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Yousef Almulhim M. The efficacy of novel biomarkers for the early detection and management of acute kidney injury: A systematic review. PLoS One 2025; 20:e0311755. [PMID: 39879206 DOI: 10.1371/journal.pone.0311755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Accepted: 09/24/2024] [Indexed: 01/31/2025] Open
Abstract
Acute kidney injury (AKI) is a frequent clinical complication lacking early diagnostic tests and effective treatments. Novel biomarkers have shown promise for enabling earlier detection, risk stratification, and guiding management of AKI. We conducted a systematic review to synthesize evidence on the efficacy of novel biomarkers for AKI detection and management. Database searches yielded 17 relevant studies which were critically appraised. Key themes were biomarker efficacy in predicting AKI risk and severity before functional changes; potential to improve clinical management through earlier diagnosis, prognostic enrichment, and guiding interventions; emerging roles as therapeutic targets and prognostic tools; and ongoing challenges requiring further validation. Overall, novel biomarkers like neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cell cycle arrest markers ([TIMP-2] •[IGFBP7]) demonstrate capability for very early AKI prediction and accurate risk stratification. Their incorporation has potential to facilitate timely targeted interventions and personalized management. However, factors influencing biomarker performance, optimal cutoffs, cost-effectiveness, and impact on patient outcomes require robust validation across diverse settings before widespread implementation. Addressing these limitations through ongoing research can help translate novel biomarkers into improved detection, prognosis, and management of AKI in clinical practice.
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Zywno H, Figiel W, Grat M, Nazarewski S, Galazka Z, Malyszko J. Can Novel Biomarkers Effectively Predict Acute Kidney Injury in Liver or Kidney Transplant Recipients? Int J Mol Sci 2024; 25:12072. [PMID: 39596140 PMCID: PMC11593440 DOI: 10.3390/ijms252212072] [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: 10/22/2024] [Revised: 11/05/2024] [Accepted: 11/09/2024] [Indexed: 11/28/2024] Open
Abstract
Acute kidney injury (AKI) constitutes a common complication associated with liver or kidney transplantation, which may significantly impact the graft condition and perioperative mortality. Current AKI diagnostic criteria based on serum creatinine (sCr) and urine output alterations are widely utilized in routine clinical practice. However, the diagnostic value of sCr may be limited by various confounding factors, including age, sex, reduced or increased muscle mass, and pre-existing chronic kidney disease (CKD). Furthermore, sCr is rather a late indicator of AKI, as its concentration tends to increase only when the severity of the injury is enough to decrease the estimated glomerular filtration rate (eGFR). Recent expertise highlights the need for novel biomarkers in post-transplantation AKI diagnosis, prediction of event-associated mortality, or evaluation of indications for renal replacement treatment (RRT). Over the last decade, the diagnostic performance of various AKI biomarkers has been assessed, among which some showed the potential to outperform sCr in AKI diagnosis. Identifying susceptible individuals, early diagnosis, and prompt intervention are crucial for successful transplantation, undisturbed graft function in long-term follow-up, and decreased mortality. However, the research on AKI biomarkers in transplantation still needs to be explored. The field lacks consistent results, rigorous study designs, and external validation. Considering the rapidly growing prevalence of CKD and cirrhosis that are associated with the transplantation at their end-stage, as well as the existing knowledge gap, the aim of this article was to provide the most up-to-date review of the studies on novel biomarkers in the diagnosis of post-transplantation AKI.
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Affiliation(s)
- Hubert Zywno
- Department of Nephrology, Dialysis, and Internal Diseases, University Clinical Centre, Medical University of Warsaw, 02-097 Warsaw, Poland;
- Doctoral School of Medical University of Warsaw, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Wojciech Figiel
- Department of General, Transplant, and Liver Surgery, University Clinical Centre, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Michal Grat
- Department of General, Transplant, and Liver Surgery, University Clinical Centre, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Slawomir Nazarewski
- Department of General, Endocrinological, and Vascular Surgery, University Clinical Centre, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Zbigniew Galazka
- Department of General, Endocrinological, and Vascular Surgery, University Clinical Centre, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Jolanta Malyszko
- Department of Nephrology, Dialysis, and Internal Diseases, University Clinical Centre, Medical University of Warsaw, 02-097 Warsaw, Poland;
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Platt E, Robertson F, Al-Rashed A, Klootwijk R, Hall A, Quaglia A, Salama A, Heptinstall L, Davidson B. NGAL in the Development of Acute Kidney Injury in a Murine Model of Remote Ischaemic Preconditioning and Liver Ischaemia Reperfusion. Int J Mol Sci 2024; 25:5061. [PMID: 38791106 PMCID: PMC11121231 DOI: 10.3390/ijms25105061] [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: 02/22/2024] [Revised: 03/22/2024] [Accepted: 03/25/2024] [Indexed: 05/26/2024] Open
Abstract
Acute kidney injury (AKI) is common following liver transplantation and is associated with liver ischeamia reperfusion (IR) injury. The purpose of this study was to use a mouse model of liver IR injury and AKI to study the role of Neutrophil Gelatinase Associated Lipocalin (NGAL), a biomarker of AKI, in liver IR injury and AKI. We demonstrate an adapted, reproducible model of liver IR injury and AKI in which remote ischemic preconditioning (RIPC) by repeated episodes of hindleg ischemia prior to liver IR reduced the severity of the IR injury. In this model, serum NGAL at 2 h post reperfusion correlated with AKI development early following IR injury. This early rise in serum NGAL was associated with hepatic but not renal upregulation of NGAL mRNA, suggesting NGAL production in the liver but not the kidney in the early phase post liver IR injury.
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Affiliation(s)
- Esther Platt
- Division of Surgery and Interventional Science, University College London, London NW3 2PF, UK; (E.P.); (F.R.)
| | - Francis Robertson
- Division of Surgery and Interventional Science, University College London, London NW3 2PF, UK; (E.P.); (F.R.)
| | - Ali Al-Rashed
- Department of Renal Medicine, University College London, London NW3 2PF, UK; (A.A.-R.); (A.S.)
| | - Riko Klootwijk
- Department of Renal Medicine, University College London, London NW3 2PF, UK; (A.A.-R.); (A.S.)
| | - Andrew Hall
- Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London NW3 2QG, UK
| | - Alberto Quaglia
- Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London NW3 2QG, UK
| | - Alan Salama
- Department of Renal Medicine, University College London, London NW3 2PF, UK; (A.A.-R.); (A.S.)
| | - Lauren Heptinstall
- Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London NW3 2QG, UK
| | - Brian Davidson
- Division of Surgery and Interventional Science, University College London, London NW3 2PF, UK; (E.P.); (F.R.)
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Raja K, Panackel C. Post Liver Transplant Renal Dysfunction-Evaluation, Management and Immunosuppressive Practice. J Clin Exp Hepatol 2024; 14:101306. [PMID: 38274509 PMCID: PMC10806298 DOI: 10.1016/j.jceh.2023.101306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 11/21/2023] [Indexed: 01/27/2024] Open
Abstract
Liver transplantation (LT) is an effective and lifesaving treatment for patients with end-stage liver disease and hepatocellular carcinoma. Significant improvement in intermediate and long-term survival has been possible due to advancements in immunosuppressive therapy, perioperative care, and surgical techniques. Despite these advances, metabolic complications, including diabetes mellitus, cardiovascular diseases, malignancies, and renal dysfunction, are challenging issues after LT. Acute kidney injury (AKI) and chronic kidney disease (CKD) after LT are common and result in significant morbidity and mortality. Early diagnosis of kidney injury after LT is challenging, and no technique has yet proven effective in prediction of renal dysfunction. The methods for assessing renal function range from formulas that predict glomerular filtration rate to non-invasive biomarkers. The universal adoption of the model for end-stage liver disease has a direct impact on the incidence of peri-transplant AKI and development of CKD in the long-term. Post-LT renal dysfunction is multifactorial and is usually a result of pre-transplantation comorbidities, occurrence of renal dysfunction on the waiting list, perioperative events, and post-transplant nephrotoxic immunosuppressive medication use. Early identification of patients at risk for renal dysfunction and adoption of preventive measures are crucial in the pre-transplant period. No data are currently available to suggest a surgical technique that reliably demonstrates renal protection. Nephroprotective strategies during LT follow accepted surgical practice guidelines, such as maintenance of intravascular volume and mean arterial pressure. The management of kidney disease following LT is challenging, as by the time the serum creatinine is significantly elevated, few interventions impact the course of progression. Early nephroprotective measures are strongly advised and they mostly center on delaying the administration of calcineurin inhibitors (CNIs) during the initial postoperative period, lowering CNI dosage and combining CNI with mycophenolate mofetil and everolimus. The reasons for renal failure following LT, the techniques used to diagnose it, and the therapies designed to preserve renal function both immediately and late after LT are all critically evaluated in this review.
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Affiliation(s)
- Kaiser Raja
- Department of Gastroenterology and Hepatology, King's College Hospital London, Dubai, United Arab Emirates
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He S, He L, Yan F, Li J, Liao X, Ling M, Jing R, Pan L. Identification of hub genes associated with acute kidney injury induced by renal ischemia-reperfusion injury in mice. Front Physiol 2022; 13:951855. [PMID: 36246123 PMCID: PMC9557154 DOI: 10.3389/fphys.2022.951855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 09/07/2022] [Indexed: 12/03/2022] Open
Abstract
Background: Acute kidney injury (AKI) is a severe clinical syndrome, and ischemia-reperfusion injury is an important cause of acute kidney injury. The aim of the present study was to investigate the related genes and pathways in the mouse model of acute kidney injury induced by ischemia-reperfusion injury (IRI-AKI). Method: Two public datasets (GSE39548 and GSE131288) originating from the NCBI Gene Expression Omnibus (GEO) database were analyzed using the R software limma package, and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) and gene set enrichment analysis (GSEA) were performed using the differentially expressed genes. Furthermore, a protein-protein interaction (PPI) network was constructed to investigate hub genes, and transcription factor (TF)-hub gene and miRNA-hub gene networks were constructed. Drugs and molecular compounds that could interact with hub genes were predicted using the DGIdb. Result: A total of 323 common differentially expressed genes were identified in the renal ischemia-reperfusion injury group compared with the control group. Among these, 260 differentially expressed genes were upregulated and 66 differentially expressed genes were downregulated. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis results showed that these common differentially expressed genes were enriched in positive regulation of cytokine production, muscle tissue development, and other biological processes, indicating that they were involved in mitogen-activated protein kinase (MAPK), PI3K-Akt, TNF, apoptosis, and Epstein-Barr virus infection signaling pathways. Protein-protein interaction analysis showed 10 hub genes, namely, Jun, Stat3, MYC, Cdkn1a, Hif1a, FOS, Atf3, Mdm2, Egr1, and Ddit3. Using the STRUST database, starBase database, and DGIdb database, it was predicted that 34 transcription factors, 161 mi-RNAs, and 299 drugs or molecular compounds might interact with hub genes. Conclusion: Our findings may provide novel potential biomarkers and insights into the pathogenesis of ischemia-reperfusion injury-acute kidney injury through a comprehensive analysis of Gene Expression Omnibus data, which may provide a reliable basis for early diagnosis and treatment of ischemia-reperfusion injury-acute kidney injury.
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Affiliation(s)
- Sheng He
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
- Guangxi Engineering Research Center for Tissue and Organ Injury and Repair Medicine, Nanning, China
- Guangxi Key Laboratory for Basic Science and Prevention of Perioperative Organ Disfunction, Nanning, China
- Guangxi Clinical Research Center for Anesthesiology, Nanning, China
- Department of Anesthesiology, The First Affiliated Hospital of Southern China University, Hengyang, China
| | - Lili He
- Department of Anesthesiology, The Second Affiliated Hospital of Southern China University, Hengyang, China
| | - Fangran Yan
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Junda Li
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Xiaoting Liao
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Maoyao Ling
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Ren Jing
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Linghui Pan
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
- Guangxi Engineering Research Center for Tissue and Organ Injury and Repair Medicine, Nanning, China
- Guangxi Key Laboratory for Basic Science and Prevention of Perioperative Organ Disfunction, Nanning, China
- Guangxi Clinical Research Center for Anesthesiology, Nanning, China
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Asrani SK, Shankar N, da Graca B, Nadim MK, Cardenas A. Role of Novel Kidney Biomarkers in Patients With Cirrhosis and After Liver Transplantation. Liver Transpl 2022; 28:466-482. [PMID: 34714972 DOI: 10.1002/lt.26344] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 10/19/2021] [Accepted: 10/21/2021] [Indexed: 01/13/2023]
Abstract
Acute kidney injury (AKI) and chronic kidney disease (CKD) are important drivers of morbidity and mortality in patients with cirrhosis before and after liver transplantation (LT). In this review, we examine the role of novel kidney biomarkers for early recognition of kidney injury. Studies are limited by lack of reference standards, heterogeneous definitions of outcomes and biomarker cutoffs, and inconsistent diagnostic performance. Overall, a change in biomarker is more relevant than an absolute cutoff. Cystatin C and urinary neutrophil gelatinase-associated lipocalin (uNGAL) are the most studied candidate biomarkers and identify AKI or progression of AKI earlier than serum creatinine (sCr). Kidney injury molecule 1 and liver-type fatty acid-binding protein (L-FABP) also show potential. NGAL and interleukin 18 may play a role in differentiating acute tubular necrosis from other forms of AKI. Combining novel biomarkers with the Model for End-Stage Liver Disease score may assist prognosis. Persistent elevations in select markers (eg, NGAL) can portend irreversible injury. Several pretransplantation markers (including sCr) predict posttransplantation kidney dysfunction. Pretransplantation assessment of clinical factors (eg, age, diabetes) and novel markers (osteopontin and tissue inhibitor of metalloproteinases 1 [TIMP-1]) may predict renal kidney recovery after LT. Intraoperative changes in biomarkers predict early post-LT AKI. Prediction of CKD remains difficult, although a combination of biomarkers (eg, beta-2 microglobulin, CD40) is promising. Novel biomarkers have yet to replace sCr in guideline-based evaluation and management of kidney dysfunction in patients with cirrhosis. We propose a theoretical framework for practical incorporation of these biomarkers that considers patient characteristics (risk for irreversible injury), markers of functional and structural change, and assessment of the AKI-CKD continuum to identify patients at the highest risk for progressive kidney disease before and after LT.
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Affiliation(s)
| | | | | | - Mitra K Nadim
- Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Andres Cardenas
- GI/Liver Transplant Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clinic, Barcelona, Spain.,Faculty of Medicine, University of Barcelona, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
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7
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Pacheco MP, Carneiro-D'Albuquerque LA, Mazo DF. Current aspects of renal dysfunction after liver transplantation. World J Hepatol 2022; 14:45-61. [PMID: 35126839 PMCID: PMC8790396 DOI: 10.4254/wjh.v14.i1.45] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 10/24/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
The development of chronic kidney disease (CKD) after liver transplantation (LT) exerts a severe effect on the survival of patients. The widespread adoption of the model for end-stage liver disease score strongly impacted CKD incidence after the procedure, as several patients are transplanted with previously deteriorated renal function. Due to its multifactorial nature, encompassing pre-transplantation conditions, perioperative events, and nephrotoxic immunosuppressor therapies, the accurate identification of patients under risk of renal disease, and the implementation of preventive approaches, are extremely important. Methods for the evaluation of renal function in this setting range from formulas that estimate the glomerular filtration rate, to non-invasive markers, although no option has yet proved efficient in early detection of kidney injury. Considering the nephrotoxicity of calcineurin inhibitors (CNI) as a factor of utmost importance after LT, early nephroprotective strategies are highly recommended. They are based mainly on delaying the application of CNI during the immediate postoperative-period, reducing their dosage, and associating them with other less nephrotoxic drugs, such as mycophenolate mofetil and everolimus. This review provides a critical assessment of the causes of renal dysfunction after LT, the methods of its evaluation, and the interventions aimed at preserving renal function early and belatedly after LT.
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Affiliation(s)
- Mariana P Pacheco
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, Sao Paulo 05403-900, Sao Paulo, Brazil
| | - Luiz Augusto Carneiro-D'Albuquerque
- Division of Digestive Organs Transplant, Department of Gastroenterology, University of São Paulo School of Medicine, Sao Paulo 05403-900, Sao Paulo, Brazil
| | - Daniel F Mazo
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, Sao Paulo 05403-900, Sao Paulo, Brazil
- Division of Gastroenterology, Department of Internal Medicine, School of Medical Sciences of University of Campinas, Campinas 13083-878, Sao Paulo, Brazil
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Platt E, Klootwijk E, Salama A, Davidson B, Robertson F. Literature review of the mechanisms of acute kidney injury secondary to acute liver injury. World J Nephrol 2022; 11:13-29. [PMID: 35117976 PMCID: PMC8790308 DOI: 10.5527/wjn.v11.i1.13] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/12/2021] [Accepted: 12/25/2021] [Indexed: 02/06/2023] Open
Abstract
People exposed to liver ischaemia reperfusion (IR) injury often develop acute kidney injury and the combination is associated with significant morbidity and mortality. Molecular mediators released by the liver in response to IR injury are the likely cause of acute kidney injury (AKI) in this setting, but the mediators have not yet been identified. Identifying the mechanism of injury will allow the identification of therapeutic targets which may modulate both liver IR injury and AKI following liver IR injury.
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Affiliation(s)
- Esther Platt
- Division of Surgery and Interventional Science, University College London, London NW3 2QG, United Kingdom
| | - Enriko Klootwijk
- Department of Renal Medicine, University College London, London NW3 2PF, United Kingdom
| | - Alan Salama
- Department of Renal Medicine, University College London, London NW3 2PF, United Kingdom
| | - Brian Davidson
- Division of Surgery and Interventional Science, University College London, London NW3 2QG, United Kingdom
| | - Francis Robertson
- Division of Surgery and Interventional Science, University College London, London NW3 2QG, United Kingdom
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9
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Intraoperative systemic biomarkers predict post-liver transplantation acute kidney injury. Eur J Gastroenterol Hepatol 2021; 33:1556-1563. [PMID: 33079777 DOI: 10.1097/meg.0000000000001892] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Liver transplant (LT) is a definitive therapeutic option for patients with chronic liver disease. However, acute kidney injury after LT (post-LT AKI) is a frequent complication that may lead to graft dysfunction and decrease life expectancy. Delay in AKI detection by traditional biomarkers boosted research with new biomarkers for post-LT AKI as neutrophil gelatinase-associated lipocalin (NGAL) and syndecan-1. We aim to evaluate associations of intraoperative systemic NGAL and syndecan-1 levels with post-LT AKI. METHODS This is a prospective study conducted in 46 patients selected for LT. Patients were evaluated preoperatively and blood samples were collected intraoperatively: T1 (after induction of anesthesia), T2 (anhepatic phase) and T3 (2 h after reperfusion of the graft). RESULTS The mean age was 54 ± 12 years and 60% were male. Post-LT AKI was observed in 24 (52%) patients of which 12% needed dialysis. Serum NGAL and syndecan-1 increased along surgical phases. Mostly, increment values of serum NGAL of T2 to T3 and syndecan-1 at T3 were importantly associated with post-LT AKI. Into a multivariate model with model for end-stage liver disease score, age, gender, warm ischemia, cold ischemia and surgery time, syndecan-1 levels at T3 remains capable to predict post-LT AKI. Serum NGAL had significance only with increment values calculated by the ratio of 'T3/T2'. Finally, serum syndecan-1 at T3 had a better diagnostic performance in receiver operating characteristic curve analysis. CONCLUSION Serum syndecan-1 levels in 2 h after reperfusion were most useful in early post-LT AKI diagnosis and may be used to construct new risk groups in this context.
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Lima C, de Paiva Haddad LB, de Melo PDV, Malbouisson LM, do Carmo LPF, D'Albuquerque LAC, Macedo E. Early detection of acute kidney injury in the perioperative period of liver transplant with neutrophil gelatinase-associated lipocalin. BMC Nephrol 2019; 20:367. [PMID: 31615452 PMCID: PMC6794911 DOI: 10.1186/s12882-019-1566-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 09/26/2019] [Indexed: 12/28/2022] Open
Abstract
Background Acute kidney injury (AKI) is a common complication in patients undergoing liver transplant (LT) and is associated with high morbidity and mortality. We aim to evaluate the pattern of urine and plasma neutrophil gelatinase-associated lipocalin (NGAL) elevation during the perioperative period of LT and to assess it as a prognostic marker for AKI progression, need for dialysis and mortality. Methods We assessed NGAL levels before induction of anesthesia, after portal reperfusion and at 6, 18, 24, and 48 h after surgery. Patients were monitored daily during the first week after LT. Results Of 100 enrolled patients undergoing liver transplant, 59 developed severe AKI based on the KDIGO serum creatinine (sCr) criterion; 34 were dialysed, and 21 died within 60 days after LT. Applying a cut-off value of 136 ng/ml, UNGAL values 6 h after surgery was a good predictor of AKI development within 7 days after surgery, having a positive predictive value (PPV) of 80% with an AUC of 0.76 (95% CI 0.67–0.86). PNGAL at 18 h after LT was also a good predictor of AKI in the first week, having a PPV of 81% and AUC of 0.74 (95% CI 0.60–0.88). Based on PNGAL and UNGAL cut-off criteria levels, time to AKI diagnosis was 28 and 23 h earlier than by sCr, respectively. The best times to assess the need for dialysis were 18 h after LT by PNGAL and 06 h after LT by UNGAL. Conclusion In conclusion, the plasma and urine NGAL elevation pattern in the perioperative period of the liver transplant can predict AKI diagnosis earlier. UNGAL was an early independent predictor of AKI development and need for dialysis. Further studies are needed to assess whether the clinical use of biomarkers can improve patient outcomes. Trial registration Registered at Clinical Trials (clinicaltrials.gov) in March 24th, 2014 by title “Acute Kidney Injury Biomarkers: Diagnosis and Application in Pre-operative Period of Liver Transplantation (AKIB)” and identifier NCT02095431, retrospectively registered.
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Affiliation(s)
- Camila Lima
- Department of Internal Medicine, Nephrology Division, University of Sao Paulo, Present Address: 419 Av. Dr Enéas de Carvalho Aguiar, third floor - room 340, 05403-000, Cerqueira Cesar, São Paulo, Brazil. .,Department of Medical Surgical Nursing, University of Sao Paulo Nursing School, Sao Paulo, Brazil.
| | - Luciana Bertocco de Paiva Haddad
- Department of Gastrointestinal Surgery, Clinical Surgery Division, University of Sao Paulo, Sao Paulo, Brazil.,Present Address: La Jolla, San Diego, USA
| | | | - Luiz Marcelo Malbouisson
- Department of Anaesthesiology, Clinical Surgery Division, University of Sao Paulo, Sao Paulo, Brazil
| | - Lilian Pires Freitas do Carmo
- Department of Internal Medicine, Nephrology Division, University of Sao Paulo, Present Address: 419 Av. Dr Enéas de Carvalho Aguiar, third floor - room 340, 05403-000, Cerqueira Cesar, São Paulo, Brazil
| | | | - Etienne Macedo
- Department of Internal Medicine, Nephrology Division, University of Sao Paulo, Present Address: 419 Av. Dr Enéas de Carvalho Aguiar, third floor - room 340, 05403-000, Cerqueira Cesar, São Paulo, Brazil.,Department of Medicine, Nephrology Division, University of California San Diego, San Diego, USA
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