scholarly journals Current understanding and future directions in the application of TIMP-2 and IGFBP7 in AKI clinical practice

2019 ◽  
Vol 57 (5) ◽  
pp. 567-576 ◽  
Author(s):  
Weixuan Fan ◽  
Ghada Ankawi ◽  
Jingxiao Zhang ◽  
Kumar Digvijay ◽  
Davide Giavarina ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Binding Protein ◽  
Kidney Injury ◽  
Clinical Work ◽  
The United States ◽  
Future Directions ◽  
Fatty Acid Binding ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Kidney Injury Molecule 1

Abstract NephroCheck® is the commercial name of a combined product of two urinary biomarkers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), expressed as [TIMP-2]·[IGFBP7], used to identify patients at high risk of acute kidney injury (AKI). AKI is a common and harmful complication especially in critically-ill patients, which can induce devastating short- and long-term outcomes. Over the past decade, numerous clinical studies have evaluated the utility of several biomarkers (e.g. neutrophil gelatinase-associated lipocalin, interleukin-18, liver-type fatty acid binding protein and kidney injury molecule-1, cystatin C) in the early diagnosis and risk stratification of AKI. Among all these biomarkers, [TIMP-2]·[IGFBP7] was confirmed to be superior in early detection of AKI, before the decrease of renal function is evident. In 2014, the US Food and Drug Administration permitted marketing of NephroCheck® (Astute Medical) (measuring urinary [TIMP-2]·[IGFBP7]) to determine if certain critically-ill patients are at risk of developing moderate to severe AKI. It has since been applied to clinical work in many hospitals of the United States and Europe to improve the diagnostic accuracy and outcomes of AKI patients. Now, more and more research is devoted to the evaluation of its application value, meaning and method in different clinical settings. In this review, we summarize the current research status of [TIMP-2]·[IGFBP7] and point out its future directions.

scholarly journals Acute Kidney Injury in Critically Ill Patients

2021 ◽  
Vol 3 (1) ◽  
pp. 8
Author(s):  
Yuswanto Setyawan
Keyword(s):  
Acute Kidney Injury ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Kidney Injury ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Kidney Injury Molecule 1 ◽  
Neutrophil Gelatinase ◽  
Urinary Cystatin C

Abstrak: Gagal ginjal akut (GGA) sering ditemukan dalam praktek klinik namun diagnosisnya dapat tertunda oleh karena keterbatasan alat diagnostik. Dewasa ini, kriteria diagnostik RIFLE, AKIN, dan KDIGO untuk menilai adanya GGA dan keparahannya dianggap tidak cukup untuk menggambarkan kompleksitas sindrom GGA. Proteinuria dan mikroalbuminuria yang merupa-kan marker klasik progresi cedera ginjal kronik, telah dipergunakan dan divalidasi untuk progresi GGA ke CKD. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), dan urinary cystatin C dapat berperan dalam memrediksi pemulihan ginjal. Indikasi biopsi ginjal pada pasien kritis ialah gangguan ginjal yang tidak jelas atau progresi CKD dengan hematuria glomerulus dan proteinuria lebih dari 1 gram per hari, manifestasi ginjal dari penyakit sistemik yang mengancam nyawa, kecurigaan penolakan akut atau kronik dari ginjal transplan. Mempertahankan hemodinamik yang adekuat seharusnya bermanfaat dalam pence-gahan onset atau perburukan GGA, namun kelebihan cairan harus dihindari. Sampau saat ini penentuan saat inisiasi acute renal replacement therapy (ARRT) masih kontroversial, demikian pula nilai ambang spesifik untuk memulainya belum sepenuhnya disepakati. Kata kunci: gagal ginjal akut; penyakit kritis' laju filtrasi glomerulus (LFG)  Abstract: Acute kidney injury (AKI) is a common problem in clinical practice, but its diagnosis could be delayed due to the inherent limitation of current diagnostic tools. Current practice suggests that RIFLE, AKIN, and KDIGO diagnostic criteria used to assess the presence of AKI and its severity are insufficient to illustrate the complexity of the AKI syndrome. Proteinuria and micro-albuminuria, classical markers of chronic kidney disease (CKD) progression, have been used and validated for the progression of AKI to CKD. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and urinary cystatin C could play a role in prediction of renal recovery. Indication of renal biopsy in critically ill patients are unexplained renal impairment or progression of CKD with both glomerular hematuria and proteinuria more than 1 gr per day, renal manifestations of life threathening systemic disease, suspected acute or chronic rejection of a transplanted kidney. The maintenance of adequate hemodynamics should be beneficial in preventing the onset or the worsening of AKI, but fluid overload should be avoided. Timing of acute renal replacement therapy (ARRT) initiation is still controversial, moreover, specific thresholds for starting are still unclear.Keywords: acute kidney injury (AKI); critically ill; glomerular filtration rate (GFR)

Early Detection of Renal Dysfunction in β Thalassemia with Focus on Novel Biomarkers

2020 ◽  
Author(s):  
Mozhgan Hashemieh
Keyword(s):  
Renal Dysfunction ◽  
Early Recognition ◽  
Binding Protein ◽  
Kidney Injury ◽  
Thalassemia Major ◽  
Retinol Binding Protein ◽  
Fatty Acid Binding ◽  
Novel Biomarkers ◽  
Beta 2 Microglobulin ◽  
Kidney Injury Molecule 1

Improved survival among transfusion dependent thalassemia patients in recent years has led to the manifestation of morbidities such as renal dysfunction. Renal injury is still an underestimated complication in β thalassemia major patients. Chronic anemia, iron overload due to repeated transfusion, and specific iron chelators are the main factors in pathogenesis of renal dysfunction in β thalassemia. Early identification of this morbidity allows us to delay the progression of kidney damage and therefore reduce renal impairment. In recent decades , novel biomarkers for early recognition of renal dysfunction have been studied in thalassemic patients, such as cystatin C, beta 2 microglobulin , alpha 1 microglobulin, N-acetyl beta-D-glucosaminidase (NAG), neutrophil gelatinase associated lipocaline (NGAL) , kidney injury molecule 1 (KIM-1) , liver type fatty acid binding protein (L-FABP), and retinol binding protein (RBP). In this review, renal aspects of thalassemia with focus on novel biomarkers were discussed.

scholarly journals Systemic and Urinary Neutrophil Gelatinase-Associated Lipocalins Are Poor Predictors of Acute Kidney Injury in Unselected Critically Ill Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Annick A. Royakkers ◽  
Catherine S. Bouman ◽  
Pauline M. Stassen ◽  
Joke C. Korevaar ◽  
Jan M. Binnekade ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Secondary Analysis ◽  
Kidney Injury ◽  
Observational Cohort Study ◽  
Prospective Observational Cohort Study ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Observational Cohort ◽  
Neutrophil Gelatinase

Background. Neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine have been suggested as potential early predictive biological markers of acute kidney injury (AKI) in selected critically ill patients.Methods. We performed a secondary analysis of a multicenter prospective observational cohort study of unselected critically ill patients.Results. The analysis included 140 patients, including 57 patients who did not develop AKI, 31 patients who developed AKI, and 52 patients with AKI on admission to the ICU. Levels of sNGAL and uNGAL on non-AKI days were significantly lower compared to levels of sNGAL on RIFLERISKdays, RIFLEINJURYdays, and RIFLEFAILUREdays. The AUC of sNGAL for predicting AKI was low: 0.45 (95% confidence interval (CI) 0.27–0.63) and 0.53 (CI 0.38–0.67), 2 days and 1 day before development of AKI, respectively. The AUC of uNGAL for predicting AKI was also low: 0.48 (CI 0.33–0.62) and 0.48 (CI 0.33–0.62), 2 days and 1 day before development of AKI, respectively. AUC of sNGAL and uNGAL for the prediction of renal replacement therapy requirement was 0.47 (CI 0.37–0.58) and 0.26 (CI 0.03–0.50).Conclusions. In unselected critically ill patients, sNGAL and uNGAL are poor predictors of AKI or RRT.

scholarly journals Screening of early diagnostic markers of gentamicin-induced acute kidney injury in canines

2019 ◽  
Vol 63 (3) ◽  
pp. 405-411
Author(s):  
Jia-San Zheng ◽  
Jing-Nie ◽  
Ting-Ting Zhu ◽  
Hong-Ri Ruan ◽  
Xue-Wei ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Characteristic Curve ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Fatty Acid Binding ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Transmission Electron ◽  
Renal Tubular ◽  
Kidney Injury Molecule 1 ◽  
Neutrophil Gelatinase

Abstract Introduction The value of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), and liver-type fatty acid binding protein (L-FABP) was assessed in early diagnosis of gentamicin-induced acute kidney injury (AKI) in dogs. Material and Methods Subcutaneous gentamicin injection in 16 healthy adult beagles made the AKI model. Blood was sampled every 6 h to detect NGAL, Kim-1, L-FABP, and serum creatinine (SCr) concentrations. Kidney tissue of two dogs was taken before the injection, as soon as SCr was elevated (78 μmol/L), and when it had risen to 1.5 times the baseline, and haematoxylin-eosin staining and transmission electron microscopy (TEM) were used to observe changes. Results NGAL, Kim-1, and SCr levels were significantly increased (P < 0.05) at 18, 30, and 78 h post injection, but L-FABP concentration was not associated with renal injury. At the earliest SCr elevation stage, findings were mild oedema, degeneration, and vacuolisation in renal tubular epithelial cells in pathology, and mild cytoplasmic and mitochondrial oedema in TEM. At this time point, NGAL and Kim-1 concentrations were significantly increased (P < 0.05), indicating that these two molecules biomark early kidney injury in dogs. Using receiver operating characteristic curve analysis, their warning levels were > 25.31 ng/mL and > 48.52 pg/mL. Conclusion Plasma NGAL and Kim-1 above warning levels are early indicators of gentamicin-induced AKI in dogs.

scholarly journals Comparison of Neutrophil Gelatinase-associated Lipocalin and Renal Resistive Index as Acute Kidney Injury Predictor in Critically Ill Patients at ICU H. Adam Malik Hospital Medan

2021 ◽  
Vol 9 (B) ◽  
pp. 1637-1639
Author(s):  
Muhammad Aldi Rivai Ginting ◽  
Achsanuddin Hanafie ◽  
Bastian Lubis
Keyword(s):  
Acute Kidney Injury ◽  
Serum Creatinine ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Resistive Index ◽  
Kidney Injury ◽  
Renal Resistive Index ◽  
Ngal Level ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Neutrophil Gelatinase

BACKGROUND: Acute kidney injury (AKI) is a complication found in critically ill patients. Current consensus explains that diagnosis of AKI based on increased serum creatinine and decreased urine output. Neutrophil gelatinase-associated lipocalin (NGAL) level is increased a few hours after tubular damage occurred and can predict AKI more significantly than serum creatinine. Renal resistive index (RRI) is also a good marker in predicting the early stage of AKI. AIM: This study aimed to compare RRI and NGAL level as marker to predict incidence of AKI in critically ill patients treated in the Intensive Care Unit (ICU) at H. Adam Malik Hospital Medan. METHODS: This was an observational prospective cohort study and conducted in ICU at H. Adam Malik Hospital Medan in April-May 2021. This study had been approved by the Ethics Committee of Faculty of Medicine, Sumatera Utara University and H. Adam Malik Hospital Medan. Inclusion criteria are critical patients aged 18–65 years with 1st and 2nd priority level. Consecutive sampling was used. Resistive Index (RI) measured using USG Doppler by researcher and the results confirmed by ICU supervisors, while urine NGAL level measured within 3 h after ICU admission. Plasma urea and creatinine level measured after 24h after ICU admission. RESULTS: A total of 40 samples were collected; percentage of men and women are 66–35%, respectively (p = 0.001). There was a significant difference RI between AKI-group and non-AKI group (0.719 ± 0.060 and 0.060 ± 0.077, respectively) (p = 0.001). RI has a sensitivity of 71%, specificity of 84%, and accuracy of 87% in predicting occurrence of AKI with AUROC = 0.873. Meanwhile, NGAL has a sensitivity, specificity, and accuracy (66%, 89%, 78%, respectively) in early prediction of AKI incidence in critically ill patients. CONCLUSION: RI value was higher in AKI group than non-AKI group. RRI has better sensitivity than NGAL in predicting incidence of AKI.

scholarly journals Potential Prognostic Markers of Acute Kidney Injury in the Early Phase of Acute Pancreatitis

2019 ◽  
Vol 20 (15) ◽  
pp. 3714 ◽  
Author(s):  
Justyna Wajda ◽  
Paulina Dumnicka ◽  
Małgorzata Maraj ◽  
Piotr Ceranowicz ◽  
Marek Kuźniewski ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Acute Pancreatitis ◽  
Binding Protein ◽  
Kidney Injury ◽  
Current Evidence ◽  
Serum Cystatin C ◽  
Fatty Acid Binding ◽  
Number Of Patients ◽  
Kidney Injury Molecule 1 ◽  
The Impact

Acute kidney injury (AKI) is a serious complication of acute pancreatitis (AP), which occurs in up to 70% of patients with severe AP and significantly increases the risk of mortality. At present, AKI is diagnosed based on dynamic increase in serum creatinine and decreased urine output; however, there is a need for earlier and more accurate biomarkers. The aim of the study was to review current evidence on the laboratory tests that were studied as the potential biomarkers of AKI in AP. We also briefly summarized the knowledge coming from the studies including sepsis or ICU patients since severe acute pancreatitis is associated with systemic inflammation and organ failure. Serum cystatin C and serum or urine NGAL have been shown to predict or diagnose AKI in AP; however, this evidence come from the single center studies of low number of patients. Other markers, such as urinary kidney injury molecule-1, cell cycle arrest biomarkers (tissue inhibitor metalloproteinase-2 and urine insulin-like growth factor-binding protein 7), interleukin-18, liver-type fatty acid-binding protein, or calprotectin have been studied in other populations suffering from systemic inflammatory states. In AP, the potential markers of AKI may be significantly influenced by either dehydration or inflammation, and the impact of these factors may be difficult to distinguish from kidney injury. The subject of AKI complicating AP is understudied. More studies are needed, for both exploratory (to choose the best markers) and clinical (to evaluate the diagnostic accuracy of the chosen markers in real clinical settings).

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