• Toxicological Research
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• 제32권1호
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• pp.47-56
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• 2016

The identification of biomarkers for the early detection of acute kidney injury (AKI) is clinically important. Acute kidney injury (AKI) in critically ill patients is closely associated with increased morbidity and mortality. Conventional biomarkers, such as serum creatinine (SCr) and blood urea nitrogen (BUN), are frequently used to diagnose AKI. However, these biomarkers increase only after significant structural damage has occurred. Recent efforts have focused on identification and validation of new noninvasive biomarkers for the early detection of AKI, prior to extensive structural damage. Furthermore, AKI biomarkers can provide valuable insight into the molecular mechanisms of this complex and heterogeneous disease. Our previous study suggested that pyruvate kinase M2 (PKM2), which is excreted in the urine, is a sensitive biomarker for nephrotoxicity. To appropriately and optimally utilize PKM2 as a biomarker for AKI requires its complete characterization. This review highlights the major studies that have addressed the diagnostic and prognostic predictive power of biomarkers for AKI and assesses the potential usage of PKM2 as an early biomarker for AKI. We summarize the current state of knowledge regarding the role of biomarkers and the molecular and cellular mechanisms of AKI. This review will elucidate the biological basis of specific biomarkers that will contribute to improving the early detection and diagnosis of AKI.

• Childhood Kidney Diseases
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• 제15권2호
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• pp.116-124
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• 2011

Acute kidney injury (AKI) can result in mortality or progress to chronic kidney disease in hospitalized patients. Although serum creatinine has long been used as the best biomarker for diagnosis of AKI, it has some clinical limitations, especially in children. New biomarkers are needed for early diagnosis, differential diagnosis, and reliable prediction of prognosis in AKI. Up to the present, candidate AKI biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), livertype fatty acid-binding protein (L-FABP), matrix metalloproteinase-9 (MMP-9), and Nacetyl-$\ss$-D-glucosaminidase (NAG). However, whether these are superior to serum creatinine in the confirmation of diagnosis and prediction of prognosis in AKI is unclear. Further studies are needed for clinical application of these new biomarkers in AKI.

• 대한임상검사과학회지
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• 제48권2호
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• pp.49-53
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• 2016

급성 심 질환 환자는 트로포닌(troponin)과 같은 생물학적 표지자(biomarker)가 등장하면서 진단과 치료에 많은 개선이 있었다. 콩팥 질환에서는 많은 치료약제 개발이 꾸준하게 진전해 왔음에도 불구하고 실제 사망률이나 이환률은 별로 개선되지 않았다. 급성 콩팥 손상 환자를 대상으로 응급의료센터에서 측정한 NGAL의 측정치는 NGAL이 증가할수록 Creatinine이 유의하게 증가 하였다. 그러나, AST, ALT, BUN, Na, K, Cl 과의 상관관계는 통계적으로 유의하지 않았다. NAGL kit와 ELISA의 민감도는 ${\geq}300$ (92.2%), ${\geq}200$ (95.6%), ${\geq}100$ (99.6%), 특이도는 ${\geq}300$ (95.1%), ${\geq}200$ (97.3%), ${\geq}100$ (99.4%)로 조사되었으며 양성예측도는 ${\geq}300$ (93.3%), ${\geq}200$ (93.4%), ${\geq}100$ (99.2%), 음성예측도는 ${\geq}300$ (96.7%), ${\geq}200$ (97.7%), ${\geq}100$ (98.1%)로 조사되었으며, 급성 콩팥 손상의 정도를 평가하는 검사로써 조기 진단 및 예후를 예측함에 있어서 환자의 치료의 결정에 유용하게 이용 될 수 있다. 향후 응급의료센터에서 콩팥 질환 환자의 중증도를 평가하고 치료 방향을 결정하며, 예후를 예측하는데 있어서 NGAL kit 검사가 도움이 될 수 있다고 생각한다.

• Childhood Kidney Diseases
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• 제19권2호
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• pp.71-78
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• 2015

The incidence of acute kidney injury (AKI) in critically ill pediatric patients has been reported as increasing to 25 %, depending on population characteristics. The etiology of AKI has changed over the last 10-20 years from primary renal disease to the renal conditions associated with systemic illness. The AKI in pediatric population is associated with increased mortality and morbidity, and prevention is needed to reduce the consequence of AKI. It is known that the most important risk factors for AKI in critically ill pediatric patients are clinical conditions to be associated with decreased renal blood flow, direct renal injury, and illness severity. Renal hypoperfusion leads to neurohormonal activation including renin-angiotensin-aldosterone system, sympathetic nervous system, antidiuretic hormone, and prostaglandins. Prolonged renal hypoperfusion can result in acute tubular necrosis. The direct renal injury can be predisposed under the condition of renal hypoperfusion, and appropriate treatment of volume depletion is important to prevent AKI. The preventable causes of AKI include contrast-induced nephropathy, hemodynamic instability, inappropriate mediation use, and multiple nephrotoxic insults. Given the evidence of preventable factors for AKI, several actions such as the use of protocol for prevention of contrast-induced nephropathy, appropriate treatment of volume depletion, vigorous treatment of sepsis, avoidance of combinations of nephrotoxic medications, and monitoring of levels of drugs should be recommended.

• Clinical and Experimental Pediatrics
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• 제63권4호
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• pp.151-156
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• 2020

Background: Acute kidney injury (AKI) is one of the most significant postoperative complications of pediatric cardiac surgery. Because serum creatinine has limitations as a diagnostic marker of AKI, new biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) are being evaluated to overcome these limitations and detect AKI at an early stage after cardiac surgery. Purpose: This study aimed to investigate the clinical usefulness of these biomarkers in young children. Methods: Thirty patients with congenital heart diseases who underwent cardiac surgery using cardiopulmonary bypass (CPB) were selected, and their urine and blood samples were collected at baseline and 6, 24, and 48 hours after surgery. Serum creatinine and blood urea nitrogen levels as well as NGAL, KIM-1, and IL-18 levels in urine samples were measured, and clinical parameters were evaluated. Results: Of the 30 patients, 12 developed AKI within 48 hours after cardiac surgery. In the AKI group, 8 of 12 (66.6%) met AKI criteria after 24 hours, and urine KIM-1/creatinine (Cr) level (with adjustment of urine creatinine) peaked at 24 hours with significant difference from baseline level. Additionally, urine KIM-1/Cr level in the AKI group was significantly higher than in the non-AKI group at 6 hours. However, urine NGAL/Cr and IL-18/Cr levels showed no specific trend with time for 48 hours after cardiac surgery. Conclusion: It is suggested that urine KIM-1/Cr concentration could be considered a good biomarker for early AKI prediction after open cardiac surgery using CPB in young children with congenital heart diseases.

• Journal of Chest Surgery
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• 제47권3호
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• pp.240-248
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• 2014

Background: Open heart surgery using cardiopulmonary bypass (CPB) is considered one of the most frequent surgical procedures in which acute kidney injury (AKI) is a frequent and serious complication. The aim of the present study was to evaluate the efficiency of neutrophil gelatinase-associated lipocalin (NGAL) as an early AKI biomarker after CPB in cardiac surgery (CS). Methods: Thirty-seven adult patients undergoing CS with CPB were included in this retrospective study. They had normal preoperative renal function, as assessed by the creatinine (Cr) level, NGAL level, and estimated glomerular filtration rate. Serial evaluation of serum NGAL and Cr levels was performed before, immediately after, and 24 hours after the operation. Patients were divided into two groups: those who showed normal immediate postoperative serum NGAL levels (group A, n=30) and those who showed elevated immediate postoperative serum NGAL levels (group B, n=7). Statistical analysis was performed using Statistical Package for the Social Sciences version 18. Results: Of the 37 patients, 6 (6/37, 16.2%) were diagnosed with AKI. One patient belonged to group A (1/30, 3.3%), and 5 patients belonged to group B (5/7, 71.4%). Two patients in group B (2/7, 28.5%) required further renal replacement therapy. Death occurred in only 1 patient (1/37, 2.7%), who belonged to group B. Conclusion: The results of this study suggest that postoperative plasma NGAL levels can be used as an early biomarker for the detection of AKI following CS using CPB. Further studies with a larger sample size are needed to confirm our results.

• Kidney Research and Clinical Practice
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• 제37권4호
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• pp.338-346
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• 2018

Background: The most common cause of acute kidney injury (AKI) in pregnancy is preeclampsia. Serum cystatin C (CysC) is a potential biomarker of early kidney damage as its levels are not disturbed by volume status changes in pregnancy, and serum CysC levels could serve as a replacement for conventionally used creatinine. In this study, we investigated the serum levels of CysC in severe preeclampsia cases and the associations between CysC levels and poor obstetric outcomes. Methods: Our cohort included severe preeclampsia patients with a normal serum creatinine level. Creatinine was measured to calculate estimated glomerular filtration rate (eGFR) based on the Cockcroft and Gault, Modification of Diet in Renal Disease Study (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, while CysC was measured to calculated eGFR based on a CysC-based equation. We then evaluated the correlations between serum CysC level, eGFR, and obstetric outcomes. Results: Twenty-six patients were evaluated of which 38.5% delivered preterm and 30.8% had low-birth weight babies. Unlike creatinine-based eGFR and CysC-based eGFR, serum CysC demonstrate significant negative correlation with gestational age. Receiver operating characteristic curve analysis indicated that serum CysC is a potential biomarker of preterm delivery with a cut-off serum level of 1.48 mg/L with 80% sensitivity and 75% specificity. Conclusion: GFR estimation using CysC is likely to be inaccurate in pregnancy. However, we found a significant correlation between preterm delivery and serum CysC level. Our results suggest that serum CysC level has the potential to predict preterm delivery in severe preeclampsia patients.