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Sodhi K, Chanchalani G, Tyagi N. Current role of biomarkers in the initiation and weaning of kidney replacement therapy in acute kidney injury. World J Nephrol 2025; 14:99802. [PMID: 40134642 PMCID: PMC11755245 DOI: 10.5527/wjn.v14.i1.99802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 10/16/2024] [Accepted: 11/12/2024] [Indexed: 01/20/2025] Open
Abstract
The occurrence of acute kidney injury (AKI) in critically ill patients is often associated with increased morbidity and mortality rates. Despite extensive research, a consensus is yet to be arrived, especially regarding the optimal timing and indications for initiation of kidney replacement therapy (KRT) for critically ill patients. There is no clear guidance available on the timing of weaning from KRT. More recently, various biomarkers have produced promising prognostic prediction in such patients, regarding the need for KRT and its termination. Most of these biomarkers are indicative of kidney damage and stress, rather than recovery. However, large-scale validation studies are required to guide the cutoff values of these biomarkers among different patient cohorts so as to identify the optimum timing for KRT. This article reviews the kidney biomarkers in detail and summarizes the individual roles of biomarkers in the decision-making process for initiation and termination of the KRT among critically ill AKI patients and the supportive literature.
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Affiliation(s)
- Kanwalpreet Sodhi
- Department of Critical Care, Deep Hospital, Ludhiana 141002, Punjab, India
| | - Gunjan Chanchalani
- Department of Critical Care Medicine, Karamshibhai Jethabhai Somaiya Hospital and Research Centre, Mumbai 400022, India
| | - Niraj Tyagi
- Department of Critical Care Medicine, Sir Ganga Ram Hospital, New Delhi 110060, Delhi, India
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Mitra R, Tholouli E, Rajai A, Saha A, Mitra S, Mitsides N. Urinary L-FABP Assay in the Detection of Acute Kidney Injury following Haematopoietic Stem Cell Transplantation. J Pers Med 2024; 14:1046. [PMID: 39452553 PMCID: PMC11508925 DOI: 10.3390/jpm14101046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Revised: 09/13/2024] [Accepted: 10/06/2024] [Indexed: 10/26/2024] Open
Abstract
Background: Acute Kidney Injury (AKI) is a condition that affects a significant proportion of acutely unwell patients and is associated with a high mortality rate. Patients undergoing haemopoietic stem cell transplantation (HSCT) are in an extremely high group for AKI. Identifying a biomarker or panel of markers that can reliably identify at-risk individuals undergoing HSCT can potentially impact management and outcomes. Early identification of AKI can reduce its severity and improve prognosis. We evaluated the urinary Liver type fatty acid binding protein (L-FABP), a tubular stress and injury biomarker both as an ELISA and a point of care (POC) assay for AKI detection in HSCT. Methods: 85 patients that had undergone autologous and allogenic HSCT (35 and 50, respectively) had urinary L-FABP (uL-FABP) measured by means of a quantitative ELISA and a semi-quantitative POC at baseline, day 0 and 7 post-transplantation. Serum creatinine (SCr) was also measured at the same time. Patients were followed up for 30 days for the occurrence of AKI and up to 18 months for mortality. The sensitivity and specificity of uL-FABP as an AKI biomarker were evaluated and compared to the performance of sCr using ROC curve analysis and logistic regression. Results: 39% of participants developed AKI within 1 month of their transplantation. The incidence of AKI was higher in the allogenic group than in the autologous HTSC group (57% vs. 26%, p = 0.008) with the median time to AKI being 25 [range 9-30] days. This group was younger (median age 59 vs. 63, p < 0.001) with a lower percentage of multiple myeloma as the primary diagnosis (6% vs. 88%, p < 0.001). The median time to AKI diagnosis was 25 [range 9-30] days. uL-FABP (mcg/gCr) at baseline, day of transplant and on the 7th day post-transplant were 1.61, 5.39 and 10.27, respectively, for the allogenic group and 0.58, 4.36 and 5.14 for the autologous group. Both SCr and uL-FABP levels rose from baseline to day 7 post-transplantation, while the AUC for predicting AKI for baseline, day 0 and day 7 post-transplant was 0.54, 0.59 and 0.62 for SCr and for 0.49, 0.43 and 0.49 uL-FABP, respectively. Univariate logistic regression showed the risk of AKI to be increased in patients with allogenic HSCT (p = 0.004, 95%CI [0.1; 0.65]) and in those with impaired renal function at baseline (p = 0.01, 95%CI [0.02, 0.54]). The risk of AKI was also significantly associated with SCr levels on day 7 post-transplant (p = 0.03, 95%CI [1; 1.03]). Multivariate logistic regression showed the type of HSCT to be the strongest predictor of AKI at all time points, while SCr levels at days 0 and 7 also correlated with increased risk in the model that included uL-FABP levels at the corresponding time points. The POC device for uL-FABP measurement correlated with ELISA (p < 0.001, Spearman 'correlation' = 0.54) Conclusions: The urinary biomarker uL-FABP did not demonstrate an independent predictive value in the detection of AKI at all stages. The most powerful risk predictor of AKI in this setting appears to be allograft recipients and baseline renal impairment, highlighting the importance of clinical risk stratification. Urinary L-FAPB as a POC biomarker was comparable to ELISA, which provides an opportunity for simple and rapid testing. However, the utility of LFABP in AKI is unclear and needs further exploration. Whether screening through rapid testing of uL-FABP can prevent or reduce AKI severity is unknown and merits further studies.
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Affiliation(s)
- Roshni Mitra
- Department of Haemato-Oncology, St Bartholomew’s Hospital, Barts Health NHS Trust, London EC1A 7BE, UK
| | - Eleni Tholouli
- Department of Haematology, Manchester University Hospitals, Oxford Road, Manchester M13 9WL, UK;
| | - Azita Rajai
- Research and Innovation, Manchester University Hospitals, Oxford Road, Manchester M13 9WL, UK
| | - Ananya Saha
- Manchester Academy of Health Sciences, Manchester University Hospitals, University of Manchester, Manchester M13 9WL, UK (S.M.)
| | - Sandip Mitra
- Manchester Academy of Health Sciences, Manchester University Hospitals, University of Manchester, Manchester M13 9WL, UK (S.M.)
| | - Nicos Mitsides
- Medical School, University of Cyprus, Nicosia 2029, Cyprus
- Nephrology Department, Nicosia General Hospital, Nicosia 2029, Cyprus
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Janfeshan S, Afshari A, Yaghobi R, Roozbeh J. Urinary CXCL-10, a prognostic biomarker for kidney graft injuries: a systematic review and meta-analysis. BMC Nephrol 2024; 25:292. [PMID: 39232662 PMCID: PMC11375915 DOI: 10.1186/s12882-024-03728-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 08/26/2024] [Indexed: 09/06/2024] Open
Abstract
The challenges of long-term graft survival and the side effects of current immunosuppressive therapies in kidney transplantation highlight the need for improved drugs with fewer adverse effects. Biomarkers play a crucial role in quickly detecting post-transplant complications, with new biomarkers showing promise for ongoing monitoring of disease and potentially reducing the need for unnecessary invasive biopsies. The chemokines such as C-X-C motif chemokine ligand 10 (CXCL10), are particularly promising protein biomarkers for acute renal rejection, with urine samples being a desirable source for biomarkers. The aim of this review is to analyze the literature on the potential role of urinary CXCL10 protein in predicting kidney graft injuries. The results of this study demonstrate that evaluating urinary CXCL10 levels is more successful in identifying post-transplant injuries compared to assessing the CXCL10/Cr ratio.
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Affiliation(s)
- Sahar Janfeshan
- Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Afsoon Afshari
- Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Ramin Yaghobi
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Jamshid Roozbeh
- Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Rivetti G, Gizzone P, Petrone D, Di Sessa A, Miraglia del Giudice E, Guarino S, Marzuillo P. Acute Kidney Injury in Children: A Focus for the General Pediatrician. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1004. [PMID: 39201939 PMCID: PMC11352805 DOI: 10.3390/children11081004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 07/31/2024] [Accepted: 08/13/2024] [Indexed: 09/03/2024]
Abstract
Acute kidney injury (AKI) presents significant challenges in pediatric care, often remaining underrecognized. This paper provides an overview of pediatric AKI, highlighting its epidemiology, pathophysiology, diagnosis, predisposing conditions, and treatment. AKI in children stems from diverse causes, including renal tubular damage, vasoconstriction, and inflammation. Diagnosis relies on traditional markers such as serum creatinine and urine output, alongside emerging biomarkers such as Cystatin C, NGAL, KIM-1, IL-18, TIMP-2 and IGFBP7, urinary calprotectin, URBP4, L-FABP, and clusterin. Various pediatric conditions predispose to AKI, including type 1 diabetes, pneumonia, bronchiolitis, appendicitis, gastroenteritis, COVID-19, multisystem inflammatory syndrome, sickle cell disease, and malignancies. Treatment entails supportive care with fluid management and, in severe cases, renal replacement therapy. Timely recognition and management are essential to mitigating adverse outcomes. Enhanced awareness and integration of novel biomarkers could improve pediatric AKI care, warranting further research for better diagnosis and management.
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Affiliation(s)
| | | | | | | | | | | | - Pierluigi Marzuillo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, Via Luigi de Crecchio 2, 80138 Naples, Italy; (G.R.); (P.G.); (D.P.); (A.D.S.); (E.M.d.G.); (S.G.)
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Scurt FG, Bose K, Mertens PR, Chatzikyrkou C, Herzog C. Cardiac Surgery-Associated Acute Kidney Injury. KIDNEY360 2024; 5:909-926. [PMID: 38689404 PMCID: PMC11219121 DOI: 10.34067/kid.0000000000000466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 04/26/2024] [Indexed: 05/02/2024]
Abstract
AKI is a common and serious complication of cardiac surgery that has a significant impact on patient morbidity and mortality. The Kidney Disease Improving Global Outcomes definition of AKI is widely used to classify and identify AKI associated with cardiac surgery (cardiac surgery-associated AKI [CSA-AKI]) on the basis of changes in serum creatinine and/or urine output. There are various preoperative, intraoperative, and postoperative risk factors for the development of CSA-AKI which should be recognized and addressed as early as possible to expedite its diagnosis, reduce its occurrence, and prevent or ameliorate its devastating complications. Crucial issues are the inaccuracy of serum creatinine as a surrogate parameter of kidney function in the perioperative setting of cardiothoracic surgery and the necessity to discover more representative markers of the pathophysiology of AKI. However, except for the tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 ratio, other diagnostic biomarkers with an acceptable sensitivity and specificity are still lacking. This article provides a comprehensive review of various aspects of CSA-AKI, including pathogenesis, risk factors, diagnosis, biomarkers, classification, prevention, and treatment management.
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Affiliation(s)
- Florian G. Scurt
- Clinic of Nephrology, Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Katrin Bose
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Magdeburg, Germany
| | - Peter R. Mertens
- Clinic of Nephrology, Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Christos Chatzikyrkou
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
| | - Carolin Herzog
- Clinic of Nephrology, Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
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Tăluță C, Ștefănescu H, Crișan D. Seeing and Sensing the Hepatorenal Syndrome (HRS): The Growing Role of Ultrasound-Based Techniques as Non-Invasive Tools for the Diagnosis of HRS. Diagnostics (Basel) 2024; 14:938. [PMID: 38732353 PMCID: PMC11083774 DOI: 10.3390/diagnostics14090938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 04/23/2024] [Accepted: 04/26/2024] [Indexed: 05/13/2024] Open
Abstract
More than half of patients hospitalized with liver cirrhosis are dealing with an episode of acute kidney injury; the most severe pattern is hepatorenal syndrome due to its negative prognosis. The main physiopathology mechanisms involve renal vasoconstriction and systemic inflammation. During the last decade, the definition of hepatorenal syndrome changed, but the validated criteria of diagnosis are still based on the serum creatinine level, which is a biomarker with multiple limitations. This is the reason why novel serum and urinary biomarkers have been intensively studied in recent years. Meanwhile, the imaging studies that use shear wave elastography are using renal stiffness as a surrogate for an early diagnosis. In this article, we focus on the physiopathology definition and highlight the novel tools used in the diagnosis of hepatorenal syndrome.
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Affiliation(s)
- Cornelia Tăluță
- Liver Unit, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania;
| | - Horia Ștefănescu
- Liver Unit, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania;
| | - Dana Crișan
- 5th Medical Clinic, Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400139 Cluj-Napoca, Romania;
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Erfurt S, Lauxmann M, Asmus K, Oess S, Patschan D, Hoffmeister M. Serum Nostrin-A risk factor of death, kidney replacement therapy and acute kidney disease in acute kidney injury. PLoS One 2024; 19:e0299131. [PMID: 38603667 PMCID: PMC11008819 DOI: 10.1371/journal.pone.0299131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 03/26/2024] [Indexed: 04/13/2024] Open
Abstract
BACKGROUND The prediction of Acute Kidney Injury (AKI)-related outcomes remains challenging. Persistent kidney excretory dysfunction for longer than 7 days has been defined as Acute Kidney Disease (AKD). In this study, we prospectively quantified serum Nostrin, an essential regulator of endothelial NO metabolism, in hospitalized patients with AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In-hospital subjects with AKI of various etiology were identified through the in-hospital AKI alert system of the Brandenburg University Hospital. Serum Nostrin, and serum NGAL and KIM-1 were measured within a maximum of 48 hours from the timepoint of initial diagnosis of AKI. The following endpoints were defined: in-hospital death, need of kidney replacement therapy (KRT), recovery of kidney function (ROKF) until discharge. RESULTS AKI patients had significantly higher serum Nostrin levels compared to Controls. The level of serum Nostrin increased significantly with the severity of AKI. Within the group of AKI patients (n = 150) the in-hospital mortality was 16.7%, KRT was performed in 39.3%, no ROKF occurred in 28%. Patients who required KRT had significantly higher levels of serum Nostrin compared to patients who did not require KRT. Significantly higher levels of serum Nostrin were also detected in AKI patients without ROKF compared to patients with ROKF. In addition, low serum Nostrin levels at the timepoint of AKI diagnosis were predictive of in-hospital survival. For comparison, the serum concentrations of NGAL and KIM-1 were determined in parallel to the Nostrin concentrations and the results confirm the prognostic properties of serum Nostrin in AKI. CONCLUSIONS The current study suggests serum Nostrin as novel biomarker of AKI-associated mortality, KRT and Acute Kidney Disease.
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Affiliation(s)
- Stefan Erfurt
- Brandenburg Medical School Theodor Fontane, Institute of Biochemistry, Brandenburg an der Havel, Germany
- Department of Internal Medicine I—Cardiology, Nephrology and Internal Intensive Medicine, Brandenburg University Hospital, Brandenburg Medical School Theodor Fontane, Brandenburg an der Havel, Germany
| | - Martin Lauxmann
- Brandenburg Medical School Theodor Fontane, Institute of Biochemistry, Brandenburg an der Havel, Germany
- Department of Internal Medicine I—Cardiology, Nephrology and Internal Intensive Medicine, Brandenburg University Hospital, Brandenburg Medical School Theodor Fontane, Brandenburg an der Havel, Germany
| | - Katharina Asmus
- Department of Internal Medicine I—Cardiology, Nephrology and Internal Intensive Medicine, Brandenburg University Hospital, Brandenburg Medical School Theodor Fontane, Brandenburg an der Havel, Germany
| | - Stefanie Oess
- Brandenburg Medical School Theodor Fontane, Institute of Biochemistry, Brandenburg an der Havel, Germany
- Faculty of Health Sciences (FGW), Joint Faculty of the University of Potsdam, The Brandenburg Medical School Theodor Fontane and the Brandenburg Technical University, Cottbus-Senftenberg, Germany
| | - Daniel Patschan
- Department of Internal Medicine I—Cardiology, Nephrology and Internal Intensive Medicine, Brandenburg University Hospital, Brandenburg Medical School Theodor Fontane, Brandenburg an der Havel, Germany
- Faculty of Health Sciences (FGW), Joint Faculty of the University of Potsdam, The Brandenburg Medical School Theodor Fontane and the Brandenburg Technical University, Cottbus-Senftenberg, Germany
| | - Meike Hoffmeister
- Brandenburg Medical School Theodor Fontane, Institute of Biochemistry, Brandenburg an der Havel, Germany
- Faculty of Health Sciences (FGW), Joint Faculty of the University of Potsdam, The Brandenburg Medical School Theodor Fontane and the Brandenburg Technical University, Cottbus-Senftenberg, Germany
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Wejnaruemarn S, Prasoppokakorn T, Srisawat N, Teerasarntipan T, Thanapirom K, Phathong C, Chaiteerakij R, Komolmit P, Tangkijvanich P, Treeprasertsuk S. Urine Liver-Type Fatty Acid Binding Protein; Biomarker for Diagnosing Acute Kidney Injury and Predicting Mortality in Cirrhotic Patients. SIRIRAJ MEDICAL JOURNAL 2024; 76:198-208. [DOI: 10.33192/smj.v76i4.268004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2025] Open
Abstract
Objective: To determine impact of urine liver-type fatty acid binding protein (uL-FABP) and urine neutrophil gelatinase-associated lipocalin (uNGAL), which were biomarkers linked to acute kidney injury (AKI), in AKI diagnosis and prediction of 28-day mortality among hospitalized cirrhotic patients.
Materials and Methods: We prospectively enrolled hospitalized cirrhotic patients at a tertiary care university hospital between June 2018 and November 2019. The uL-FABP, uNGAL, and plasma NGAL (pNGAL) were collected within 48 hours of admission. Cutoff values of biomarkers for diagnosing AKI derived from receiver operating characteristic (ROC) curve. Logistic regression analysis was used to identify independent factors for 28-day mortality.
Results: We enrolled 109 cirrhotic patients in derivative cohort, 41.3% had AKI. Median uL-FABP, uNGAL, and pNGAL levels in AKI group were higher than non-AKI group: 8.1 vs. 2.8 ng/mL (p=0.002), 40.5 vs. 10.1 ng/mL (p<0.001), and 195.7 vs 81.4 ng/mL (p=0.001), respectively. Areas under the ROC curve of uL-FABP, uNGAL, and pNGAL for AKI diagnosis were 0.68, 0.73 and 0.68, respectively. Also, all biomarkers were significantly higher in mortality group. Multivariate analysis showed that the only independent predictor for 28-day mortality was uL-FABP ≥ 4.68 ng/mL (odd ratio 4.15, p=0.02).
Conclusion: UL-FABP, uNGAL, and pNGAL are associated with AKI in hospitalized cirrhotic patients. Moreover, uL-FABP ≥ 4.68 ng/mL was a significant independent predictor for 28-day mortality.
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Ru S, Lv S, Li Z. Incidence, mortality, and predictors of acute kidney injury in patients with heart failure: a systematic review. ESC Heart Fail 2023; 10:3237-3249. [PMID: 37705352 PMCID: PMC10682870 DOI: 10.1002/ehf2.14520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 05/22/2023] [Accepted: 08/04/2023] [Indexed: 09/15/2023] Open
Abstract
Acute kidney injury (AKI) is common in patients with heart failure (HF), but studies have been inconsistent about the incidence of AKI in patients with HF. We conducted a meta-analysis to examine the incidence of AKI and its impact on mortality in patients with HF. We also looked at inpatient variables that could predict the development of AKI to identify potential risk factors, so that these can be used as a starting point for intervention and prevention in this group. The Embase, Medline, PubMed, Cochrane libraries, and Web of Science databases were used for searching articles from the inception of the database to October 2022. The EndNote software was used for screening. Meta-analysis was performed using Stata 16.0 software to combine effect sizes. A total of 37 studies were included. Of all the 3 533 583 patients with HF, 774 887 had AKI, with a pooled incidence of 33% [95% confidence interval (CI): 32-35%]. The incidence rate of AKI in acute HF and chronic HF was 36% (95% CI: 31-40%) and 30% (95% CI: 24-35%), respectively. Eleven studies found that AKI patients had higher in-hospital mortality than non-AKI patients [risk ratio (RR): 3.65; 95% CI: 3.04-4.39, P < 0.001]. Mortality was assessed in five studies, and it was found that mortality remained high at 1-year follow-up after onset of AKI (RR: 1.85, 95% CI: 1.54-2.22, P < 0.001). Fifteen admission variables were included and analysed in 13 studies. The combined results showed that diabetes, hypertension, history of chronic kidney disease, chronic HF systolic, age, N-terminal pro-B-type natriuretic peptide, creatinine > 1.0 mg/dL, index estimated glomerular filtration rate < 60 mL/min/1.73 m2 , blood urea nitrogen > 24 mg/dL, intravenous dobutamine, and serum albumin were predictor factors for HF patients with AKI (P < 0.05). In this meta-analysis, AKI occurred in approximately 33% of HF patients during hospitalization and the risk of dying in the hospital was tripled. Even during 1-year long-term follow-up, the risk of death remained high, and multiple inpatient variables showed that HF patients tended to have AKI. Early intervention and treatment are important to reduce the incidence of AKI and improve the prognosis.
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Affiliation(s)
- Song‐Chao Ru
- Department of CardiologyThe First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and TechnologyLuoyangChina
| | - Shu‐Bin Lv
- Department of CardiologyThe First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and TechnologyLuoyangChina
| | - Zhi‐Juan Li
- Department of CardiologyThe First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and TechnologyLuoyangChina
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Agborbesong E, Bissler J, Li X. Liquid Biopsy at the Frontier of Kidney Diseases: Application of Exosomes in Diagnostics and Therapeutics. Genes (Basel) 2023; 14:1367. [PMID: 37510273 PMCID: PMC10379367 DOI: 10.3390/genes14071367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 06/08/2023] [Accepted: 06/26/2023] [Indexed: 07/30/2023] Open
Abstract
In the era of precision medicine, liquid biopsy techniques, especially the use of urine analysis, represent a paradigm shift in the identification of biomarkers, with considerable implications for clinical practice in the field of nephrology. In kidney diseases, the use of this non-invasive tool to identify specific and sensitive biomarkers other than plasma creatinine and the glomerular filtration rate is becoming crucial for the diagnosis and assessment of a patient's condition. In recent years, studies have drawn attention to the importance of exosomes for diagnostic and therapeutic purposes in kidney diseases. Exosomes are nano-sized extracellular vesicles with a lipid bilayer structure, composed of a variety of biologically active substances. In the context of kidney diseases, studies have demonstrated that exosomes are valuable carriers of information and are delivery vectors, rendering them appealing candidates as biomarkers and drug delivery vehicles with beneficial therapeutic outcomes for kidney diseases. This review summarizes the applications of exosomes in kidney diseases, emphasizing the current biomarkers of renal diseases identified from urinary exosomes and the therapeutic applications of exosomes with reference to drug delivery and immunomodulation. Finally, we discuss the challenges encountered when using exosomes for therapeutic purposes and how these may affect its clinical applications.
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Affiliation(s)
- Ewud Agborbesong
- Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
| | - John Bissler
- Department of Pediatrics, University of Tennessee Health Science Center and Le Bonheur Children's Hospital, Memphis, TN 38105, USA
- Children's Foundation Research Institute, Le Bonheur Children's Hospital, Memphis, TN 38105, USA
- Pediatric Medicine Department, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Xiaogang Li
- Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
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Patschan D, Erfurt S, Oess S, Lauxmann M, Patschan S, Ritter O, Hoffmeister M. Biomarker-Based Prediction of Survival and Recovery of Kidney Function in Acute Kidney Injury. Kidney Blood Press Res 2023; 48:124-134. [PMID: 36758525 DOI: 10.1159/000528633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 12/06/2022] [Indexed: 02/11/2023] Open
Abstract
BACKGROUND Acute kidney injury (AKI) affects increasing numbers of hospitalized patients; the prognosis remains poor. The diagnosis is still based on the 2012 published KDIGO criteria. Numerous new AKI biomarkers have been identified in recent years; they either reflect impaired excretory function or structural damage. The majority of markers are useful for AKI recognition under certain circumstances. Fewer data are available on the role of biomarkers in the prediction of in-hospital survival and renal recovery post-AKI. The current article is intended to provide information about these two aspects. SUMMARY The following databases were screened: PubMed, Web of Science, Cochrane Library, Scopus. The period lasted from 2000 until 2022. The following terms were applied: "AKI" AND "biomarker" AND "survival" OR "mortality" OR "recovery of kidney function" OR "renal recovery" OR "kidney recovery". The following terms were used for additional literature search: "TIMP-2" AND "IGFBP7" and "RNA biomarker" AND "hematology". Regarding mortality, exclusively those studies were selected that addressed the in-hospital mortality. Nine (9) studies were identified that evaluated biomarker-based prediction of in-hospital mortality and/or of recovery of kidney function (ROKF). A homogenous definition of ROKF is however missing yet. Currently, some biomarkers, measured early during the course of the disease, are associated with increased mortality risk and/or with a higher chance of renal recovery. KEY MESSAGES The literature provides only a few biomarker-related studies that address the issues of mortality and recovery. The definition of ROKF needs to be homogenized.
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Affiliation(s)
- Daniel Patschan
- Department of Internal Medicine I - Cardiology, Nephrology and Internal Intensive Medicine Brandenburg University Hospital, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel, Germany
- Faculty of Health Sciences (FGW), Joint Faculty of the University of Potsdam, The Brandenburg Medical School Theodor Fontane and the Brandenburg Technical University Cottbus-Senftenberg, Cottbus, Germany
| | - Stefan Erfurt
- Department of Internal Medicine I - Cardiology, Nephrology and Internal Intensive Medicine Brandenburg University Hospital, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel, Germany
| | - Stefanie Oess
- Faculty of Health Sciences (FGW), Joint Faculty of the University of Potsdam, The Brandenburg Medical School Theodor Fontane and the Brandenburg Technical University Cottbus-Senftenberg, Cottbus, Germany
- Institute of Biochemistry, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel, Germany
| | - Martin Lauxmann
- Institute of Biochemistry, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel, Germany
| | - Susann Patschan
- Department of Internal Medicine I - Cardiology, Nephrology and Internal Intensive Medicine Brandenburg University Hospital, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel, Germany
| | - Oliver Ritter
- Department of Internal Medicine I - Cardiology, Nephrology and Internal Intensive Medicine Brandenburg University Hospital, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel, Germany
- Faculty of Health Sciences (FGW), Joint Faculty of the University of Potsdam, The Brandenburg Medical School Theodor Fontane and the Brandenburg Technical University Cottbus-Senftenberg, Cottbus, Germany
| | - Meike Hoffmeister
- Faculty of Health Sciences (FGW), Joint Faculty of the University of Potsdam, The Brandenburg Medical School Theodor Fontane and the Brandenburg Technical University Cottbus-Senftenberg, Cottbus, Germany
- Institute of Biochemistry, Brandenburg Medical School (Theodor Fontane), Brandenburg an der Havel, Germany
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12
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Rodrigues CE, Endre ZH. Definitions, phenotypes, and subphenotypes in acute kidney injury-Moving towards precision medicine. Nephrology (Carlton) 2023; 28:83-96. [PMID: 36370326 PMCID: PMC10100386 DOI: 10.1111/nep.14132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 10/23/2022] [Accepted: 10/31/2022] [Indexed: 11/13/2022]
Abstract
The current definition of acute kidney injury (AKI) is generic and, based only on markers of function, is unsuitable for guiding individualized treatment. AKI is a complex syndrome with multiple presentations and causes. Targeted AKI management will only be possible if different phenotypes and subphenotypes of AKI are recognised, based on causation and related pathophysiology. Molecular signatures to identify subphenotypes are being recognised, as specific biomarkers reveal activated pathways. Assessment of individual clinical risk needs wider dissemination to allow identification of patients at high risk of AKI. New and more timely markers for glomerular filtration rate (GFR) are available. However, AKI diagnosis and classification should not be limited to GFR, but include tubular function and damage. Combining damage and stress biomarkers with functional markers enhances risk prediction, and identifies a population enriched for clinical trials targeting AKI. We review novel developments and aim to encourage implementation of these new techniques into clinical practice as a strategy for individualizing AKI treatment akin to a precision medicine-based approach.
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Affiliation(s)
- Camila Eleuterio Rodrigues
- Nephrology DepartmentPrince of Wales Clinical School – UNSW MedicineSydneyNew South WalesAustralia
- Nephrology DepartmentHospital das Clínicas – University of São Paulo School of MedicineSão PauloBrazil
| | - Zoltán H. Endre
- Nephrology DepartmentPrince of Wales Clinical School – UNSW MedicineSydneyNew South WalesAustralia
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13
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Liu Y, Yuan W, Fang M, Guo H, Zhang X, Mei X, Zhang Y, Ji L, Gao Y, Wang J, Qian Z, Li M, Gao Y. Determination of HMGB1 in hepatitis B virus-related acute-on-chronic liver failure patients with acute kidney injury: Early prediction and prognostic implications. Front Pharmacol 2023; 13:1031790. [PMID: 36712653 PMCID: PMC9880762 DOI: 10.3389/fphar.2022.1031790] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 12/13/2022] [Indexed: 01/15/2023] Open
Abstract
Background: Acute kidney injury (AKI) is a frequent complication in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and is associated with high rates of mortality. We aimed to estimate serum high mobility group protein 1 (HMGB1) levels in hepatitis B virus-related acute-on-chronic liver failure patients and analyze their clinical value in the development and outcomes of Acute kidney injury. Methods: A total of 251 consecutive patients with hepatitis B virus-related acute-on-chronic liver failure were enrolled in this retrospective study. Using the International Club of Ascites staging criteria of Acute kidney injury, 153 patients developed Acute kidney injury. The clinical data of patients were collected and serum levels of high mobility group protein 1 were measured by ELISA. All patients were followed up until death or for a minimum of 3 months. Early prediction and prognostic implications of high mobility group protein 1 in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure Patients with Acute Kidney Injury were investigated in different cohorts, including a propensity score-matched ACLF cohort. Results: Among all individuals with hepatitis B virus-related acute-on-chronic liver failure, the incidence of Acute kidney injury was 61.0% (153/251). The patients who developed stage 2/3 Acute kidney injury showed the highest high mobility group protein 1 levels, followed by those who developed stage 1 Acute kidney injury, and those without Acute kidney injury showed the lowest high mobility group protein 1 levels. Moreover, high mobility group protein 1 levels were significantly higher in non-survivors than in survivors among hepatitis B virus-related acute-on-chronic liver failure patients with Acute kidney injury. Furthermore, analysis of the area under the receiver operating characteristic curve (AUROC) indicated that serum high mobility group protein 1 levels (pre-matching: AUC = 0.740; post-matching: AUC = 0.661) may be a potential predictive factor for Acute kidney injury development and that high mobility group protein 1 (AUC = 0.727) might be a reliable biomarker for prognosis in patients with Acute kidney injury. Conclusion: In patients with hepatitis B virus-related acute-on-chronic liver failure, Acute kidney injury is universal. Acute kidney injury and its stages negatively influence the 90-day transplant-free mortality rate. Serum high mobility group protein 1 levels can serve as a positive predictor of Acute kidney injury development, and high mobility group protein 1 might also be a prognostic biomarker for Acute kidney injury among hepatitis B virus-related acute-on-chronic liver failure patients.
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Affiliation(s)
- Yu Liu
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China,Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Wei Yuan
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Miao Fang
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hongying Guo
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Xin Zhang
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xue Mei
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Yuyi Zhang
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Longshan Ji
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yating Gao
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiefei Wang
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Zhiping Qian
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China,*Correspondence: Zhiping Qian, ; Man Li, ; Yueqiu Gao,
| | - Man Li
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China,*Correspondence: Zhiping Qian, ; Man Li, ; Yueqiu Gao,
| | - Yueqiu Gao
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China,Institute of Infectious Diseases of Integrated Traditional Chinese and Western Medicine, Shanghai, China,*Correspondence: Zhiping Qian, ; Man Li, ; Yueqiu Gao,
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14
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Pan HC, Yang SY, Chiou TTY, Shiao CC, Wu CH, Huang CT, Wang TJ, Chen JY, Liao HW, Chen SY, Huang TM, Yang YF, Lin HYH, Chan MJ, Sun CY, Chen YT, Chen YC, Wu VC. Comparative accuracy of biomarkers for the prediction of hospital-acquired acute kidney injury: a systematic review and meta-analysis. Crit Care 2022; 26:349. [PMID: 36371256 PMCID: PMC9652605 DOI: 10.1186/s13054-022-04223-6] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 10/28/2022] [Indexed: 11/13/2022] Open
Abstract
Background Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to compare the predictive performance of different candidate biomarkers for AKI. Methods In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (> 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence. Results We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio [DOR] 16.2, 95% CI 10.1–25.9), urinary NGAL (DOR 13.8, 95% CI 10.2–18.8), and serum NGAL (DOR 12.6, 95% CI 9.3–17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively. Conclusions Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients. Trial registrationCRD42020207883, October 06, 2020. Supplementary Information The online version contains supplementary material available at 10.1186/s13054-022-04223-6.
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15
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Patel M, Gbadegesin RA. Update on prognosis driven classification of pediatric AKI. Front Pediatr 2022; 10:1039024. [PMID: 36340722 PMCID: PMC9634036 DOI: 10.3389/fped.2022.1039024] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 10/03/2022] [Indexed: 11/29/2022] Open
Abstract
Acute kidney injury (AKI) affects a large proportion of hospitalized children and increases morbidity and mortality in this population. Initially thought to be a self-limiting condition with uniformly good prognosis, we now know that AKI can persist and progress to acute kidney disease (AKD) and chronic kidney disease (CKD). AKI is presently categorized by stage of injury defined by increase in creatinine, decrease in eGFR, or decrease in urine output. These commonly used biomarkers of acute kidney injury do not change until the injury is well established and are unable to detect early stage of the disease when intervention is likely to reverse injury. The kidneys have the ability to compensate and return serum creatinine to a normal or baseline level despite nephron loss in the setting of AKI possibly masking persistent dysfunction. Though these definitions are important, classifying children by their propensity for progression to AKD and CKD and defining these risk strata by other factors besides creatinine may allow for better prognosis driven discussion, expectation setting, and care for our patients. In order to develop a classification strategy, we must first be able to recognize children who are at risk for AKD and CKD based on modifiable and non-modifiable factors as well as early biomarkers that identify their risk of persistent injury. Prevention of initial injury, prompt evaluation and treatment if injury occurs, and mitigating further injury during the recovery period may be important factors in decreasing risk of AKD and CKD after AKI. This review will cover presently used definitions of AKI, AKD, and CKD, recent findings in epidemiology and risk factors for AKI to AKD to CKD progression, novel biomarkers for early identification of AKI and AKI that may progress to CKD and future directions for improving outcome in children with AKI.
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Affiliation(s)
- Mital Patel
- Department of Pediatrics, Division of Pediatric Nephrology, Duke University, Durham, NC, United State
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16
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Point-of-Care (POC) Urinary L-Type Fatty Acid-Binding Protein (u-LFABP) Use in Critically Ill, Very Preterm Neonates. Int J Nephrol 2022; 2022:4684674. [PMID: 35345834 PMCID: PMC8957471 DOI: 10.1155/2022/4684674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 12/31/2021] [Accepted: 02/19/2022] [Indexed: 11/17/2022] Open
Abstract
Preterm neonates are born with fewer functional nephrons, rendering them vulnerable to secondary insult. These insults are associated with acute kidney injury (AKI); thus, structural damage must be detected as early as possible. Urinary L-type fatty acid-binding protein (u-LFABP) has been proposed as a highly suitable kidney injury biomarker during prematurity. We aimed to analyze the use of POC u-LFABP in critically ill, very preterm neonates. This study was conducted at the neonatal intensive care unit (NICU), Dr. Cipto Mangunkusumo General Hospital, from November to December 2020. Baseline characteristics were recorded from electronic medical records. u-LFABP examination utilized stored urine samples from a previous study and was performed using a LFABP POC test kit. The proportion of abnormal u-LFABP (83.3%) was highest at 72 hours. Neonates with older gestational age (0–48 hours;
) and higher birth weight (0–48 hours;
, 72 hours;
) had normal u-LFABP levels. Neonates exposed to nephrotoxic agents showed higher proportion of abnormal u-LFABP (0–48 hours;
). Longer invasive mechanical ventilation (IMV) period was observed in neonates with abnormal u-LFABP levels at 0–48 hours (7.44 ± 7.9 vs. 1.50 ± 2.9 days;
). We found an association between complication rates and poorer disease outcome trends with abnormal u-LFABP; however, this relationship was not supported statistically. In conclusion, this study demonstrated that u-LFABP can be detected using bedside POC kit in critically ill very preterm neonates and those exposed to nephrotoxic agents may be at risk for kidney injury, confirmed by abnormal u-LFABP levels.
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17
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Aldea PL, Rachisan AL, Stanciu BI, Picos A, Picos AM, Delean DI, Stroescu R, Starcea MI, Borzan CM, Elec FI. The Perspectives of Biomarkers in Predicting the Survival of the Renal Graft. Front Pediatr 2022; 10:869628. [PMID: 35722493 PMCID: PMC9204089 DOI: 10.3389/fped.2022.869628] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 05/09/2022] [Indexed: 11/13/2022] Open
Abstract
Kidney transplantation (KT) is currently the elective approach for patients with end-stage renal disease. Although it is a safe choice for these patients, the early complications can lead to graft dysfunction. One of the most redoubtable complications is delayed graft function (DGF), having no specific treatment. The effects of DGF on the graft survival are large enough to justify the formulation of specific biological protocols. Therefore, discovering biomarkers of acute impairment in renal transplanted patients is required. Creatinine is a poor marker to establish the kidney injury. Estimated glomerular filtration rate together with creatinine is ready to approximately measure the kidney function. Different serum and urine proteins are being studied as possible predictive biomarkers for delayed graft function. This review will concentrate on recent and existing research which provide insight concerning the contribution of some molecules for the estimation and evaluation of graft function after kidney transplantation. Further studies examining various aspects of DGF after KT are urgently needed to address a hitherto less-known clinical question.
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Affiliation(s)
- Paul Luchian Aldea
- Department of Community Medicine, Discipline of Public Health and Management, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Andreea Liana Rachisan
- Department of Mother and Child, Discipline of Pediatrics II, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Bogdan Ioan Stanciu
- Department of Radiology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Andrei Picos
- Department of Prevention in Dental Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Alina Monica Picos
- Department of Dental Prosthetics, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Dan Ioan Delean
- Department of Mother and Child, Discipline of Pediatrics II, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Ramona Stroescu
- Department of Pediatrics, Victor Babeş University of Medicine and Pharmacy, Timisoara, Romania
| | | | - Cristina Maria Borzan
- Department of Community Medicine, Discipline of Public Health and Management, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Florin Ioan Elec
- Department of Surgical Sciences, Discipline of Urology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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18
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Advances in pediatric acute kidney injury. Pediatr Res 2022; 91:44-55. [PMID: 33731820 DOI: 10.1038/s41390-021-01452-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 01/26/2021] [Accepted: 02/16/2021] [Indexed: 01/10/2023]
Abstract
The objective of this study was to inform the pediatric nephrologists of recent advances in acute kidney injury (AKI) epidemiology, pathophysiology, novel biomarkers, diagnostic tools, and management modalities. Studies were identified from PubMed, EMBASE, and Google Scholar for topics relevant to AKI. The bibliographies of relevant studies were also reviewed for potential articles. Pediatric (0-18 years) articles from 2000 to May 2020 in the English language were included. For epidemiological outcomes analysis, a meta-analysis on data regarding AKI incidence, mortality, and proportion of kidney replacement therapy was performed and an overall pooled estimate was calculated using the random-effects model. Other sections were created highlighting pathophysiology, novel biomarkers, changing definitions of AKI, evolving tools for AKI diagnosis, and various management modalities. AKI is a common condition seen in hospitalized children and the diagnosis and management have shown to be quite a challenge. However, new standardized definitions, advancements in diagnostic tools, and the development of novel management modalities have led to increased survival benefits in children with AKI. IMPACT: This review highlights the recent innovations in the field of AKI, especially in regard to epidemiology, pathophysiology, novel biomarkers, diagnostic tools, and management modalities.
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19
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Hara T, Uemoto R, Sekine A, Mitsui Y, Masuda S, Kurahashi K, Yoshida S, Otoda T, Yuasa T, Kuroda A, Ikeda Y, Endo I, Honda S, Yoshimoto K, Kondo A, Tamaki T, Matsumoto T, Matsuhisa M, Abe M, Aihara K. Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes. J Diabetes Investig 2021; 12:2172-2182. [PMID: 34043882 PMCID: PMC8668075 DOI: 10.1111/jdi.13602] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 05/10/2021] [Accepted: 05/20/2021] [Indexed: 12/01/2022] Open
Abstract
AIMS/INTRODUCTION Thrombin exerts various pathophysiological functions by activating protease-activated receptors (PARs). Recent data have shown that PARs influence the development of glomerular diseases including diabetic kidney disease (DKD) by regulating inflammation. Heparin cofactor II (HCII) specifically inactivates thrombin; thus, we hypothesized that low plasma HCII activity correlates with DKD development, as represented by albuminuria. MATERIALS AND METHODS Plasma HCII activity and spot urine biomarkers, including albumin and liver-type fatty acid-binding protein (L-FABP), were determined as the urine albumin-to-creatinine ratio (uACR) and the urine L-FABP-to-creatinine ratio (uL-FABPCR) in 310 Japanese patients with diabetes mellitus (176 males and 134 females). The relationships between plasma HCII activities and those DKD urine biomarkers were statistically evaluated. In addition, the relationship between plasma HCII activities and annual uACR changes was statistically evaluated for 201/310 patients (115 males and 86 females). RESULTS The mean plasma HCII activity of all participants was 93.8 ± 17.7%. Multivariate-regression analysis including confounding factors showed that plasma HCII activity independently contributed to the suppression of the uACR and log-transformed uACR values (P = 0.036 and P = 0.006, respectively) but not uL-FABPCR (P = 0.541). In addition, plasma HCII activity significantly and inversely correlated with annual uACR and log-transformed uACR increments after adjusting for confounding factors (P = 0.001 and P = 0.014, respectively). CONCLUSIONS The plasma HCII activity was inversely and specifically associated with glomerular injury in patients with diabetes. The results suggest that HCII can serve as a novel predictive factor for early-stage DKD development, as represented by albuminuria.
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Affiliation(s)
- Tomoyo Hara
- Department of Hematology, Endocrinology and MetabolismTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Ryoko Uemoto
- Department of Community Medicine and Medical ScienceTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Akiko Sekine
- Department of Community Medicine and Medical ScienceTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Yukari Mitsui
- Department of Hematology, Endocrinology and MetabolismTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Shiho Masuda
- Department of Hematology, Endocrinology and MetabolismTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Kiyoe Kurahashi
- Department of Hematology, Endocrinology and MetabolismTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Sumiko Yoshida
- Department of Hematology, Endocrinology and MetabolismTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Toshiki Otoda
- Department of Community Medicine and Medical ScienceTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Tomoyuki Yuasa
- Department of Community Medicine and Medical ScienceTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Akio Kuroda
- Diabetes Therapeutics and Research CenterInstitute of Advanced Medical SciencesTokushima UniversityTokushimaJapan
| | - Yasumasa Ikeda
- Department of PharmacologyTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Itsuro Endo
- Department of Bioregulatory SciencesTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Soichi Honda
- Minami Municipal National Insurance HospitalMinami‐choJapan
| | - Katsuhiko Yoshimoto
- Department of Medical PharmacologyTokushima University Graduate School of Biomedical SciencesTokushimaJapan
- Kondo Naika HospitalTokushimaJapan
| | | | | | - Toshio Matsumoto
- Fujii Memorial Institute of Medical SciencesTokushima UniversityTokushimaJapan
| | - Munehide Matsuhisa
- Diabetes Therapeutics and Research CenterInstitute of Advanced Medical SciencesTokushima UniversityTokushimaJapan
| | - Masahiro Abe
- Department of Hematology, Endocrinology and MetabolismTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Ken‐ichi Aihara
- Department of Community Medicine and Medical ScienceTokushima University Graduate School of Biomedical SciencesTokushimaJapan
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20
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Urinary neutrophil gelatinase-associated lipocalin: Acute kidney injury in liver cirrhosis. Clin Chim Acta 2021; 523:339-347. [PMID: 34666028 DOI: 10.1016/j.cca.2021.10.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 10/01/2021] [Accepted: 10/13/2021] [Indexed: 11/23/2022]
Abstract
Acute kidney injury (AKI) in liver cirrhosis is associated with poor clinical outcomes including an increased long and short-term mortality. The common type of AKI observed in patients with cirrhosis are prerenal AKI (PRA), hepatorenal syndrome (HRS) and acute tubular necrosis (ATN). Despite the growing knowledge and uniform definition for the diagnosis of AKI, there are several challenges including, early diagnosis and management. Precisely differentiating the type of AKI is critical, as therapies differ significantly. In this review, we summarize AKI in liver cirrhosis, their definition, pathophysiology and deficiencies of using the existing biomarker, serum creatinine. We outline the current clinical evidence on the novel biomarker urinary neutrophil gelatinase-associated lipocalin (uNGAL) and its potential role as a biomarker in the early detection, differentiation and prognostication of AKI. This review also briefly talks about other forthcoming biomarkers which hold promise in the management of AKI in liver cirrhosis.
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21
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Kawakami R, Matsui M, Konno A, Kaneko R, Shrestha S, Shrestha S, Sunaga H, Hanaoka H, Goto S, Hosojima M, Kabasawa H, Obokata M, Koitabashi N, Matsui H, Sasaki T, Saito A, Yanagita M, Hirai H, Kurabayashi M, Iso T. Urinary FABP1 is a biomarker for impaired proximal tubular protein reabsorption and is synergistically enhanced by concurrent liver injury. J Pathol 2021; 255:362-373. [PMID: 34370295 PMCID: PMC9292749 DOI: 10.1002/path.5775] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 07/28/2021] [Accepted: 08/04/2021] [Indexed: 11/09/2022]
Abstract
Urinary fatty acid binding protein 1 (FABP1, also known as liver‐type FABP) has been implicated as a biomarker of acute kidney injury (AKI) in humans. However, the precise biological mechanisms underlying its elevation remain elusive. Here, we show that urinary FABP1 primarily reflects impaired protein reabsorption in proximal tubule epithelial cells (PTECs). Bilateral nephrectomy resulted in a marked increase in serum FABP1 levels, suggesting that the kidney is an essential organ for removing serum FABP1. Injected recombinant FABP1 was filtered through the glomeruli and robustly reabsorbed via the apical membrane of PTECs. Urinary FABP1 was significantly elevated in mice devoid of megalin, a giant endocytic receptor for protein reabsorption. Elevation of urinary FABP1 was also observed in patients with Dent disease, a rare genetic disease characterized by defective megalin function in PTECs. Urinary FABP1 levels were exponentially increased following acetaminophen overdose, with both nephrotoxicity and hepatotoxicity observed. FABP1‐deficient mice with liver‐specific overexpression of FABP1 showed a massive increase in urinary FABP1 levels upon acetaminophen injection, indicating that urinary FABP1 is liver‐derived. Lastly, we employed transgenic mice expressing diphtheria toxin receptor (DT‐R) either in a hepatocyte‐ or in a PTEC‐specific manner, or both. Upon administration of diphtheria toxin (DT), massive excretion of urinary FABP1 was induced in mice with both kidney and liver injury, while mice with either injury type showed marginal excretion. Collectively, our data demonstrated that intact PTECs have a considerable capacity to reabsorb liver‐derived FABP1 through a megalin‐mediated mechanism. Thus, urinary FABP1, which is synergistically enhanced by concurrent liver injury, is a biomarker for impaired protein reabsorption in AKI. These findings address the use of urinary FABP1 as a biomarker of histologically injured PTECs that secrete FABP1 into primary urine, and suggest the use of this biomarker to simultaneously monitor impaired tubular reabsorption and liver function. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Ryo Kawakami
- Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Miki Matsui
- Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Ayumu Konno
- Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Japan.,Viral Vector Core, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Japan
| | - Ryosuke Kaneko
- Bioresource Center, Gunma University Graduate School of Medicine, Maebashi, Japan.,KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan
| | - Shreya Shrestha
- Department of Nephrology and Rheumatology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Suman Shrestha
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Hiroaki Sunaga
- Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.,Center for Liberal Arts and Sciences, Ashikaga University, Ashikaga, Japan
| | - Hirofumi Hanaoka
- Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Sawako Goto
- Department of Applied Molecular Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Michihiro Hosojima
- Department of Clinical Nutrition Science, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Hideyuki Kabasawa
- Department of Clinical Nutrition Science, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Masaru Obokata
- Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Norimichi Koitabashi
- Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Hiroki Matsui
- Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Japan
| | - Tsutomu Sasaki
- Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan
| | - Akihiko Saito
- Department of Applied Molecular Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Motoko Yanagita
- Department of Nephrology, Graduate School of Medicine, Kyoto, Japan.,Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan
| | - Hirokazu Hirai
- Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Japan.,Viral Vector Core, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Japan
| | - Masahiko Kurabayashi
- Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Tatsuya Iso
- Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.,Department of Medical Technology and Clinical Engineering, Faculty of Medical Technology and Clinical Engineering, Gunma University of Health and Welfare, Maebashi, Japan
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22
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Rosato E, Bonelli M, Locatelli M, de Grazia U, Tartaglia A, Savini F, D’Ovidio C. Forensic Biochemical Markers to Evaluate the Agonal Period: A Literature Review. Molecules 2021; 26:3259. [PMID: 34071519 PMCID: PMC8198460 DOI: 10.3390/molecules26113259] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 05/17/2021] [Accepted: 05/26/2021] [Indexed: 11/16/2022] Open
Abstract
Currently, forensic research is multidisciplinary with new methods and parameters useful to define the cause and time of death as well as survival/agony times. The identification of biochemical markers able to estimate agonal period has been studied by many forensic researchers. It is known that the estimation of agonal time in different types of death is not always easy, hence our interest in literature's data. The studies analyzed in this review confirm the important role of thanatobiochemistry for the estimation of survival times. Regardless of the death cause, the survival/agony time between the primary event and death influences markers concentrations in biological samples (e.g., blood, urine, cerebrospinal fluid). Different biomarkers can be used for qualitative evaluations in deaths with short and long agony (e.g., C-reactive protein, ferritin, GFAP, etc.). Instead, the quantitative interpretation showed limits due to the lack of reference cut-offs. Thanatobiochemistry is a useful tool to confirm what emerged from autopsies findings (macroscopic and histological analysis), but further studies are desirable to confirm the evidence emerging from our review of the literature.
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Affiliation(s)
- Enrica Rosato
- Department of Pharmacy, University of Chieti-Pescara “G. d’Annunzio”, Via dei Vestini 31, 66100 Chieti, Italy; (E.R.); (M.L.); (A.T.)
| | - Martina Bonelli
- Section of Legal Medicine, Center for Advanced Studies and Technology (CAST), Department of Medicine and Aging Sciences, University “G. d’Annunzio” of Chieti-Pescara, Via Polacchi, 66100 Chieti, Italy;
| | - Marcello Locatelli
- Department of Pharmacy, University of Chieti-Pescara “G. d’Annunzio”, Via dei Vestini 31, 66100 Chieti, Italy; (E.R.); (M.L.); (A.T.)
| | - Ugo de Grazia
- Laboratory of Neurological Biochemistry and Neuropharmacology, IRCCS Neurological Institute Foundation Carlo Besta, Via Celoria 11, 20133 Milan, Italy;
| | - Angela Tartaglia
- Department of Pharmacy, University of Chieti-Pescara “G. d’Annunzio”, Via dei Vestini 31, 66100 Chieti, Italy; (E.R.); (M.L.); (A.T.)
| | - Fabio Savini
- Pharmatoxicology Laboratory-Hospital “Santo Spirito”, Via Fonte Romana 8, 65124 Pescara, Italy;
| | - Cristian D’Ovidio
- Section of Legal Medicine, Center for Advanced Studies and Technology (CAST), Department of Medicine and Aging Sciences, University “G. d’Annunzio” of Chieti-Pescara, Via Polacchi, 66100 Chieti, Italy;
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23
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Zdziechowska M, Gluba-Brzózka A, Franczyk B, Rysz J. Biochemical Markers in the Prediction of Contrast-induced Acute Kidney Injury. Curr Med Chem 2021; 28:1234-1250. [PMID: 32357810 DOI: 10.2174/0929867327666200502015749] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 03/21/2020] [Accepted: 03/29/2020] [Indexed: 11/22/2022]
Abstract
For many years clinicians have been searching for "kidney troponin"- a simple diagnostic tool to assess the risk of acute kidney injury (AKI). Recently, the rise in the variety of contrast-related procedures (contrast computed tomography (CT), percutaneous coronary intervention (PCI) and angiography) has resulted in the increased number of contrast-induced acute kidney injuries (CI-AKI). CIAKI remains an important cause of overall mortality, prolonged hospitalisation and it increases the total costs of therapy. The consequences of kidney dysfunction affect the quality of life and they may lead to disability as well. Despite extensive worldwide research, there are no sensitive and reliable methods of CI-AKI prediction. Kidney Injury Molecule 1 (KIM-1) and Neutrophil Gelatinase Lipocalin (NGAL) have been considered as kidney-specific molecules. High concentrations of these substances before the implementation of contrast-related procedures have been suggested to enable the estimation of kidney vulnerability to CI-AKI and they seem to have the predictive potential for cardiovascular events and overall mortality. According to other authors, routine determination of known inflammation factors (e.g., CRP, WBC, and neutrophil count) may be helpful in the prediction of CIAKI. However, the results of clinical trials provide contrasting results. The pathomechanism of contrast- induced nephropathy remains unclear. Due to its prevalence, the evaluation of the risk of acute kidney injury remains a serious problem to be solved. This paper reviews pathophysiology and suggested optimal markers facilitating the prediction of contrast-induced acute kidney injury.
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Affiliation(s)
- Magdalena Zdziechowska
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz, Poland
| | - Anna Gluba-Brzózka
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz, Poland
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24
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Geng J, Qiu Y, Qin Z, Su B. The value of kidney injury molecule 1 in predicting acute kidney injury in adult patients: a systematic review and Bayesian meta-analysis. J Transl Med 2021; 19:105. [PMID: 33712052 PMCID: PMC7953563 DOI: 10.1186/s12967-021-02776-8] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 03/05/2021] [Indexed: 02/08/2023] Open
Abstract
Introduction The aim of the study was to systematically review relevant studies to evaluate the diagnostic value of urinary kidney injury molecule 1 (uKIM-1) for acute kidney injury (AKI) in adults. Method We searched PubMed and Embase for literature published up to November 1st, 2019 and used the Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. Then, we extracted useful information from each eligible study and pooled sensitivity, specificity, and area under the curve (AUC) values. Results A total of 14 studies with 3300 patients were included. The estimated sensitivity of urinary KIM-1 (uKIM-1) in the diagnosis of AKI was 0.74 (95% CrI 0.62–0.84), and the specificity was 0.84 (95% CrI, 0.76–0.90). The pooled diagnostic odds ratio (DOR) was 15.22 (95% CrI, 6.74–42.20), the RD was 0.55 (95% CrI 0.43–0.70), and the AUC of uKIM-1 in diagnosing AKI was 0.62 (95% CrI 0.41–0.76). The results of the subgroup analysis showed the influence of different factors. Conclusion Urinary KIM-1 is a good predictor for AKI in adult patients with relatively high sensitivity and specificity. However, further research and clinical trials are still needed to confirm whether and how uKIM-1 can be commonly used in clinical diagnosis.
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Affiliation(s)
- Jiwen Geng
- Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yuxuan Qiu
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Zheng Qin
- Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Baihai Su
- Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China.
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25
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Zhu J, Zeng C, Zhang L, Shu S, Liu Y, Chen G, Liu H, Liu Y, Dong Z. Red Blood Cell Distribution Width and Neutrophil-to-Lymphocyte Ratio in Predicting Adverse Outcomes of Acute Kidney Injury in Hospitalized Patients. KIDNEY DISEASES 2021; 6:371-381. [PMID: 33490117 DOI: 10.1159/000507859] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Accepted: 04/08/2020] [Indexed: 12/18/2022]
Abstract
Background Acute kidney injury (AKI) is a common clinical condition with high morbidity and mortality. Early risk stratification by identifying patients at risk for death or dialysis requirement has important therapeutic implications for timely interventions. Objective The aim of this study was to examine the association of routine blood test parameters, specifically red blood cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR), with the AKI patient outcomes. Methods All adult patients hospitalized from January 1, 2016, to June 30, 2016, in the Second Xiangya Hospital of Central South University were surveyed. Demographic characteristics, laboratory measurements, comorbidities, and outcomes of a total of 1,188 adult AKI patients were analyzed. Results The incidence of AKI was 1.8% (1,188/65,329). The all-cause mortality was 16.0% (190/1,188). The multivariable relative risk of AKI mortality comparing high RDW with low RDW was 1.84 and the risk comparing high NLR with low NLR was 2.54. RDW and NLR combination showed additive values in stratifying high-risk patients, and the predictive power was comparable to the use of serum creatinine for staging AKI. In subgroup analyses, high RDW predicted prerenal AKI mortality better than intrinsic AKI. High RDW and NLR also independently predicted renal replacement therapy (RRT) requirement in AKI patients. In contrast, WBC count and platelet-to-lymphocyte ratio did not show obvious correlations with death and RRT requirement in AKI patients. Conclusion The results support the potential usefulness of RDW and NLR in risk stratification of AKI patients, providing additional prognostic information for treatment and supportive care.
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Affiliation(s)
- Jiefu Zhu
- Department of Nephrology, The Second Xiangya Hospital at Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, China.,Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, Georgia, USA
| | - Cong Zeng
- Department of Nephrology, The Third Hospital of Changsha, Changsha, China
| | - Lei Zhang
- Department of Nephrology, The Second Xiangya Hospital at Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, China
| | - Shaoqun Shu
- Department of Nephrology, The Second Xiangya Hospital at Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, China
| | - Yinghong Liu
- Department of Nephrology, The Second Xiangya Hospital at Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, China
| | - Guochun Chen
- Department of Nephrology, The Second Xiangya Hospital at Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, China
| | - Hong Liu
- Department of Nephrology, The Second Xiangya Hospital at Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, China
| | - Yu Liu
- Department of Nephrology, The Second Xiangya Hospital at Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, China
| | - Zheng Dong
- Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, Georgia, USA
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26
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Karaman E, Ariman I, Ozden S. Responses of oxidative stress and inflammatory cytokines after zearalenone exposure in human kidney cells. WORLD MYCOTOXIN J 2020. [DOI: 10.3920/wmj2019.2512] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Zearalenone is a mycotoxin widely found worldwide that is produced by several fungal species. Due to its similarity to estradiol, it has been shown to have toxic effects on the reproductive system. Although various animal studies have been conducted to investigate the toxic effects of zearalenone, the mechanisms of toxicity have not been fully elucidated. The aim of the study was to investigate the dose-dependent toxic effects of zearalenone exposure in human kidney cells. The half-maximal inhibitory concentration values of zearalenone in HK-2 cells were found to be 133.42 and 101.74 µM in MTT- and NRU-tests, respectively. Zearalenone exposure at concentrations of 1, 10 and 50 µM decreased cell proliferation by 2.1, 11.07 and 24.34%, respectively. Reactive oxygen species levels increased significantly in a dose-dependent manner. A significant increase was observed in the expressions of MGMT, α-GST, Hsp70 and HO-1 genes, which are associated with oxidative damage, while a significant decrease in L-Fabp gene expression was observed. Moreover, zearalenone increased gene expression of inflammatory cytokines, such as IL-6, IL-8, TNFα and MAPK8. Significant increases were observed at the level of global DNA methylation and expression of DNMT1 in all exposure groups. These results indicate that changes in DNA methylation and oxidative damage may play an important role in the toxicity of zearalenone.
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Affiliation(s)
- E.F. Karaman
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, 34116-Beyazit, Istanbul, Turkey
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Biruni University, 34010-Topkapi, Istanbul, Turkey
| | - I. Ariman
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, 34116-Beyazit, Istanbul, Turkey
| | - S. Ozden
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, 34116-Beyazit, Istanbul, Turkey
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27
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Tsai YL, Liu CW, Huang SF, Yang YY, Lin MW, Huang CC, Li TH, Huang YH, Hou MC, Lin HC. Urinary fatty acid and retinol binding protein-4 predict CKD progression in severe NAFLD patients with hypertension: 4-year study with clinical and experimental approaches. Medicine (Baltimore) 2020; 99:e18626. [PMID: 31914044 PMCID: PMC6959901 DOI: 10.1097/md.0000000000018626] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Detection of the chronic kidney disease (CKD) progression can begin early intervention to improve the prognosis of severe non-alcoholic fatty liver disease (NAFLD). This bi-directional cross-sectional study evaluates the roles of fatty acid-binding protein (FABP) and retinol binding protein (RBP4), which are produced from inflamed liver, adipose tissue and immune cells, for the prediction of CKD progression in severe NAFLD. Ninety severe NAFLD patients with hypertension and proteinuria (NAFLDHTN) were enrolled and divided into CKD (n = 39) and non-CKD groups (n = 51). Among 39 NAFLDHTN patients, 18 cases were categorized as CKD progression group. In comparison with CKD stable group (n = 21), the positive correlation between fold change values of hepatic fibrotic score (KPa), urinary FABP4 or urinary RBP4 versus severity of albuminuria were noted among CKD progression group. On multivariate analysis, high body mass index (BMI, >25 kg/m), high hepatic fibrosis score (>9.5 KPa), high urinary level of vascular cell adhesion molecule-1 (VCAM-1, >2239 μg/g cr), high urinary level of FABP4 (>115 ng/g cr) and high urinary level of RBP4 (>33.5 mg/g cr) are 5 independent predictors for progressive CKD during 24 months of follow-up. Synergetic effect was noted among these 5 risk factors for the prediction of CKD progression in NAFLDHTN patients. The in vitro experiments revealed that both FABP4 and RBP4 directly enhanced albumin-induced ER stress and apoptosis of human renal tubular epithelial cell line HK-2 cells and human podocytes cell lines. Through clinical and experimental approaches, this study revealed new 5 synergetic predictors including high BMI, hepatic fibrosis score, urinary level of VCAM-1, urinary level of FABP4 and RBP4, for the CKD progression in severe NAFLD patients with hypertension and proteinuria.
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Affiliation(s)
- Yu-Lien Tsai
- Department of Medicine
- National Yang-Ming University School of Medicine, Taipei
| | - Chih-Wei Liu
- Division of Allergy and Immunology
- Department of Medicine
- Institute of Clinical Medicine, Taipei Veterans General Hospital
- National Yang-Ming University School of Medicine, Taipei
| | - Shiang-Fen Huang
- Division of Infection
- Department of Medicine
- Institute of Clinical Medicine, Taipei Veterans General Hospital
- National Yang-Ming University School of Medicine, Taipei
| | - Ying-Ying Yang
- Division of Gastroenterology and Hepatology
- Division of General Medicine
- Institute of Clinical Medicine, Taipei Veterans General Hospital
- National Yang-Ming University School of Medicine, Taipei
- Division of clinical skills training center, Department of medical education, Taipei, Taiwan
| | - Ming-Wei Lin
- Division of Preventive Medicine, Institute of public Health
- National Yang-Ming University School of Medicine, Taipei
| | - Chia-Chang Huang
- Department of Medicine
- National Yang-Ming University School of Medicine, Taipei
| | - Tzu-Hao Li
- Division of Allergy and Immunology
- Institute of Clinical Medicine, Taipei Veterans General Hospital
- National Yang-Ming University School of Medicine, Taipei
- Chia-Yi Branch of Taichung Veterans General Hospital, Chiayi
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology
- Department of Medicine
- Institute of Clinical Medicine, Taipei Veterans General Hospital
- National Yang-Ming University School of Medicine, Taipei
| | - Ming-Chih Hou
- Department of Medicine
- National Yang-Ming University School of Medicine, Taipei
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology
- National Yang-Ming University School of Medicine, Taipei
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28
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Dhama K, Latheef SK, Dadar M, Samad HA, Munjal A, Khandia R, Karthik K, Tiwari R, Yatoo MI, Bhatt P, Chakraborty S, Singh KP, Iqbal HMN, Chaicumpa W, Joshi SK. Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values. Front Mol Biosci 2019; 6:91. [PMID: 31750312 PMCID: PMC6843074 DOI: 10.3389/fmolb.2019.00091] [Citation(s) in RCA: 154] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Accepted: 09/11/2019] [Indexed: 02/05/2023] Open
Abstract
Various internal and external factors negatively affect the homeostatic equilibrium of organisms at the molecular to the whole-body level, inducing the so-called state of stress. Stress affects an organism's welfare status and induces energy-consuming mechanisms to combat the subsequent ill effects; thus, the individual may be immunocompromised, making them vulnerable to pathogens. The information presented here has been extensively reviewed, compiled, and analyzed from authenticated published resources available on Medline, PubMed, PubMed Central, Science Direct, and other scientific databases. Stress levels can be monitored by the quantitative and qualitative measurement of biomarkers. Potential markers of stress include thermal stress markers, such as heat shock proteins (HSPs), innate immune markers, such as Acute Phase Proteins (APPs), oxidative stress markers, and chemical secretions in the saliva and urine. In addition, stress biomarkers also play critical roles in the prognosis of stress-related diseases and disorders, and therapy guidance. Moreover, different components have been identified as potent mediators of cardiovascular, central nervous system, hepatic, and nephrological disorders, which can also be employed to evaluate these conditions precisely, but with stringent validation and specificity. Considerable scientific advances have been made in the detection, quantitation, and application of these biomarkers. The present review describes the current progress of identifying biomarkers, their prognostic, and therapeutic values.
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Affiliation(s)
- Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Shyma K. Latheef
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Maryam Dadar
- Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj, Iran
| | - Hari Abdul Samad
- Division of Physiology and Climatology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Ashok Munjal
- Department of Genetics, Barkatullah University, Bhopal, India
| | - Rekha Khandia
- Department of Genetics, Barkatullah University, Bhopal, India
| | - Kumaragurubaran Karthik
- Central University Laboratory, Tamil Nadu Veterinary and Animal Sciences University, Chennai, India
| | - Ruchi Tiwari
- Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, UP Pandit Deen Dayal Upadhayay Pashu Chikitsa Vigyan Vishwavidyalay Evum Go-Anusandhan Sansthan, Mathura, India
| | - Mohd. Iqbal Yatoo
- Division of Veterinary Clinical Complex, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, India
| | - Prakash Bhatt
- Teaching Veterinary Clinical Complex, College of Veterinary and Animal Sciences, Govind Ballabh Pant University of Agriculture and Technology, Pantnagar, India
| | - Sandip Chakraborty
- Department of Veterinary Microbiology, College of Veterinary Sciences and Animal Husbandry, Agartala, India
| | - Karam Pal Singh
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Hafiz M. N. Iqbal
- Tecnologico de Monterrey, School of Engineering and Sciences, Monterrey, Mexico
| | - Wanpen Chaicumpa
- Department of Parasitology, Faculty of Medicine, Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sunil Kumar Joshi
- Division of Hematology, Oncology and Bone Marrow Transplantation, Department of Microbiology & Immunology, Department of Pediatrics, University of Miami School of Medicine, Miami, FL, United States
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29
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Dhama K, Latheef SK, Dadar M, Samad HA, Munjal A, Khandia R, Karthik K, Tiwari R, Yatoo MI, Bhatt P, Chakraborty S, Singh KP, Iqbal HMN, Chaicumpa W, Joshi SK. Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values. Front Mol Biosci 2019. [PMID: 31750312 DOI: 10.3389/fmolb.2019.0009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Various internal and external factors negatively affect the homeostatic equilibrium of organisms at the molecular to the whole-body level, inducing the so-called state of stress. Stress affects an organism's welfare status and induces energy-consuming mechanisms to combat the subsequent ill effects; thus, the individual may be immunocompromised, making them vulnerable to pathogens. The information presented here has been extensively reviewed, compiled, and analyzed from authenticated published resources available on Medline, PubMed, PubMed Central, Science Direct, and other scientific databases. Stress levels can be monitored by the quantitative and qualitative measurement of biomarkers. Potential markers of stress include thermal stress markers, such as heat shock proteins (HSPs), innate immune markers, such as Acute Phase Proteins (APPs), oxidative stress markers, and chemical secretions in the saliva and urine. In addition, stress biomarkers also play critical roles in the prognosis of stress-related diseases and disorders, and therapy guidance. Moreover, different components have been identified as potent mediators of cardiovascular, central nervous system, hepatic, and nephrological disorders, which can also be employed to evaluate these conditions precisely, but with stringent validation and specificity. Considerable scientific advances have been made in the detection, quantitation, and application of these biomarkers. The present review describes the current progress of identifying biomarkers, their prognostic, and therapeutic values.
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Affiliation(s)
- Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Shyma K Latheef
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Maryam Dadar
- Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj, Iran
| | - Hari Abdul Samad
- Division of Physiology and Climatology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Ashok Munjal
- Department of Genetics, Barkatullah University, Bhopal, India
| | - Rekha Khandia
- Department of Genetics, Barkatullah University, Bhopal, India
| | - Kumaragurubaran Karthik
- Central University Laboratory, Tamil Nadu Veterinary and Animal Sciences University, Chennai, India
| | - Ruchi Tiwari
- Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, UP Pandit Deen Dayal Upadhayay Pashu Chikitsa Vigyan Vishwavidyalay Evum Go-Anusandhan Sansthan, Mathura, India
| | - Mohd Iqbal Yatoo
- Division of Veterinary Clinical Complex, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, India
| | - Prakash Bhatt
- Teaching Veterinary Clinical Complex, College of Veterinary and Animal Sciences, Govind Ballabh Pant University of Agriculture and Technology, Pantnagar, India
| | - Sandip Chakraborty
- Department of Veterinary Microbiology, College of Veterinary Sciences and Animal Husbandry, Agartala, India
| | - Karam Pal Singh
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Hafiz M N Iqbal
- Tecnologico de Monterrey, School of Engineering and Sciences, Monterrey, Mexico
| | - Wanpen Chaicumpa
- Department of Parasitology, Faculty of Medicine, Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sunil Kumar Joshi
- Division of Hematology, Oncology and Bone Marrow Transplantation, Department of Microbiology & Immunology, Department of Pediatrics, University of Miami School of Medicine, Miami, FL, United States
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30
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Tajima S, Fu R, Shigematsu T, Noguchi H, Kaku K, Tsuchimoto A, Okabe Y, Masuda S. Urinary Human Epididymis Secretory Protein 4 as a Useful Biomarker for Subclinical Acute Rejection Three Months after Kidney Transplantation. Int J Mol Sci 2019; 20:ijms20194699. [PMID: 31546745 PMCID: PMC6801851 DOI: 10.3390/ijms20194699] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 09/20/2019] [Accepted: 09/20/2019] [Indexed: 02/07/2023] Open
Abstract
Kidney transplantation is the treatment of choice for patients with advanced chronic kidney disease (CKD) and end stage renal disease (ESRD). However, acute rejection (AR) is a common complication in kidney transplantation and is associated with reduced graft survival. Current diagnosis of AR relies mainly on clinical monitoring including serum creatinine, proteinuria, and confirmation by histopathologic assessment in the biopsy specimen of graft kidney. Although an early protocol biopsy is indispensable for depicting the severity of pathologic lesions in subclinical acute rejection (subAR), it is not acceptable in some cases and cannot be performed because of its invasive nature. Therefore, we examined the detection of noninvasive biomarkers that are closely related to the pathology of subAR in protocol biopsies three months after kidney transplantation. In this study, the urinary level of microtubule-associated protein 1 light chain 3 (LC3), monocyte chemotactic protein-1 (MCP-1), liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and human epididymis secretory protein 4 (HE4) were measured three months after kidney transplantation. Urine samples of 80 patients undergoing kidney transplantation between August 2014 to September 2016, were prospectively collected after three months. SubAR was observed in 11 patients (13.8%) in protocol biopsy. The urinary levels of LC3, MCP-1, NGAL, and HE4 were significantly higher in patients with subAR than in those without, while those of L-FABP did not differ between the two groups. Multivariate regression models, receiver-operating characteristics (ROC), and areas under ROC curves (AUC) were used to identify predicted values of subAR. Urinary HE4 levels were able to better identify subAR (AUC = 0.808) than the other four urinary biomarkers. In conclusion, urinary HE4 is increased in kidney transplant recipients of subAR three months after kidney transplantation, suggesting that HE4 has the potential to be used as a novel clinical biomarker for predicting subAR.
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Affiliation(s)
- Soichiro Tajima
- Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
| | - Rao Fu
- Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
| | - Tomohiro Shigematsu
- Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
- Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
| | - Hiroshi Noguchi
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
| | - Keizo Kaku
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
| | - Akihiro Tsuchimoto
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
| | - Yasuhiro Okabe
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
| | - Satohiro Masuda
- Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
- Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
- Department of Pharmacy, International University of Health and Welfare Narita Hospital, Minami-Aoyama, Minato-ku, Tokyo 107-0062, Japan.
- Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, International University of Health and Welfare Narita Hospital, Minami-Aoyama, Minato-ku, Tokyo 107-0062, Japan.
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Abstract
INTRODUCTION The term cardiorenal syndrome (CRS) describes the progressive pathology and interactions that develop upon heart and kidney failure. The definition of CRS is not firmly established and has evolved gradually during the last decade. The main clinical challenges associated with CRS are the lack of tools for early disease diagnosis and the inability to predict the development of cardiorenal pathophysiology. Currently several biomarkers have been proposed for improving CRS patient management. However, validation studies are needed to implement these initial findings to the clinical setting. Areas covered: In this review the database PubMed was used for a literature search on the definition and classification of CRS as well as biomarkers for CRS diagnosis and prognosis. Expert opinion: A universally acceptable classification system for CRS is not available. Thus, acquiring mechanistic insights relative to the pathophysiology of the disease is challenging. Reported biomarkers include well-established markers for heart/renal dysfunction and inflammation. Some proteins expressed in both organs have also been associated with CRS, yet their link to disease pathophysiology and organ cross-talk is missing. Establishing the link between deregulated molecular pathways and CRS phenotypes is required to define biological relevance of existing findings and ultimately biology-driven markers and targets.
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Affiliation(s)
- Eleni Petra
- a Biotechnology Division, Biomedical Research Foundation , Academy of Athens (BRFAA) , Athens , Greece
| | - Jerome Zoidakis
- a Biotechnology Division, Biomedical Research Foundation , Academy of Athens (BRFAA) , Athens , Greece
| | - Antonia Vlahou
- a Biotechnology Division, Biomedical Research Foundation , Academy of Athens (BRFAA) , Athens , Greece
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Nielsen MB, Krogstrup NV, Nieuwenhuijs-Moeke GJ, Oltean M, Dor FJMF, Jespersen B, Birn H. P-NGAL Day 1 predicts early but not one year graft function following deceased donor kidney transplantation - The CONTEXT study. PLoS One 2019; 14:e0212676. [PMID: 30817778 PMCID: PMC6394926 DOI: 10.1371/journal.pone.0212676] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 01/31/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Early markers to predict delayed kidney graft function (DGF) may support clinical management. We studied the ability of four biomarkers (neutrophil gelatinase associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), cystatin C, and YKL-40) to predict DGF after deceased donor transplantation, and their association with early graft function and GFR at three and twelve months. METHODS 225 deceased donor kidney transplant recipients were included. Biomarkers were measured using automated assays or ELISA. We calculated their ability to predict the need for dialysis post-transplant and correlated with the estimated time to a 50% reduction in plasma creatinine (tCr50), measured glomerular filtration rate (mGFR) and estimated GFR (eGFR). RESULTS All biomarkers measured at Day 1, except urinary L-FABP, significantly correlated with tCr50 and mGFR at Day 5. Plasma NGAL at Day 1 and a timed urine output predicted DGF (AUC = 0.91 and AUC 0.98). Nil or only weak correlations were identified between early biomarker levels and mGFR or eGFR at three or twelve months. CONCLUSION High plasma NGAL at Day 1 predicts DGF and is associated with initial graft function, but may not prove better than P-creatinine or a timed urine output. Early biomarker levels do not correlate with one-year graft function. TRIAL REGISTRATION ClinicalTrials.gov NCT01395719.
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Affiliation(s)
- Marie B. Nielsen
- Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Nicoline V. Krogstrup
- Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | | | - Mihai Oltean
- The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Frank J. M. F. Dor
- Division of HPB & Transplant Surgery, Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College, London, United Kingdom
| | - Bente Jespersen
- Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Henrik Birn
- Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
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Teo SH, Endre ZH. Biomarkers in acute kidney injury (AKI). Best Pract Res Clin Anaesthesiol 2018; 31:331-344. [PMID: 29248140 DOI: 10.1016/j.bpa.2017.10.003] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 10/25/2017] [Indexed: 12/14/2022]
Abstract
Acute kidney injury is common in critically ill patients and portends a significant impact on mortality, progressive chronic kidney disease, and cardiovascular disease and mortality. Though most physicians alter therapy depending on changes in serum creatinine, this often represents delayed intervention. Various AKI biomarkers have been discovered and validated to improve timely detection, differentiation and stratification into risk groups for progressive renal decline, need for renal replacement therapy or death. This chapter will review AKI biomarkers validated over the past decade. We also describe the clinical performance of the biomarkers. We suggest that using AKI biomarkers to complement serum creatinine (or cystatin C) and urine output will better integrate patient care through earlier recognition and clinical outcome prediction after AKI.
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Affiliation(s)
- Su Hooi Teo
- Department of Nephrology, Singapore General Hospital, Singapore
| | - Zoltán Huba Endre
- Department of Nephrology, Prince of Wales Hospital, High Street, Randwick, Sydney, 2031, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, Australia; Department of Medicine, University of Otago-Christchurch; Christchurch, New Zealand; School of Medicine, University of Queensland, Brisbane, Australia.
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Sugiyama M. Measurement of urinary biomarkers in a case of tubulointerstitial nephritis and uveitis syndrome during glucocorticoid treatment. CEN Case Rep 2018; 7:221-224. [PMID: 29761376 DOI: 10.1007/s13730-018-0330-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 04/16/2018] [Indexed: 01/22/2023] Open
Abstract
Tubulointerstitial nephritis and uveitis (TINU) is a rare syndrome in which idiopathic interstitial nephritis coexists with chronic recurrent uveitis. This syndrome often represents systemic disorders such as arthralgia, rash, prolonged fever, anaemia and ocular symptoms that require medication including glucocorticoid administration. Recently, novel urinary biomarkers, such as kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and liver-type fatty acid-binding protein, were shown to be associated with tubulointerstitial damage and were elevated in interstitial nephritis. We evaluated these urinary biomarkers in a case of TINU syndrome before and during treatment and found that their levels were elevated at onset and decreased during treatment, especially NGAL. We conclude that these urinary biomarkers are useful to evaluate and predict prognosis in interstitial nephritis.
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Affiliation(s)
- Masafumi Sugiyama
- Department of Nephrology and Rheumatology, Hashima Municipal Hospital, 3-246 Shinsei-cho, Hashima, Gifu, 501-6206, Japan.
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Wang JJ, Chi NH, Huang TM, Connolly R, Chen LW, Chueh SCJ, Kan WC, Lai CC, Wu VC, Fang JT, Chu TS, Wu KD. Urinary biomarkers predict advanced acute kidney injury after cardiovascular surgery. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2018; 22:108. [PMID: 29699579 PMCID: PMC5921971 DOI: 10.1186/s13054-018-2035-8] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Accepted: 04/09/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Acute kidney injury (AKI) after cardiovascular surgery is a serious complication. Little is known about the ability of novel biomarkers in combination with clinical risk scores for prediction of advanced AKI. METHODS In this prospectively conducted multicenter study, urine samples were collected from 149 adults at 0, 3, 6, 12 and 24 h after cardiovascular surgery. We measured urinary hemojuvelin (uHJV), kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), α-glutathione S-transferase (uα-GST) and π-glutathione S-transferase (uπ-GST). The primary outcome was advanced AKI, under the definition of Kidney Disease: Improving Global Outcomes (KDIGO) stage 2, 3 and composite outcomes were KDIGO stage 2, 3 or 90-day mortality after hospital discharge. RESULTS Patients with advanced AKI had significantly higher levels of uHJV and uKIM-1 at 3, 6 and 12 h after surgery. When normalized by urinary creatinine level, uKIM-1 in combination with uHJV at 3 h post-surgery had a high predictive ability for advanced AKI and composite outcome (AUC = 0.898 and 0.905, respectively). The combination of this biomarker panel (normalized uKIM-1, uHJV at 3 h post-operation) and Liano's score was superior in predicting advanced AKI (AUC = 0.931, category-free net reclassification improvement of 1.149, and p < 0.001). CONCLUSIONS When added to Liano's score, normalized uHJV and uKIM-1 levels at 3 h after cardiovascular surgery enhanced the identification of patients at higher risk of progression to advanced AKI and composite outcomes.
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Affiliation(s)
- Jian-Jhong Wang
- Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan.,NSARF group (National Taiwan University Hospital Study Group of ARF), Taipei, Taiwan
| | - Nai-Hsin Chi
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Tao-Min Huang
- NSARF group (National Taiwan University Hospital Study Group of ARF), Taipei, Taiwan.,Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Rory Connolly
- School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland
| | - Liang Wen Chen
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Chieh Jeff Chueh
- Cleveland Clinic Lerner College of Medicine and Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, USA
| | - Wei-Chih Kan
- Division of Nephrology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Chih-Cheng Lai
- Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
| | - Vin-Cent Wu
- NSARF group (National Taiwan University Hospital Study Group of ARF), Taipei, Taiwan. .,Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
| | - Ji-Tseng Fang
- Chang Gung University College of Medicine, Taoyuan, Taiwan.,Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan City, Taiwan
| | - Tzong-Shinn Chu
- NSARF group (National Taiwan University Hospital Study Group of ARF), Taipei, Taiwan.,Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Kwan-Dun Wu
- NSARF group (National Taiwan University Hospital Study Group of ARF), Taipei, Taiwan.,Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Identification of Urinary Activin A as a Novel Biomarker Reflecting the Severity of Acute Kidney Injury. Sci Rep 2018; 8:5176. [PMID: 29581558 PMCID: PMC5980079 DOI: 10.1038/s41598-018-23564-3] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Accepted: 03/15/2018] [Indexed: 12/19/2022] Open
Abstract
Acute kidney injury (AKI) is a common but complex condition that is associated with increased morbidity and mortality. In the present study, we examined whether urinary activin A, a member of the TGF-beta superfamily, is present in mice with ischemia-reperfusion injury and in humans with AKI, as well as its potential as a biomarker for AKI. Expression of activin A was markedly increased in ischemic mouse kidneys. In situ hybridization demonstrated that activin mRNA was expressed in tubular cells of ischemic kidneys but not of normal kidneys. Immunoreactive activin A, which was absent in normal kidneys, was detected in the cytoplasm of proximal tubular cells in ischemic kidneys. Activin A was undetectable in the urine of normal mice. In contrast, activin A was significantly increased in the urine of ischemic mice at 3 h after reperfusion. Urinary activin A levels increased according to the period of ischemia. In humans, urinary activin A was almost undetectable in healthy volunteers and in patients with pre-renal AKI, but was significantly increased in patients with renal AKI. There was no significant correlation between urinary activin A and serum activin A. Collectively, urinary activin A might be a useful biomarker reflecting the severity of AKI.
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Horie S, Oya M, Nangaku M, Yasuda Y, Komatsu Y, Yanagita M, Kitagawa Y, Kuwano H, Nishiyama H, Ishioka C, Takaishi H, Shimodaira H, Mogi A, Ando Y, Matsumoto K, Kadowaki D, Muto S. Guidelines for treatment of renal injury during cancer chemotherapy 2016. Clin Exp Nephrol 2018; 22:210-244. [PMID: 28856465 PMCID: PMC5805816 DOI: 10.1007/s10157-017-1448-z] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Shigeo Horie
- Department of Urology, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
- Department of Advanced Informatics for Genetic Disease, Juntendo University Graduate School of Medicine, Tokyo, Japan.
| | - Mototsugu Oya
- Department of Urology, Keio University School of Medicine, Tokyo, Japan
| | - Masaomi Nangaku
- Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | - Yoshinari Yasuda
- Department of CKD Initiatives/Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yasuhiro Komatsu
- Division of Nephrology, Department of Medicine, St. Luke's International Hospital, Tokyo, Japan
| | - Motoko Yanagita
- Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Hiroyuki Kuwano
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Hiroyuki Nishiyama
- Department of Urology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Chikashi Ishioka
- Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Miyagi, Japan
| | - Hiromasa Takaishi
- Keio Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Hideki Shimodaira
- Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Miyagi, Japan
| | - Akira Mogi
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Yuichi Ando
- Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Aichi, Japan
| | - Koji Matsumoto
- Division of Medical Oncology, Hyogo Cancer Center, Hyogo, Japan
| | - Daisuke Kadowaki
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
| | - Satoru Muto
- Department of Urology, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
- Department of Advanced Informatics for Genetic Disease, Juntendo University Graduate School of Medicine, Tokyo, Japan
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Abstract
OBJECTIVE Norwood palliation for patients with single ventricle heart disease is associated with a significant risk for acute kidney injury, which portends a worse prognosis. We sought to investigate the impact of hybrid stage I palliation (Hybrid) on acute kidney injury risk. DESIGN This study is a single-centre prospective case-control study of seven consecutive neonates with single ventricle undergoing Hybrid palliation. Levels of serum creatinine and four novel urinary biomarkers, namely neutrophil gelatinase-associated lipocalin, interleukin-18, liver fatty acid-binding protein, and kidney injury molecule-1, were obtained before and after palliation. Acute kidney injury was defined as a ⩾50% increase in serum creatinine within 48 hours after the procedure. Data were compared with a contemporary cohort of 12 neonates with single ventricle who underwent Norwood palliation. RESULTS Patients who underwent Hybrid were more likely to be high-risk candidates (86 versus 25%, p=0.01) compared with those who underwent Norwood. Despite similar preoperative serum creatinine levels, there was a trend towards higher levels of postoperative peak serum creatinine (0.7 [0.63, 0.94] versus 0.56 [0.47, 0.74], p=0.06) and rate of acute kidney injury (67 versus 29%, p=0.17) in the Norwood cohort. Preoperative neutrophil gelatinase-associated lipocalin (58.4 [11, 86.3] versus 6.3 [5, 16.2], p=0.07) and interleukin-18 (30.6 [9.6, 167.2] versus 6.3 [6.3, 16.4], p=0.03) levels were higher in the Hybrid cohort. Nevertheless, longitudinal mixed-effect models demonstrated Hybrid palliation to be a protective factor against increased postoperative levels of neutrophil gelatinase-associated lipocalin (estimate -1.8 [-3.0, -9.0], p<0.001) and liver fatty acid-binding protein (-49.3 [-89.7, -8.8], p=0.018). CONCLUSIONS In this single-centre case-control study, postoperative acute kidney injury risk did not differ significantly by single ventricle stage I treatment strategy; however, postoperative elevation in novel urinary biomarkers, consistent with subclinical kidney injury, was encountered in the Norwood cohort but not in the Hybrid cohort.
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39
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Wang Y, Bellomo R. Cardiac surgery-associated acute kidney injury: risk factors, pathophysiology and treatment. Nat Rev Nephrol 2017; 13:697-711. [DOI: 10.1038/nrneph.2017.119] [Citation(s) in RCA: 468] [Impact Index Per Article: 58.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Kashani K, Cheungpasitporn W, Ronco C. Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption. Clin Chem Lab Med 2017; 55:1074-1089. [PMID: 28076311 DOI: 10.1515/cclm-2016-0973] [Citation(s) in RCA: 199] [Impact Index Per Article: 24.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 10/31/2016] [Indexed: 12/11/2022]
Abstract
Acute kidney injury (AKI) is a common complication of critical illnesses and has a significant impact on outcomes, including mortality and morbidities. Unfortunately, apart from prophylactic measures, no effective treatment for this syndrome is known. Therefore, early recognition of AKI not only can provide better opportunities for preventive interventions, but also opens many gates for research and development of effective therapeutic options. Over the last few years, several new AKI biomarkers have been discovered and validated to improve early detection, differential diagnosis, and differentiation of patients into risk groups for progressive renal failure, need for renal replacement therapy (RRT), or death. These novel AKI biomarkers complement serum creatinine (SCr) and urine output, which are the standard diagnostic tools for AKI detection. In this article, we review the available literature on characteristics of promising AKI biomarkers that are currently the focus of preclinical and clinical investigations. These biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein, interleukin 18 (lL-18), insulin-like growth factor-binding protein 7, tissue inhibitor of metalloproteinase 2 (TIMP-2), calprotectin, urine angiotensinogen (AGT), and urine microRNA. We then describe the clinical performance of these biomarkers for diagnosis and prognostication. We also appraise each AKI biomarker's advantages and limitations as a tool for early AKI recognition and prediction of clinical outcomes after AKI. Finally, we review the current and future states of implementation of biomarkers in the clinical practice.
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Shirakabe A, Hata N, Kobayashi N, Okazaki H, Matsushita M, Shibata Y, Nishigoori S, Uchiyama S, Asai K, Shimizu W. Clinical Usefulness of Urinary Liver Fatty Acid-Binding Protein Excretion for Predicting Acute Kidney Injury during the First 7 Days and the Short-Term Prognosis in Acute Heart Failure Patients with Non-Chronic Kidney Disease. Cardiorenal Med 2017; 7:301-315. [PMID: 29118769 DOI: 10.1159/000477825] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 05/15/2017] [Indexed: 12/20/2022] Open
Abstract
Background The clinical significance of urinary liver fatty acid-binding protein (u-LFABP) in acute heart failure (AHF) patients remains unclear. Methods and Results The u-LFABP levels on admission of 293 AHF patients were analyzed. The patients were divided into 2 groups according to the u-LFABP quartiles (Q1, Q2, and Q3 = low u-LFABP [L] group vs. Q4 = high u-LFABP [H] group). We evaluated the diagnostic and prognostic value of u-LFABP and compared the findings between the chronic kidney disease (CKD; n = 165) and non-CKD patients (n = 128). Acute kidney injury (AKI) during the first 7 days was evaluated based on the RIFLE criteria. In the non-CKD group, the number of AKI patients during the first 7 days was significantly greater in the H group (70.0%) than in the L group (45.6%). A multivariate logistic regression model indicated that the H group (odds ratio: 3.850, 95% confidence interval [CI] 1.128-13.140) was independently associated with AKI during the first 7 days. The sensitivity and specificity of u-LFABP for predicting AKI were 63.6 and 59.7% (area under the ROC curve 0.631) at 41.9 ng/mg × cre. A Cox regression model identified the H group (hazard ratio: 13.494, 95% CI 1.512-120.415) as an independent predictor of the 60-day mortality. A Kaplan-Meier curve, including all-cause death within 60 days, showed a significantly poorer survival rate in the H group than in the L group (p = 0.036). Conclusions The u-LFABP level is an effective biomarker for predicting AKI during the first 7 days of hospitalization and an adverse outcome in AHF patients with non-CKD.
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Affiliation(s)
- Akihiro Shirakabe
- Division of Intensive Care Unit, Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan
| | - Noritake Hata
- Division of Intensive Care Unit, Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan
| | - Nobuaki Kobayashi
- Division of Intensive Care Unit, Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan
| | - Hirotake Okazaki
- Division of Intensive Care Unit, Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan
| | - Masato Matsushita
- Division of Intensive Care Unit, Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan
| | - Yusaku Shibata
- Division of Intensive Care Unit, Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan
| | - Suguru Nishigoori
- Division of Intensive Care Unit, Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan
| | - Saori Uchiyama
- Division of Intensive Care Unit, Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan
| | - Kuniya Asai
- Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
| | - Wataru Shimizu
- Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
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Shiao CC, Huang TM, Spapen HD, Honore PM, Wu VC. Optimal timing of renal replacement therapy initiation in acute kidney injury: the elephant felt by the blindmen? Crit Care 2017; 21:146. [PMID: 28629397 PMCID: PMC5477147 DOI: 10.1186/s13054-017-1713-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Renal replacement therapy (RRT) is a key component in the management of severe acute kidney injury (AKI) in critically ill patients. Many cohort studies, meta-analyses, and two recent large randomized prospective trials which evaluated the relationship between the timing of RRT initiation and patient outcome remain inconclusive due to substantial differences in study design, patient population, AKI definition, and RRT indication. A cause-specific diagnosis of AKI based on current staging criteria plus a sensitive biomarker (panel) that allows creating a homogeneous study population is definitely needed to assess the impact of early versus late initiation of RRT on patient outcome.
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Affiliation(s)
- Chih-Chung Shiao
- Division of Nephrology, Department of Internal Medicine, Saint Mary’s Hospital Luodong, No. 160 Chong-Cheng South Road, Loudong 265, Yilan, Taiwan (Republic of China)
- Saint Mary’s Junior College of Medicine, Nursing and Management, No.100, Ln. 265, Sec. 2, Sanxing Road, Sanxing Township, Yilan County, 266 Taiwan (Republic of China)
| | - Tao-Min Huang
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Zhong-Zheng District, Taipei, 100 Taiwan (Republic of China)
| | - Herbert D. Spapen
- ICU Department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, 101, Laarbeeklaan, 1090 Jette, Brussels, Belgium
| | - Patrick M. Honore
- ICU Department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, 101, Laarbeeklaan, 1090 Jette, Brussels, Belgium
| | - Vin-Cent Wu
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Zhong-Zheng District, Taipei, 100 Taiwan (Republic of China)
- NSARF, National Taiwan University Study Group on Acute Renal Failure, Taipei, Taiwan (Republic of China)
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Quantified kidney echogenicity in mice with renal ischemia reperfusion injury: evaluation as a noninvasive biomarker of acute kidney injury. Med Mol Morphol 2017; 50:161-169. [DOI: 10.1007/s00795-017-0157-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Accepted: 03/11/2017] [Indexed: 01/07/2023]
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Yap DYH, Seto WK, Fung J, Chok SH, Chan SC, Chan GCW, Yuen MF, Chan TM. Serum and urinary biomarkers that predict hepatorenal syndrome in patients with advanced cirrhosis. Dig Liver Dis 2017; 49:202-206. [PMID: 27876501 DOI: 10.1016/j.dld.2016.11.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Revised: 10/29/2016] [Accepted: 11/02/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Prediction of hepatorenal syndrome (HRS) remains difficult in advanced cirrhotic patients. AIMS To evaluate use of serum and urine biomarkers to predict HRS. METHODS We prospectively recruited Child's B or C cirrhotic patients with normal serum creatinine, and followed them for 12 weeks for the development of HRS. Serum Cystatin C (CysC), serum and urine Neutrophil Gelatinase-Associated Lipocalin (NGAL), serum and urine IL-18, serum N-acetyl-β-d glucosaminidase (NAG), urine kidney injury molecule-1 (KIM-1) and urine liver-type fatty acid binding protein (LFABP) were measured at recruitment (baseline), and their relationship with subsequent HRS investigated. RESULTS 43 patients were included. 12 (27.9%) developed HRS at 7.3±5.1 weeks from baseline. Logistic regression analysis showed that baseline urinary NGAL and urinary KIM-1 were significantly associated with the development of HRS (RR 1.007, 95% CI 1.001-1.012, p=0.014; RR 1.973, 95% CI 1.002-3.886, p=0.049). The cut-off values for NGAL and KIM-1 to predict HRS were 18.72ng/mL and 1.499ng/mL respectively (AUCs 0.84, p=0.005; and 0.78, p=0.008). CONCLUSION Urinary NGAL and KIM-1 could serve as biomarkers to predict HRS in advanced cirrhotic patients.
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Affiliation(s)
- Desmond Y H Yap
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong.
| | - Wai Kay Seto
- Division of Gastroenterology and Hepatology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - James Fung
- Division of Gastroenterology and Hepatology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Siu Ho Chok
- Division of Liver Transplantation, Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - See Ching Chan
- Division of Liver Transplantation, Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Gary C W Chan
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Man Fung Yuen
- Division of Gastroenterology and Hepatology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Tak Mao Chan
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
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Abstract
AKI is an increasingly common disorder that is strongly linked to short- and long-term morbidity and mortality. Despite a growing heterogeneity in its causes, providing a timely and certain diagnosis of AKI remains challenging. In this review, we summarize the evolution of AKI biomarker studies over the past few years, focusing on two major areas of investigation: the early detection and prognosis of AKI. We highlight some of the lessons learned in conducting AKI biomarker studies, including ongoing attempts to address the limitations of creatinine as a reference standard and the recent shift toward evaluating the prognostic potential of these markers. Lastly, we suggest current gaps in knowledge and barriers that may be hindering their incorporation into care and a full ascertainment of their value.
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Affiliation(s)
- Rakesh Malhotra
- Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, California
| | - Edward D. Siew
- Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical center, Nashville, Tennessee
- Tennessee Valley Healthcare System, Veteran's Administration Medical Center, Veterans Health Administration, Nashville, Tennessee; and
- Vanderbilt Center for Kidney Disease and Integrated Program for Acute Kidney Injury Research, Nashville, Tennessee
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Andreucci M, Faga T, Riccio E, Sabbatini M, Pisani A, Michael A. The potential use of biomarkers in predicting contrast-induced acute kidney injury. Int J Nephrol Renovasc Dis 2016; 9:205-21. [PMID: 27672338 PMCID: PMC5024777 DOI: 10.2147/ijnrd.s105124] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Contrast-induced acute kidney injury (CI-AKI) is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C), kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP). The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect.
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Affiliation(s)
- Michele Andreucci
- Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro
| | - Teresa Faga
- Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro
| | - Eleonora Riccio
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Massimo Sabbatini
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Antonio Pisani
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Ashour Michael
- Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro
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Shirakabe A, Kobayashi N, Hata N, Shinada T, Tomita K, Tsurumi M, Okazaki H, Matsushita M, Yamamoto Y, Yokoyama S, Asai K, Shimizu W. The serum heart-type fatty acid-binding protein (HFABP) levels can be used to detect the presence of acute kidney injury on admission in patients admitted to the non-surgical intensive care unit. BMC Cardiovasc Disord 2016; 16:174. [PMID: 27596162 PMCID: PMC5011936 DOI: 10.1186/s12872-016-0340-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Accepted: 06/23/2016] [Indexed: 01/12/2023] Open
Abstract
Background No cardiac biomarkers for detecting acute kidney injury (AKI) on admission in non-surgical intensive care patients have been reported. The aim of the present study is to elucidate the role of cardiac biomarkers for quickly identifying the presence of AKI on admission. Methods Data for 1183 patients who underwent the measurement of cardiac biomarkers, including the serum heart-type fatty acid-binding protein (s-HFABP) level, in the emergency department were screened, and 494 non-surgical intensive care patients were enrolled in this study. Based on the RIFLE classification, which was the ratio of the serum creatinine value recorded on admission to the baseline creatinine value, the patients were assigned to a no-AKI (n = 349) or AKI (Class R [n = 83], Class I [n = 36] and Class F [n = 26]) group on admission. We evaluated the diagnostic value of the s-H-FABP level for detecting AKI and Class I/F. The mid-term prognosis, as all-cause death within 180 days, was also evaluated. Results The s-H-FABP levels were significantly higher in the Class F (79.2 [29.9 to 200.3] ng/mL) than in the Class I (41.5 [16.7 to 71.6] ng/mL), the Class R (21.1 [10.2 to 47.9] ng/mL), and no-AKI patients (8.8 [5.4 to 17.7] ng/mL). The most predictive values for detecting AKI were Q2 (odds ratio [OR]: 3.743; 95 % confidence interval [CI]: 1.693–8.274), Q3 (OR: 9.427; 95 % CI: 4.124–21.548), and Q4 (OR: 28.000; 95 % CI: 11.245–69.720), while those for Class I/F were Q3 (OR: 5.155; 95 % CI: 1.030–25.790) and Q4 (OR: 22.978; 95 % CI: 4.814–109.668). The s-HFABP level demonstrating an optimal balance between sensitivity and specificity (70.3 and 72.8 %, respectively; area under the curve: 0.774; 95 % CI: 0.728–0.819) was 15.7 ng/mL for AKI and 20.7 ng/mL for Class I/F (71.0 and 83.1 %, respectively; area under the curve: 0.818; 95 % CI: 0.763–0.873). The prognosis was significantly poorer in the high serum HFABP with AKI group than in the other groups. Conclusions The s-H-FABP level is an effective biomarker for detecting AKI in non-surgical intensive care patients.
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Affiliation(s)
- Akihiro Shirakabe
- Division of Intensive Care Unit, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan.
| | - Nobuaki Kobayashi
- Division of Intensive Care Unit, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan
| | - Noritake Hata
- Division of Intensive Care Unit, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan
| | - Takuro Shinada
- Division of Intensive Care Unit, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan
| | - Kazunori Tomita
- Division of Intensive Care Unit, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan
| | - Masafumi Tsurumi
- Division of Intensive Care Unit, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan
| | - Hirotake Okazaki
- Division of Intensive Care Unit, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan
| | - Masato Matsushita
- Division of Intensive Care Unit, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan
| | - Yoshiya Yamamoto
- Division of Intensive Care Unit, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan
| | - Shinya Yokoyama
- Division of Intensive Care Unit, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan
| | - Kuniya Asai
- Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
| | - Wataru Shimizu
- Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
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Güneş A, Ece A, Akça H, Aktar F, Mete Ş, Samanci S, Uluca Ü, Şen V, Tan İ, Kaplan İ. Urinary kidney injury molecules in children with febrile seizures. Ren Fail 2016; 38:1377-1382. [DOI: 10.1080/0886022x.2016.1215198] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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Affiliation(s)
- Eun-Ho Lee
- Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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