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Urine biomarkers for monitoring acute kidney injury in premature infants.

ABSTRACT: Background:Premature infants are at high risk for acute kidney injury (AKI). Serum creatinine (Cr) has limitations for evaluating kidney function in premature infants. We evaluated whether urine biomarkers could be used to monitor AKI in premature infants. Methods:A prospective cohort study was conducted among infants born at < 37 weeks. Urine biomarkers and serum Cr were measured on postnatal days 1, 3, 5, 7, 10, and 14. Infants were divided into 3 groups according to gestational age (GA); < 28, 28 to < 32 and 32 to < 37 weeks. Results:AKI occurred in 17 of 83 (20.5%) recruited infants at a median age of 7 (interquartile range 5-10) days. While the most common cause of AKI was hemodynamically significant patent ductus arteriosus (53.8%) in infants of GA < 28 weeks, necrotizing enterocolitis was the leading cause (50.0%) in infants of GA 28 to < 32 weeks. Urinary levels of neutrophil-gelatinase-associated lipocalin/Cr were higher and epidermal growth factor/Cr were lower in AKI group before the onset of AKI in infants of GA < 28 weeks. In infants of GA 28 to < 32 weeks, urinary interleukin-8/Cr levels were higher in AKI group at approximately the time of AKI onset. Conclusion:Several urine biomarkers were significantly different between AKI and no AKI groups, and some had changed before the onset of AKI. These groups were distinct according to causative factors of AKI and GA. Urine biomarkers could be useful for monitoring the development of AKI in premature infants.

SUBMITTER: Ahn YH

PROVIDER: S-EPMC7530367 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Urine biomarkers for monitoring acute kidney injury in premature infants.

Ahn Yo Han YH Lee Juyoung J Chun Jiyoung J Jun Yong Hoon YH Sung Tae-Jung TJ

Kidney research and clinical practice 20200901 3

<h4>Background</h4>Premature infants are at high risk for acute kidney injury (AKI). Serum creatinine (Cr) has limitations for evaluating kidney function in premature infants. We evaluated whether urine biomarkers could be used to monitor AKI in premature infants.<h4>Methods</h4>A prospective cohort study was conducted among infants born at < 37 weeks. Urine biomarkers and serum Cr were measured on postnatal days 1, 3, 5, 7, 10, and 14. Infants were divided into 3 groups according to gestational ...[more]

PMID: 32839353

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Project description:Background and objectivesThe current threshold used for oliguria in the definition of neonatal AKI has been empirically defined as 1 ml/kg per hour. Urine output criteria are generally poorly documented, resulting in uncertainty in the most accurate threshold to identify AKI in very preterm infants with known tubular immaturity.Design, setting, participants, & measurementsWe conducted a bicentric study including 473 very preterm infants (240/7-296/7 weeks of gestation) born between January 2014 and December 2018 with urine output measurements every 3 hours during the first 7 days of life and two serum creatinine measurements during the first 10 days of life. AKI was defined using the neonatal Kidney Disease Improving Global Outcomes (KDIGO) definition. We tested whether higher urine output thresholds (1.5 or 2 ml/kg per hour) in modified AKI definitions may better discriminate neonatal mortality compared with the current definition.ResultsEarly-onset AKI was developed by 101 of 473 (21%) very preterm infants. AKI was diagnosed on the basis of urine output criteria alone (no rise in creatinine) for 27 of 101 (27%) participants. Early-onset AKI was associated with higher risk of death before discharge (adjusted odds ratio, 3.9; 95% confidence interval, 1.9 to 7.8), and the AKI neonatal KDIGO score showed good discriminative performance for neonatal mortality, with an area under the receiver operating characteristic (ROC) curve of 0.68 (95% confidence interval, 0.61 to 0.75). Modified AKI definitions that included higher urine output thresholds showed significantly improved discriminative performance, with areas under the ROC curve of 0.73 (95% confidence interval, 0.66 to 0.80) for the 1.5-ml/kg per hour threshold and 0.75 (95% confidence interval, 0.68 to 0.81) for the 2-ml/kg per hour threshold.ConclusionsEarly-onset AKI was diagnosed on the basis of urine output exclusively for a quarter of the cases. Furthermore, modified AKI definitions that included higher urine output improved the discriminative performance for predicting mortality.

Project description:BackgroundThe study of novel urinary biomarkers of acute kidney injury has expanded exponentially. Effective interpretation of data and meaningful comparisons between studies require awareness of factors that can adversely affect measurement. We examined how variations in short-term storage and processing might affect the measurement of urine biomarkers.Study designCross-sectional prospective.Setting & participantsHospitalized patients from 2 sites: Yale New Haven Hospital (n=50) and University of California, San Francisco Medical Center (n=36).PredictorsWe tested the impact of 3 urine processing conditions on these biomarkers: (1) centrifugation and storage at 4°C for 48 hours before freezing at -80°C, (2) centrifugation and storage at 25°C for 48 hours before freezing at -80°C, and (3) uncentrifuged samples immediately frozen at -80°C.OutcomesUrine concentrations of 5 biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), and cystatin C.MeasurementsWe measured urine biomarkers by established enzyme-linked immunosorbent assay methods. Biomarker values were log-transformed, and agreement with a reference standard of immediate centrifugation and storage at -80°C was compared using concordance correlation coefficients (CCCs).ResultsNeither storing samples at 4°C for 48 hours nor centrifugation had a significant effect on measured levels, with CCCs higher than 0.9 for all biomarkers tested. For samples stored at 25°C for 48 hours, excellent CCC values (>0.9) also were noted between the test sample and the reference standard for NGAL, cystatin C, L-FABP and KIM-1. However, the CCC for IL-18 between samples stored at 25°C for 48 hours and the reference standard was 0.81 (95% CI, 0.66-0.96).LimitationsNo comparisons to fresh, unfrozen samples; no evaluation of the effect of protease inhibitors.ConclusionsAll candidate markers tested using the specified assays showed high stability with both short-term storage at 4°C and without centrifugation prior to freezing. For optimal fidelity, urine for IL-18 measurement should not be stored at 25°C before long-term storage or analysis.

Project description:The interaction between baseline kidney function and the performance of biomarkers of acute kidney injury (AKI) on the development of AKI is unclear.Post hoc analysis of prospective cohort study.The 1,219 TRIBE-AKI Consortium adult cardiac surgery cohort participants.Unadjusted postoperative urinary biomarkers of AKI measured within 6 hours of surgery.AKI was defined as AKI Network stage 1 (any AKI) or higher, as well as a doubling of serum creatinine level from the preoperative value or the need for post-operative dialysis (severe AKI).Stratified analyses by preoperative estimated glomerular filtration rate (eGFR) ? 60 versus > 60mL/min/1.73m(2).180 (42%) patients with preoperative eGFRs?60mL/min/1.73m(2) developed clinical AKI compared with 246 (31%) of those with eGFRs>60mL/min/1.73m(2) (P<0.001). For log2-transformed biomarker concentrations, there was a significant interaction between any AKI and baseline eGFR for interleukin 18 (P=0.007) and borderline significance for liver-type fatty acid binding protein (P=0.06). For all biomarkers, the adjusted relative risk (RR) point estimates for the risk for any AKI were higher in those with elevated baseline eGFRs compared with those with eGFRs?60mL/min/1.73m(2). However, the difference in magnitude of these risks was low (adjusted RRs were 1.04 [95% CI, 0.99-1.09] and 1.11 [95% CI, 1.07-1.15] for those with preoperative eGFRs?60mL/min/1.73m(2) and those with higher eGFRs, respectively). Although no biomarker displayed an interaction for baseline eGFR and severe AKI, log2-transformed interleukin 18 and kidney injury molecule 1 had significant adjusted RRs for severe AKI in those with and without baseline eGFRs?60mL/min/1.73m(2).Limited numbers of patients with severe AKI and post-operative dialysis.The association between early postoperative AKI urinary biomarkers and AKI is modified by preoperative eGFR. The degree of this modification and its impact on the biomarker-AKI association is small across biomarkers. Our findings suggest that distinct biomarker cutoffs for those with and without a preoperative eGFR?60mL/min/1.73m(2) is not necessary.

Project description:BackgroundAcute kidney injury (AKI) is a common complication of cardiac surgery. An intraoperative monitor of kidney perfusion is needed to identify patients at risk for AKI. The authors created a noninvasive urinary oximeter that provides continuous measurements of urinary oxygen partial pressure and instantaneous urine flow. They hypothesized that intraoperative urinary oxygen partial pressure measurements are feasible with this prototype device and that low urinary oxygen partial pressure during cardiac surgery is associated with the subsequent development of AKI.MethodsThis was a prospective observational pilot study. Continuous urinary oxygen partial pressure and instantaneous urine flow were measured in 91 patients undergoing cardiac surgery using a novel device placed between the urinary catheter and collecting bag. Data were collected throughout the surgery and for 24 h postoperatively. Clinicians were blinded to the intraoperative urinary oxygen partial pressure and instantaneous flow data. Patients were then followed postoperatively, and the incidence of AKI was compared to urinary oxygen partial pressure measurements.ResultsIntraoperative urinary oxygen partial pressure measurements were feasible in 86/91 (95%) of patients. When urinary oxygen partial pressure data were filtered for valid urine flows greater than 0.5 ml · kg-1 · h-1, then 70/86 (81%) and 77/86 (90%) of patients in the cardiopulmonary bypass (CPB) and post-CPB periods, respectively, were included in the analysis. Mean urinary oxygen partial pressure in the post-CPB period was significantly lower in patients who subsequently developed AKI than in those who did not (mean difference, 6 mmHg; 95% CI, 0 to 11; P = 0.038). In a multivariable analysis, mean urinary oxygen partial pressure during the post-CPB period remained an independent risk factor for AKI (relative risk, 0.82; 95% CI, 0.71 to 0.95; P = 0.009 for every 10-mmHg increase in mean urinary oxygen partial pressure).ConclusionsLow urinary oxygen partial pressures after CPB may be associated with the subsequent development of AKI after cardiac surgery.Editor’s perspective

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Urine biomarkers for monitoring acute kidney injury in premature infants.

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Urine biomarkers for monitoring acute kidney injury in premature infants.

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