of AKI and ARC within 48 h was 17% and 45% of patients, respectively. There was poor agreement between revised Schwartz formula and mGFR to diagnose AKI (kappa value of 0.342, p < 0.001; sensitivity of 30%, 95% CI 5; 20%) and ARC (kappa value of 0.342, p < 0.001; sensitivity of 70%, 95% CI 33; 58). Conclusion:In this proof-of-concept study, eGFR formulas were found to be largely inaccurate in the PICU population. Clinicians should therefore use these formulas with caution to guide drug dosing and therapeutic interventions in critically ill children. More research in subgroup populations is warranted to conclude on generalizability of these study findings. ClinicalTrials.gov NCT05179564, registered retrospectively on January 5, 2022. What is Known: • Both acute kidney injury and augmented renal clearance may be present in PICU patients an...

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Section: Discussionmentioning

confidence: 99%

Reliability of glomerular filtration rate estimating formulas compared to iohexol plasma clearance in critically ill children

et al. 2022

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“…Establishment of penKid reference value in healthy infants; discrimination between AKI and non-AKI children (KDIGO) (21). PenKid levels in neonates and children correlate well with iohexol GFR measurements; discriminates between AKI and non-AKI (43).…”

Section: Neonates and Childrenmentioning

confidence: 99%

Acute Kidney Injury in the Emergency Department: Role of Proenkephalin A 119-159

Crisanti,

Somma

2024

Eurasian J Emerg Med

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This condition refers to an abrupt decrease in kidney function associated with the retention of urea and other nitrogenous waste products and dysregulation of extracellular volume and electrolytes. AKI is currently defined and diagnosed using serum creatinine (sCr) and urine output (5,6), although these data provide limited and delayed information regarding changes in kidney injury and exhibit low sensitivity and specificity (7).

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Furosemide stress test to predict acute kidney injury progression in critically ill children

Krishnasamy,

Sinha,

Lodha

et al. 2024

Pediatr Nephrol

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Proenkephalin as a new biomarker for pediatric acute kidney injury – reference values and performance in children under one year of age

Cited by 7 publications

References 51 publications

Reliability of glomerular filtration rate estimating formulas compared to iohexol plasma clearance in critically ill children

Reliability of glomerular filtration rate estimating formulas compared to iohexol plasma clearance in critically ill children

Acute Kidney Injury in the Emergency Department: Role of Proenkephalin A 119-159

Furosemide stress test to predict acute kidney injury progression in critically ill children

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