Dataset Information

Proteomic identification of early urinary-biomarkers of acute kidney injury in preterm infants.

ABSTRACT: The immature preterm kidney is likely to be vulnerable to acute kidney injury (AKI). However, the biomarkers currently used for AKI are not sensitive or specific and are also inadequate for the timely detection of AKI in preterm infants. The objectives of this study were to identify novel urinary biomarkers of AKI using proteomic techniques, and to verify and validate that the candidates can serve as early predictive biomarkers for AKI. In total, 1,810 proteins were identified in the discovery phase. Among those proteins, 174 were selected as the 1st targeted proteins. A total of 168 proteins were quantified, and the levels of 6 were significantly increased in the AKI group in the verification phase. Using a clinical assay, the results were confirmed and validated using samples of the first urine after birth from the biorepository. Finally, enzyme-linked immunosorbent assays revealed that the levels of annexin A5, neutrophil gelatinase-associated lipocalin (NGAL), and protein S100-P were significantly higher in the samples of the first urine from patients with AKI than in those from patients without AKI. In conclusion, urinary annexin A5, NGAL and protein S100-P levels are promising biomarkers for early, accurate prediction of AKI in preterm infants.

SUBMITTER: Jung YH

PROVIDER: S-EPMC7055268 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Proteomic identification of early urinary-biomarkers of acute kidney injury in preterm infants.

Jung Young Hwa YH Han Dohyun D Shin Seung Han SH Kim Ee-Kyung EK Kim Han-Suk HS

Scientific reports 20200304 1

The immature preterm kidney is likely to be vulnerable to acute kidney injury (AKI). However, the biomarkers currently used for AKI are not sensitive or specific and are also inadequate for the timely detection of AKI in preterm infants. The objectives of this study were to identify novel urinary biomarkers of AKI using proteomic techniques, and to verify and validate that the candidates can serve as early predictive biomarkers for AKI. In total, 1,810 proteins were identified in the discovery p ...[more]

PMID: 32132597

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Project description:BackgroundSerum creatinine is a delayed marker of acute kidney injury (AKI). Our purpose is to discover and validate novel early urinary biomarkers of AKI after cardiac surgery.Study designDiagnostic test study.Setting & participantsChildren undergoing cardiopulmonary bypass surgery. The test set included 15 participants with AKI and 15 matched controls (median age, 1.5 year) of 45 participants without AKI. The validation set included 365 children (median age, 1.9 year).Index testsBiomarkers identified using proteomic profiling: α(1)-microglobulin, α(1)-acid glycoprotein, and albumin.Reference testAKI, defined as ≥50% increase in serum creatinine level from baseline within 3 days of surgery.ResultsProteomic profiling using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) showed 3 protein peaks that appeared consistently within 2 hours in children who developed AKI after cardiopulmonary bypass surgery. The proteins were identified as α(1)-microglobulin, α(1)-acid glycoprotein, and albumin. Using clinical assays, results were confirmed in a test set and validated in an independent prospective cohort. In the validation set, 135 (37%) developed AKI, in whom there was a progressive increase in urinary biomarker concentrations with severity of AKI. Areas under the curve for urinary α(1)-microglobulin, α(1)-acid glycoprotein, and albumin at 6 hours after cardiac surgery were 0.84 (95% CI, 0.79-0.89), 0.87 (95% CI, 0.83-0.91), and 0.76 (95% CI, 0.71-0.81), respectively. Participants with increasing quartiles of biomarkers showed increasing lengths of hospital stays and durations of AKI (P < 0.001).LimitationsSingle-center study of children with normal kidney function at recruitment. The SELDI-TOF MS technique has limited sensitivity for the detection of proteins greater than the 20-kDa range.ConclusionsUrinary α(1)-microglobulin, α(1)-acid glycoprotein, and albumin represent early, accurate, inexpensive, and widely available biomarkers of AKI after cardiac surgery. They also offer prognostic information about the duration of AKI and length of hospitalization after cardiac surgery.

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:BackgroundHump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1-10%) following HNV envenoming. We aimed to identify the value of functional and injury biomarkers in predicting the development of AKI early following HNV bites.MethodsWe conducted a prospective cohort study of patients with confirmed HNV envenoming presenting to two large tertiary care hospitals in Sri Lanka. Demographics, bite details, clinical effects, complications and treatment data were collected prospectively. Blood and urine samples were collected from patients for coagulation and renal biomarker assays on admission, at 0-4h, 4-8h, 8-16h and 16-24h post-bite and daily until discharge. Follow-up samples were obtained 1 and 3 months post-discharge. Creatinine (sCr) and Cystatin C (sCysC) were measured in serum and kidney injury molecule-1 (uKIM-1), clusterin (uClu), albumin (uAlb), β2-microglobulin (uβ2M), cystatin C (uCysC), neutrophil gelatinase associated lipocalin (uNGAL), osteopontin (uOPN) and trefoil factor-3 (uTFF-3) were measured in urine. Definite HNV bites were based on serum venom specific enzyme immunoassay. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to stage AKI. Two patients had chronic kidney disease at 3 month follow-up, both with pre-existing abnormal sCr, and one developed AKI following HNV envenoming.ResultsThere were 52 patients with confirmed HNV envenoming; median age 48y (Interquartile range [IQR]:40-59y) and 29 (56%) were male. Median time to admission was 1.87h (IQR:1-2.75h). Twelve patients (23%) developed AKI (AKI stage 1 = 7, AKI stage 2 = 1, AKI stage 3 = 4). Levels of five novel biomarkers, the functional marker serum Cystatin C and the damage markers urinary NGAL, cystatin C, β2-microglobulin and clusterin, were elevated in patients who developed moderate/severe acute kidney injury. sCysC performed the best at 0-4 h post-bite in predicting moderate to severe AKI (AUC-ROC 0.95;95%CI:0.85-1.0) and no biomarker performed better than sCr at later time points.ConclusionssCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following HNV envenoming.

Project description:Background: Acute kidney injury (AKI) is a common cause of organ failure in trauma patients who survive their initial injuries. It is independently associated with increased morbidity and mortality and prolongs the length of hospital stays. The objectives of this study were to describe the incidence of early AKI and influence of risk factors in polytrauma patients and evaluate the predictive potential of TIMP2 × IGFBP7 biomarkers in this patient cohort. Methods: We conducted a retrospective cohort study of severely injured adult patients who were consecutively admitted to a multidisciplinary ICU from May 2017 to May 2019. Detailed patient data was retrieved from ICU medical records. Fluid balance, urinary output, and sCr values up to 72 h were collected. Urine samples for measuring TIMP2 × IGFBP7 concentrations were obtained and analyzed from ICU admission to 72 h. Results: Among the 153 patients eligible for analysis, 45 were included in the AKI, and 108 in the no AKI cohorts. The incidence of AKI within 72 h, based on KDIGO criteria, was 28.8%. There were no differences in ISS, type and mechanism of injury, heart rate, and systolic BP at admission between groups. Patients with early AKI were older (68 vs. 49 years, p < 0.001), obese (BMI 26.2 vs. 24.7, p < 0.048), and more likely to have previous cardiac disease (27% vs. 5.6%, p < 0.001). TIMP2 × IGFBP7 values on ICU admission were associated with subsequent AKI in patients without evidence of AKI at the time of ICU admission. They were also higher in the AKI cohort and significantly correlated with renal replacement therapy (RRT) and episodes of hypotension. Multivariable analysis confirmed age, previous cardiac disease, and NephroCheck as the variables mostly associated with AKI, with AUC 0.792. Conclusions: TIMP2 × IGFBP7 may help identify trauma patients with tubular damage that may evolve into a clinically manifested syndrome. Prospective studies of TIMP2 × IGFBP7, as a trigger for early AKI bundle care, are warranted.

Dataset Information

Proteomic identification of early urinary-biomarkers of acute kidney injury in preterm infants.

Publications

Proteomic identification of early urinary-biomarkers of acute kidney injury in preterm infants.

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