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Lee PH, Huang SM, Tsai YC, Wang YT, Chew FY. Biomarkers in Contrast-Induced Nephropathy: Advances in Early Detection, Risk Assessment, and Prevention Strategies. Int J Mol Sci 2025; 26:2869. [PMID: 40243457 PMCID: PMC11989060 DOI: 10.3390/ijms26072869] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 03/17/2025] [Accepted: 03/18/2025] [Indexed: 04/18/2025] Open
Abstract
Contrast-induced nephropathy (CIN) represents a significant complication associated with the use of iodinated contrast media (ICM), especially in individuals with preexisting renal impairment. The pathophysiology of CIN encompasses oxidative stress, inflammation, endothelial dysfunction, and hemodynamic disturbances, resulting in acute kidney injury (AKI). Early detection is essential for effective management; however, conventional markers like serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) exhibit limitations in sensitivity and timeliness. This review emphasizes the increasing significance of novel biomarkers in enhancing early detection and risk stratification of contrast-induced nephropathy (CIN). Recent advancements in artificial intelligence and computational analytics have improved the predictive capabilities of these biomarkers, enabling personalized risk assessment and precision medicine strategies. Additionally, we discuss mitigation strategies, including hydration protocols, pharmacological interventions, and procedural modifications, aimed at reducing CIN incidence. Incorporating biomarker-driven assessments into clinical decision-making can enhance patient management and outcomes. Future research must prioritize the standardization of biomarker assays, the validation of predictive models across diverse patient populations, and the exploration of novel therapeutic targets. Utilizing advancements in biomarkers and risk mitigation strategies allows clinicians to improve the safety of contrast-enhanced imaging and reduce the likelihood of renal injury.
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Affiliation(s)
- Pei-Hua Lee
- Department of Medical Imaging, China Medical University Hospital, Taichung 404, Taiwan
- Department of Radiology, School of Medicine, China Medical University, Taichung 404, Taiwan
| | - Shao Min Huang
- Department of Medical Education, Show Chwan Memorial Hospital, Changhua 500, Taiwan
| | - Yi-Ching Tsai
- Division of Endocrinology, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan
| | - Yu-Ting Wang
- Department of Pathology, Chung Shan Medical University Hospital, Taichung 402, Taiwan
- Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Fatt Yang Chew
- Department of Medical Imaging, China Medical University Hospital, Taichung 404, Taiwan
- Department of Radiology, School of Medicine, China Medical University, Taichung 404, Taiwan
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2
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Liu Y, Li C, Yang X, Guo S, Cui Z, Kang H, Ma Z, Wang H. Neutrophil Gelatinase-Associated Lipocalin and Interleukin-18 in the Prediction of Acute Kidney Injury in Sepsis Patients. Int J Gen Med 2024; 17:6335-6341. [PMID: 39712197 PMCID: PMC11663376 DOI: 10.2147/ijgm.s489826] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 11/09/2024] [Indexed: 12/24/2024] Open
Abstract
Objective We assessed the predictive value of blood neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) in predicting the onset of acute kidney injury (AKI) in sepsis patients in the intensive care unit (ICU). Methods In this retrospective analysis, we examined the medical records of sepsis patients admitted to the ICU. After ICU admission, blood samples were taken at 0 h, 6 h, 12 h, 24 h, and 48 h. Using an enzyme-linked immunosorbent assay, the concentrations of serum creatinine, NGAL, and IL-18 were determined. Results This study comprised a total of 197 participants, 104 of whom had AKI and 93 of whom did not. Blood concentrations of NGAL and IL-18 increased prior to serum creatinine levels. Between 6-48 hours after ICU administration, NGAL and IL-18 levels in the AKI group were considerably higher than those in the non-AKI group, and creatinine levels between the two groups were significantly different after 48 hours. Based on receiver operating characteristic (ROC) curve analysis, the area under the curve of NGAL and IL-18 for predicting AKI was 0.781 and 0.883, respectively. Conclusion Blood NGAL and IL-18 are potential biomarkers for the early prediction of AKI in sepsis patients in the ICU.
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Affiliation(s)
- Yajing Liu
- Intensive Care Unit, Hengshui People’s Hospital (Harrison International Peace Hospital), Hengshui, 053000, People’s Republic of China
| | - Chunming Li
- Department of Pain, Hengshui Second People’s Hospital, Hengshui, 053000, People’s Republic of China
| | - Xiaoya Yang
- Intensive Care Unit, Hengshui People’s Hospital (Harrison International Peace Hospital), Hengshui, 053000, People’s Republic of China
| | - Shufen Guo
- Intensive Care Unit, Hengshui People’s Hospital (Harrison International Peace Hospital), Hengshui, 053000, People’s Republic of China
| | - Zhaobo Cui
- Intensive Care Unit, Hengshui People’s Hospital (Harrison International Peace Hospital), Hengshui, 053000, People’s Republic of China
| | - Hongshan Kang
- Intensive Care Unit, Hengshui People’s Hospital (Harrison International Peace Hospital), Hengshui, 053000, People’s Republic of China
| | - Zhen Ma
- Intensive Care Unit, Hengshui People’s Hospital (Harrison International Peace Hospital), Hengshui, 053000, People’s Republic of China
| | - Huiqing Wang
- Intensive Care Unit, Hengshui People’s Hospital (Harrison International Peace Hospital), Hengshui, 053000, People’s Republic of China
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3
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González-Nicolás MÁ, González-Guerrero C, Goicoechea M, Boscá L, Valiño-Rivas L, Lázaro A. Biomarkers in Contrast-Induced Acute Kidney Injury: Towards A New Perspective. Int J Mol Sci 2024; 25:3438. [PMID: 38542410 PMCID: PMC10970772 DOI: 10.3390/ijms25063438] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 03/08/2024] [Accepted: 03/17/2024] [Indexed: 01/09/2025] Open
Abstract
Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, especially in patients with underlying pre-existing renal function impairment, cardiovascular disease, or diabetes that could rapidly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network), and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on traditional "gold standard" biomarkers known as serum creatinine, glomerular filtration rate, and urinary output, new reliable serum and urinary biomarkers are still needed for an effective unified diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration, and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.
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Affiliation(s)
- María Ángeles González-Nicolás
- Renal Physiopathology Laboratory, Department of Nephrology, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28009 Madrid, Spain; (M.Á.G.-N.); (C.G.-G.)
| | - Cristian González-Guerrero
- Renal Physiopathology Laboratory, Department of Nephrology, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28009 Madrid, Spain; (M.Á.G.-N.); (C.G.-G.)
| | - Marian Goicoechea
- Department of Nephrology, Hospital General Universitario Gregorio Marañón, 28009 Madrid, Spain;
| | - Lisardo Boscá
- Instituto de Investigaciones Biomédicas Alberto Sols-Morreale (CSIC-UAM), 28029 Madrid, Spain;
- Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Melchor Fernández Almagro 6, 28029 Madrid, Spain
| | - Lara Valiño-Rivas
- Renal Physiopathology Laboratory, Department of Nephrology, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28009 Madrid, Spain; (M.Á.G.-N.); (C.G.-G.)
| | - Alberto Lázaro
- Renal Physiopathology Laboratory, Department of Nephrology, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28009 Madrid, Spain; (M.Á.G.-N.); (C.G.-G.)
- Department of Physiology, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
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Nourie N, Ghaleb R, Lefaucheur C, Louis K. Toward Precision Medicine: Exploring the Landscape of Biomarkers in Acute Kidney Injury. Biomolecules 2024; 14:82. [PMID: 38254682 PMCID: PMC10813773 DOI: 10.3390/biom14010082] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 01/02/2024] [Accepted: 01/06/2024] [Indexed: 01/24/2024] Open
Abstract
Acute kidney injury (AKI) remains a complex challenge with diverse underlying pathological mechanisms and etiologies. Current detection methods predominantly rely on serum creatinine, which exhibits substantial limitations in specificity and poses the issue of late-stage detection of kidney injury. In this review, we propose an up-to-date and comprehensive summary of advancements that identified novel biomarker candidates in blood and urine and ideal criteria for AKI biomarkers such as renal injury specificity, mechanistic insight, prognostic capacity, and affordability. Recently identified biomarkers not only indicate injury location but also offer valuable insights into a range of pathological processes, encompassing reduced glomerular filtration rate, tubular function, inflammation, and adaptive response to injury. The clinical applications of AKI biomarkers are becoming extensive and serving as relevant tools in distinguishing acute tubular necrosis from other acute renal conditions. Also, these biomarkers can offer significant insights into the risk of progression to chronic kidney disease CKD and in the context of kidney transplantation. Integration of these biomarkers into clinical practice has the potential to improve early diagnosis of AKI and revolutionize the design of clinical trials, offering valuable endpoints for therapeutic interventions and enhancing patient care and outcomes.
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Affiliation(s)
- Nicole Nourie
- Department of Nephrology and Kidney Transplantation, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, 75010 Paris, France
- Human Immunology and Immunopathology, Inserm UMR 976, Université Paris Cité, 75010 Paris, France
| | - Rita Ghaleb
- Faculty of Medicine, Saint Joseph University, Beirut 1104 2020, Lebanon
| | - Carmen Lefaucheur
- Department of Nephrology and Kidney Transplantation, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, 75010 Paris, France
- Human Immunology and Immunopathology, Inserm UMR 976, Université Paris Cité, 75010 Paris, France
| | - Kevin Louis
- Department of Nephrology and Kidney Transplantation, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, 75010 Paris, France
- Human Immunology and Immunopathology, Inserm UMR 976, Université Paris Cité, 75010 Paris, France
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5
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Rossiter A, La A, Koyner JL, Forni LG. New biomarkers in acute kidney injury. Crit Rev Clin Lab Sci 2024; 61:23-44. [PMID: 37668397 DOI: 10.1080/10408363.2023.2242481] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 05/14/2023] [Accepted: 07/26/2023] [Indexed: 09/06/2023]
Abstract
Acute kidney injury (AKI) is a commonly encountered clinical syndrome. Although it often complicates community acquired illness, it is more common in hospitalized patients, particularly those who are critically ill or who have undergone major surgery. Approximately 20% of hospitalized adult patients develop an AKI during their hospital care, and this rises to nearly 60% in the critically ill, depending on the population being considered. In general, AKI is more common in older adults, in those with preexisting chronic kidney disease and in those with known risk factors for AKI (including diabetes and hypertension). The development of AKI is associated with an increase in both mortality and morbidity, including the development of post-AKI chronic kidney disease. Currently, AKI is defined by a rise in serum creatinine from either a known or derived baseline value and/or oliguria or anuria. However, clinicians may fail to recognize the initial development of AKI because of a delay in the rise of serum creatinine or because of inaccurate urine output monitoring. This, in turn, delays any putative measures to treat AKI or to limit its degree. Consequently, efforts have focused on new biomarkers associated with AKI that may allow early recognition of this syndrome with the intent that this will translate into improved patient outcomes. Here we outline current biomarkers associated with AKI and explore their potential in aiding diagnosis, understanding the pathophysiology and directing therapy.
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Affiliation(s)
- Adam Rossiter
- Critical Care Unit, Royal Surrey Hospital, Guildford, Surry, UK
| | - Ashley La
- Department of Medicine, University of Chicago, Chicago, Illinois, USA
| | - Jay L Koyner
- Department of Medicine, University of Chicago, Chicago, Illinois, USA
| | - Lui G Forni
- Critical Care Unit, Royal Surrey Hospital, Guildford, Surry, UK
- School of Medicine, Department of Clinical & Experimental Medicine, Faculty of Health Sciences, University of Surrey, Surry, UK
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Gudsoorkar PS, Nysather J, Thakar CV. Definition, Staging, and Role of Biomarkers in Acute Kidney Injury in the Context of Cardiovascular Interventions. Interv Cardiol Clin 2023; 12:469-487. [PMID: 37673492 DOI: 10.1016/j.iccl.2023.06.004] [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] [Indexed: 09/08/2023]
Abstract
Acute kidney injury (AKI) is a frequently occurring complication of cardiovascular interventions, and associated with adverse outcomes. Therefore, a clear definition of AKI is of paramount importance to enable timely recognition and treatment. Historically, changes in the serum creatinine and urine output have been used to define AKI, and the criteria have evolved over time with better understanding of the impact of AKI on the outcomes. However, the reliance on serum creatinine for these AKI definitions carries numerous limitations including delayed rise, inability to differentiate between hemodynamics versus structural injury and assay variability to name a few.
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Affiliation(s)
- Prakash S Gudsoorkar
- Division of Nephrology and Kidney CARE Program, Department of Medicine, University of Cincinnati, OH, USA; Division of Nephrology and Kidney Clinical Advancement, Research & Education (C.A.R.E.) Program, University of Cincinnati, 231 Albert Sabin Way, OH 45267, USA.
| | - Jacob Nysather
- Division of Nephrology and Kidney CARE Program, Department of Medicine, University of Cincinnati, OH, USA; Division of Nephrology and Kidney Clinical Advancement, Research & Education (C.A.R.E.) Program, University of Cincinnati, 231 Albert Sabin Way, OH 45267, USA
| | - Charuhas V Thakar
- Division of Nephrology and Kidney CARE Program, Department of Medicine, University of Cincinnati, OH, USA; Division of Nephrology and Kidney Clinical Advancement, Research & Education (C.A.R.E.) Program, University of Cincinnati, 231 Albert Sabin Way, OH 45267, USA; Department of Nephrology, Veterans Administration Medical Center, Cincinnati, OH, USA
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7
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Feitosa MPM, Lima EG, Abizaid AAC, Mehran R, Lopes NHM, de Assis Fischer Ramos T, Hideo-Kajita A, Filho RK, Junior CVS. The safety of SGLT-2 inhibitors in diabetic patients submitted to elective percutaneous coronary intervention regarding kidney function: SAFE-PCI pilot study. Diabetol Metab Syndr 2023; 15:138. [PMID: 37365618 DOI: 10.1186/s13098-023-01107-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/08/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUND Percutaneous coronary intervention (PCI) is one of the most performed well-succeeded therapeutic procedures worldwide, reducing symptoms and improving quality of life. Neutrophil Gelatinase-associated Lipocalin (NGAL) is a biomarker of acute kidney injury (AKI) produced early after an ischemic renal insult. Osmotic diuresis and the vasoconstriction of the afferent arteriole promoted by Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) generate a concern regarding the possibility of dehydration and consequent AKI. There is no consensus on the maintenance or discontinuation of SGTL2i in patients who will undergo PCI. This study aimed to evaluate the safety of empagliflozin in diabetic patients submitted to elective PCI regarding kidney function. METHODS SAFE-PCI trial is a prospective, open-label, randomized (1:1), single-center pilot study and a follow-up of 30 days. The SGLT2i empagliflozin 25 mg daily was initiated at least 15 days before PCI in the intervention group and maintained until the end of the follow-up period. Serum NGAL was collected 6 h after PCI and creatinine before PCI, 24 h, and 48 h after the procedure. As per protocol, both groups received optimal medical treatment and standard protocol of nephroprotection. RESULTS A total of 42 patients were randomized (22 patients in the iSGLT-2 group and 20 patients in the control group). There was no difference between-group baseline data. The primary outcome (NGAL and creatinine values post PCI) did not differ in both groups: the mean NGAL value was 199 ng/dL in the empagliflozin group and 150 ng/dL in the control group (p = 0.249). Although there was an initial increase in creatinine in the SGLT-2i group compared to the control group between baseline creatinine and pre-PCI and 24 h post-PCI creatinine, no difference was detected in creatinine 48 h post-PCI (p = 0.065). The incidence of CI-AKI, determined by KDIGO criteria, in the iSGLT2-group was 13.6% and 10.0% in the control group without statistical difference. CONCLUSION The present study showed that the use of empagliflozin is safe regarding kidney function during elective PCI in patients with T2D when compared with no use of SGLT2i. Trial registration Our clinical study is registered on ClinicalTrials.gov with the following number: NCT05037695.
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Affiliation(s)
- Mateus Paiva Marques Feitosa
- Instituto Do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
- Av. Dr. Eneas de Carvalho Aguiar 44, Departamento de Aterosclerose, 2nd Floor, Cerqueira César, São Paulo, SP, 05403-000, Brazil.
| | - Eduardo Gomes Lima
- Instituto Do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Alexandre Antônio Cunha Abizaid
- Instituto Do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Roxana Mehran
- Icahn School of Medicine at Mount Sinai, New York, USA
| | - Neuza Helena Moreira Lopes
- Instituto Do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Thiago de Assis Fischer Ramos
- Instituto Do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Alexandre Hideo-Kajita
- Instituto Do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Roberto Kalil Filho
- Instituto Do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Carlos Vicente Serrano Junior
- Instituto Do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
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8
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Cheng AS, Li X. The Potential Biotherapeutic Targets of Contrast-Induced Acute Kidney Injury. Int J Mol Sci 2023; 24:8254. [PMID: 37175958 PMCID: PMC10178966 DOI: 10.3390/ijms24098254] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 04/27/2023] [Accepted: 04/28/2023] [Indexed: 05/15/2023] Open
Abstract
Contrast-induced acute kidney injury (CI-AKI) is manifested by an abrupt decline in kidney function as a consequence of intravascular exposure to contrast media. With the increased applicability of medical imaging and interventional procedures that utilize contrast media for clinical diagnosis, CI-AKI is becoming the leading cause of renal dysfunction. The pathophysiological mechanism associated with CI-AKI involves renal medullary hypoxia, the direct toxicity of contrast agents, oxidative stress, apoptosis, inflammation, and epigenetic regulation. To date, there is no effective therapy for CI-AKI, except for the development of strategies that could reduce the toxicity profiles of contrast media. While most of these strategies have failed, evidence has shown that the proper use of personalized hydration, contrast medium, and high-dose statins may reduce the occurrence of CI-AKI. However, adequate risk predication and attempts to develop preventive strategies can be considered as the key determinants that can help eliminate CI-AKI. Additionally, a deeper understanding of the pathophysiological mechanism of CI-AKI is crucial to uncover molecular targets for the prevention of CI-AKI. This review has taken a step further to solidify the current known molecular mechanisms of CI-AKI and elaborate the biomarkers that are used to detect early-stage CI-AKI. On this foundation, this review will analyze the molecular targets relating to apoptosis, inflammation, oxidative stress, and epigenetics, and, thus, provide a strong rationale for therapeutic intervention in the prevention of CI-AKI.
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Affiliation(s)
- Alice Shasha Cheng
- Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA;
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, 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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Rico-Fontalvo J, Aroca-Martínez G, Daza-Arnedo R, Cabrales J, Rodríguez-Yanez T, Cardona-Blanco M, Montejo-Hernández J, Rodelo Barrios D, Patiño-Patiño J, Osorio Rodríguez E. Novel Biomarkers of Diabetic Kidney Disease. Biomolecules 2023; 13:biom13040633. [PMID: 37189380 DOI: 10.3390/biom13040633] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/23/2023] [Accepted: 03/24/2023] [Indexed: 04/03/2023] Open
Abstract
Diabetic kidney disease (DKD) is a highly prevalent condition worldwide. It represents one of the most common complications arising from diabetes mellitus (DM) and is the leading cause of end-stage kidney disease (ESKD). Its development involves three fundamental components: the hemodynamic, metabolic, and inflammatory axes. Clinically, persistent albuminuria in association with a progressive decline in glomerular filtration rate (GFR) defines this disease. However, as these alterations are not specific to DKD, there is a need to discuss novel biomarkers arising from its pathogenesis which may aid in the diagnosis, follow-up, therapeutic response, and prognosis of the disease.
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Petrova I, Alexandrov A, Vladimirov G, Mateev H, Bogov I, Paskaleva I, Gotcheva N. NGAL as Biomarker of Clinical and Subclinical Damage of Kidney Function after Coronary Angiography. Diagnostics (Basel) 2023; 13:diagnostics13061180. [PMID: 36980488 PMCID: PMC10047760 DOI: 10.3390/diagnostics13061180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 02/20/2023] [Accepted: 03/13/2023] [Indexed: 03/22/2023] Open
Abstract
Contrast-induced acute kidney injury (CI-AKI) is a serious complication after angiographic examinations in cardiology. Diagnosis may be delayed based on standard serum creatinine, and subclinical forms of kidney damage may not be detected at all. In our study, we investigate the clinical use in these directions of a “damage”-type biomarker—neutrophil gelatinase-associated lipocalin (NGAL). Among patients with a high-risk profile undergoing scheduled coronary angiography and/or angioplasty, plasma NGAL was determined at baseline and at 4th and 24th h after contrast administration. In the CI-AKI group, NGAL increased significantly at the 4th hour (Me 109.3 (IQR 92.1–148.7) ng/mL versus 97.6 (IQR 69.4–127.0) ng/mL, p = 0.006) and at the 24th hour (Me 131.0 (IQR 81.1–240.8) ng/mL, p = 0.008). In patients with subclinical CI-AKI, NGAL also increased significantly at the 4th hour (Me 94.0 (IQR 75.5–148.2) ng/mL, p = 0.002) and reached levels close to those in patients with CI-AKI. Unlike the new biomarker, however, serum creatinine did not change significantly in this group. The diagnostic power of NGAL is extremely good—AUC 0.847 (95% CI: 0.677–1.000; p = 0.001) in CI-AKI and AUC 0.731 (95% CI: 0.539–0.924; p = 0.024) in subclinical CI-AKI. NGAL may be a reliable biomarker for the early diagnosis of clinical and subclinical forms of renal injury after contrast angiographic studies.
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Affiliation(s)
- Iliyana Petrova
- Clinic of Cardiology, National Heart Hospital, 65 Konioviza Str., 1309 Sofia, Bulgaria
- Correspondence:
| | - Alexander Alexandrov
- Clinic of Cardiology, National Heart Hospital, 65 Konioviza Str., 1309 Sofia, Bulgaria
| | - Georgi Vladimirov
- Clinic of Cardiology, National Heart Hospital, 65 Konioviza Str., 1309 Sofia, Bulgaria
| | - Hristo Mateev
- Clinic of Cardiology, National Heart Hospital, 65 Konioviza Str., 1309 Sofia, Bulgaria
| | - Ivaylo Bogov
- Central hospitalier Châlons-en-Champagne, 51 Rue du Commandant Derrien, 51000 Châlons-en-Champagne, France
| | - Iva Paskaleva
- Laboratory Department, National Heart Hospital, 65 Konioviza Str., 1309 Sofia, Bulgaria
| | - Nina Gotcheva
- Clinic of Cardiology, National Heart Hospital, 65 Konioviza Str., 1309 Sofia, Bulgaria
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11
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Qin Z, Li H, Jiao P, Jiang L, Geng J, Yang Q, Liao R, Su B. The value of urinary interleukin-18 in predicting acute kidney injury: a systematic review and meta-analysis. Ren Fail 2022; 44:1717-1731. [PMID: 36259446 PMCID: PMC9586591 DOI: 10.1080/0886022x.2022.2133728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Aims The aim of this study was to systematically review relevant studies to evaluate the value of urinary interleukin-18 (uIL-18) in predicting acute kidney injury (AKI). Methods A comprehensive search of PubMed, Medline, Embase, and Cochrane Library was conducted for literature published up to 1 August 2022. Quality Assessment Tool for Diagnostic Accuracy Studies-2 (QUADAS-2) was applied to assess the literature quality. Then, relevant data were extracted from each eligible study and a random-effects regression model was utilized to pool sensitivity, specificity, and construct summary receiver operating characteristic (SROC) and area under curve (AUC). Results Twenty-six studies with 7183 patients were enrolled and relevant information was extracted. The estimated sensitivity and specificity of uIL-18 in the diagnosis of AKI were 0.64 (95% confidence interval (CI): 0.54–0.73) and 0.77 (95%CI: 0.71–0.83), respectively. The pooled diagnostic odds ratio (DOR) was 6.08 (95%CI: 3.63–10.18), and the AUC of uIL-18 in predicting AKI was 0.78 (95%CI: 0.74–0.81). Subgroup analysis showed that uIL-18 in pediatric patients was more effective in predicting AKI than in adults (DOR: 7.33 versus 5.75; AUC: 0.81 versus 0.77). Conclusions Urinary IL-18 could be a relatively good biomarker with moderate predictive value for AKI, especially in pediatric patients. However, further research and clinical settings are still needed to validate our findings.
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Affiliation(s)
- Zheng Qin
- Department of Nephrology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China.,Med-X Center for Materials, Sichuan University, Chengdu, China.,Med + Biomaterial Institute of West China Hospital/West China School of Medicine of Sichuan University, Chengdu, China
| | - Hancong Li
- West China School of Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Pengcheng Jiao
- West China School of Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Luojia Jiang
- Department of Nephrology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China.,Med-X Center for Materials, Sichuan University, Chengdu, China.,Med + Biomaterial Institute of West China Hospital/West China School of Medicine of Sichuan University, Chengdu, China
| | - Jiwen Geng
- Department of Nephrology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China.,Med-X Center for Materials, Sichuan University, Chengdu, China.,Med + Biomaterial Institute of West China Hospital/West China School of Medicine of Sichuan University, Chengdu, China
| | - Qinbo Yang
- Department of Nephrology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China.,Med-X Center for Materials, Sichuan University, Chengdu, China.,Med + Biomaterial Institute of West China Hospital/West China School of Medicine of Sichuan University, Chengdu, China
| | - Ruoxi Liao
- Department of Nephrology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China.,Med-X Center for Materials, Sichuan University, Chengdu, China.,Med + Biomaterial Institute of West China Hospital/West China School of Medicine of Sichuan University, Chengdu, China
| | - Baihai Su
- Department of Nephrology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China.,Med-X Center for Materials, Sichuan University, Chengdu, China.,Med + Biomaterial Institute of West China Hospital/West China School of Medicine of Sichuan University, Chengdu, China
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12
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Rosiglitazone Alleviates Contrast-Induced Acute Kidney Injury in Rats via the PPARγ/NLRP3 Signaling Pathway. DISEASE MARKERS 2022; 2022:4158692. [PMID: 36225198 PMCID: PMC9550500 DOI: 10.1155/2022/4158692] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 09/07/2022] [Indexed: 11/17/2022]
Abstract
Background This study investigated the effect and mechanism of rosiglitazone on a rat model with contrast-induced acute kidney injury (CI-AKI). Materials and Methods The CI-AKI rat model was established from Sprague Dawley rats by furosemide injection (10 ml/kg) to the caudal vein followed by iohexol (11.7 ml/kg). The experimental grouping was randomly allocated into control, model, rosiglitazone, and T0070907 groups. Blood samples were collected from the abdominal aorta. Serum creatinine, urea nitrogen, MDA, and SOD contents were detected by biochemical analysis. TNF-α and IL-10 expression was detected by ELISA. Urine creatinine and urine protein were measured following 24-h urine biochemistry testing. Cell pathology and apoptosis were detected by H&E and TUNEL staining, respectively. PPARγ, NLRP3, eNOS, and caspase-3 mRNA expression were detected by qPCR. Caspase-3 and NLRP3 expression were detected by immunohistochemistry. Results The CI-AKI rat model was successfully established because the results showed that compared with control, serum creatinine, urea nitrogen, MDA, SOD, TNF-α, and IL-10, urine creatinine and urine protein levels were significantly increased in the model group, indicating AKI, but was significantly decreased with rosiglitazone treatment, indicating recovery from injury, while opposite results were obtained with SOD. Apoptosis rate was significantly increased in the model group and significantly decreased with rosiglitazone treatment. NLRP3 and eNOS increased significantly in the model group and decreased significantly with rosiglitazone treatment, while opposite results were obtained with PPARγ. NLRP3 and caspase-3 protein expression was significantly increased in the model group and significantly decreased with rosiglitazone treatment. Conclusion Rosiglitazone could alleviate acute renal injury in the CI-AKI rat model by regulating the PPARγ/NLRP3 signaling pathway and should be further investigated as a potential treatment in clinical studies.
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13
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Marakala V. Neutrophil Gelatinase-Associated Lipocalin (NGAL) in kidney injury- A systematic review. Clin Chim Acta 2022; 536:135-141. [PMID: 36150522 DOI: 10.1016/j.cca.2022.08.029] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/26/2022] [Accepted: 08/30/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND Neutrophil Gelatinase Associated Lipocalin (NGAL) is a secretory protein of neutrophils that can be found both in plasma and urine. Previous works have demonstrated a valuable marker for the early detection of acute kidney injury. In this systematic review, we aimed to assess whether NGAL could be helpful in the diagnosis and prognosis of systemic diseases with kidney involvement. METHODS MEDLINE, PubMed, and EMBASE databases were searched for NGAL, described as a human biomarker for diseases (total: 1690). Specifically, included studies describing the use of NGAL for determining kidney injury outcomes and other conditions associated with kidney dysfunction, including cardiovascular diseases, cardiac surgery, and critically ill systemic disorders. RESULTS A total of 24 validated studies were included in the systemic review after applying the exclusion criteria. In all these studies, NGAL appeared to have a predictive value irrespective of age, from newborn to 78 years. The results indicate that NGAL levels can accurately predict the outcome and severity of acute kidney injury occur in several disease processes, including contrast-induced AKI during cardiac surgery, kidney transplant rejection, chronic heart failure, and systemic inflammation in critically ill patients, even though the significance of NGAL is highly variable across studies. Very high plasma NGAL levels were observed in the patients before the acute rejection of the kidney, indicating the prognostic potential of the NGAL. Specifically, the assays conducted before 72 hrs provided a significant predictive value. CONCLUSION Urinary and serum NGAL appears to be an independent predictor of not only kidney complications but also cardiovascular and liver-related diseases. The kidney is also involved in pathogenesis.
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Affiliation(s)
- Vijaya Marakala
- Department of Basic Medical Sciences, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.
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14
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Burn-Induced Acute Kidney Injury-Two-Lane Road: From Molecular to Clinical Aspects. Int J Mol Sci 2022; 23:ijms23158712. [PMID: 35955846 PMCID: PMC9368898 DOI: 10.3390/ijms23158712] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/19/2022] [Accepted: 08/02/2022] [Indexed: 12/29/2022] Open
Abstract
Severe burn injuries lead to acute kidney injury (AKI) development, increasing the mortality risk up to 28-100%. In addition, there is an increase in hospitalization days and complications appearance. Various factors are responsible for acute or late AKI debut, like hypovolemia, important inflammatory response, excessive load of denatured proteins, sepsis, and severe organic dysfunction. The main measure to improve the prognosis of these patients is rapidly recognizing this condition and reversing the underlying events. For this reason, different renal biomarkers have been studied over the years for early identification of burn-induced AKI, like neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), interleukin-18 (IL-18), and insulin-like growth factor-binding protein 7 (IGFBP7). The fundamental purpose of these studies is to find a way to recognize and prevent acute renal injury progression early in order to decrease the risk of mortality and chronic kidney disease (CKD) onset.
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15
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Cottam D, Azzopardi G, Forni LG. Biomarkers for early detection and predicting outcomes in acute kidney injury. Br J Hosp Med (Lond) 2022; 83:1-11. [DOI: 10.12968/hmed.2022.0032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The current diagnosis of acute kidney injury relies on the measurement of serum creatinine levels and urine output. However, both measures are subject to considerable limitations; for example, change in serum creatinine levels ideally requires a knowledge of baseline function that is often not available. Furthermore, creatinine levels are influenced by many factors including diet, drug therapy, muscle mass, gender and ethnicity, which may lead to underestimation of the extent of renal dysfunction. Similarly, urine output lacks both specificity and sensitivity as a marker of acute kidney injury given that oliguria may be an appropriate physiological response to a multitude of stressors and that output may be maintained until significant renal damage has already occurred. Given the well-documented consequences of acute kidney injury and the considerable burden associated with its development, much attention has focused on early identification of patients at high risk to try and improve outcomes. Many studies have focused on the identification of candidate molecules that may enable the early detection of individuals at risk of developing acute kidney injury, including constitutive proteins associated with kidney damage, as well as molecules upregulated in response to injury, non-renal products that may be filtered, reabsorbed or secreted by the kidney, and markers of renal stress. Such biomarkers may also aid stratification for adverse events, such as the need for kidney replacement therapy or progression to chronic kidney disease and end-stage kidney disease. This article discusses some of these novel biomarkers and assesses the role they may have in the understanding, management, diagnosis and prognostication of acute kidney injury.
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Affiliation(s)
- Daniel Cottam
- Intensive Care Unit, Royal Surrey Hospital Foundation Trust, Guildford, UK
| | - Giada Azzopardi
- South West Thames Renal and Transplantation Unit, Epsom and St Helier University Hospitals, Carshalton, UK
| | - Lui G Forni
- Intensive Care Unit, Royal Surrey Hospital Foundation Trust, Guildford, UK
- Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Surrey, Guildford, UK
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16
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Briguori C, Donahue M, D'Amore C. Renal Insufficiency and the Impact of Contrast Agents. Interv Cardiol 2022. [DOI: 10.1002/9781119697367.ch28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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17
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Nucleic Acid Nanotechnology for Diagnostics and Therapeutics in Acute Kidney Injury. Int J Mol Sci 2022; 23:ijms23063093. [PMID: 35328515 PMCID: PMC8953740 DOI: 10.3390/ijms23063093] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 02/28/2022] [Accepted: 03/09/2022] [Indexed: 02/01/2023] Open
Abstract
Acute kidney injury (AKI) has impacted a heavy burden on global healthcare system with a high morbidity and mortality in both hospitalized and critically ill patients. However, there are still some shortcomings in clinical approaches for the disease to date, appealing for an earlier recognition and specific intervention to improve long-term outcomes. In the past decades, owing to the predictable base-pairing rule and highly modifiable characteristics, nucleic acids have already become significant biomaterials for nanostructure and nanodevice fabrication, which is known as nucleic acid nanotechnology. In particular, its excellent programmability and biocompatibility have further promoted its intersection with medical challenges. Lately, there have been an influx of research connecting nucleic acid nanotechnology with the clinical needs for renal diseases, especially AKI. In this review, we begin with the diagnostics of AKI based on nucleic acid nanotechnology with a highlight on aptamer- and probe-functionalized detection. Then, recently developed nanoscale nucleic acid therapeutics towards AKI will be fully elucidated. Furthermore, the strengths and limitations will be summarized, envisioning a wiser and wider application of nucleic acid nanotechnology in the future of AKI.
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18
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Lupu L, Abukatash H, Banai A, Rozenfeld KL, Lewit D, Merdler I, Loewenstein I, Bornstein G, Banai S, Shacham Y. Relation of Baseline Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels and Contrast-Induced Nephropathy following Percutaneous Coronary Intervention among Chronic Kidney Disease Patients. J Clin Med 2021; 10:jcm10225403. [PMID: 34830685 PMCID: PMC8626017 DOI: 10.3390/jcm10225403] [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: 10/21/2021] [Revised: 11/04/2021] [Accepted: 11/17/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The risk of contrast-induced acute kidney injury (CI-AKI) following coronary intervention is particularly high among patients with chronic kidney disease (CKD). Among these patients, baseline neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular damage, reflects the severity of renal impairment. We evaluated whether the baseline serum NGAL level may be a marker for the development of CI-AKI following percutaneous coronary intervention (PCI). METHODS Eighty-eight CKD patients treated with PCI were included. Serum NGAL levels were drawn upon hospital admission. Receiver operator characteristic (ROC) methods were used to identify the optimal sensitivity and specificity for the observed NGAL level compared with the estimated glomerular filtration rate (eGFR) calculated for patients with CI-AKI. RESULTS Overall CI-AKI incidence was 43%. Baseline serum NGAL levels were significantly higher in patients with CI-AKI than in patients without CI-AKI (150 vs. 103 ng/mL, p < 0.001). According to the ROC curve, baseline NGAL levels performed better than eGFR to predict CI-AKI (AUC 0.753 vs. 0.604), with the optimal cutoff value for baseline NGAL to predict CI-AKI being 127 ng/mL (sensitivity of 68% and specificity of 68%, p < 0.001). In a multivariate logistic regression model, the NGAL level >127 ng/mL ng/mL was independently associated with CI-AKI (HR 9.84, 95% CI: 1.96-40.3; p = 0.01). CONCLUSION Baseline serum NGAL levels in CKD patients may identify a high-risk population for CI-AKI following PCI. Further studies on larger populations are required to validate the potential utility of NGAL measurements in monitoring specific CKD-associated conditions.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Yacov Shacham
- Correspondence: ; Tel.: +972-3-6973222 or +972-52-4262101; Fax: +972-3-6973704
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19
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Al-Amodi HS, Abdelsattar S, Kasemy ZA, Bedair HM, Elbarbary HS, Kamel HFM. Potential Value of TNF-α (-376 G/A) Polymorphism and Cystatin C (CysC) in the Diagnosis of Sepsis Associated Acute Kidney Injury (S-AK I) and Prediction of Mortality in Critically Ill patients. Front Mol Biosci 2021; 8:751299. [PMID: 34692772 PMCID: PMC8526786 DOI: 10.3389/fmolb.2021.751299] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 09/20/2021] [Indexed: 12/29/2022] Open
Abstract
Sepsis Associated Kidney Injury represents a major health concern as it is frequently associated with increased risk of mortality and morbidity. We aimed to evaluate the potential value of TNF-α (-376 G/A) and cystatin C in the diagnosis of S-AKI and prediction of mortality in critically ill patients. This study included 200 critically ill patients and 200 healthy controls. Patients were categorized into 116 with acute septic shock and 84 with sepsis, from which 142 (71%) developed S-AKI. Genotyping of TNF-α (-376 G/A) was performed by RT-PCR and serum CysC was assessed by Enzyme Linked Immunosorbent Assay. Our results showed a highly significant difference in the genotype frequencies of TNF-α (-376 G/A) SNP between S-AKI and non-AKI patients (p < 0.001). Additionally, sCysC levels were significantly higher in the S-AKI group (p = 0.011). The combination of both sCysC and TNF-α (-376 G/A) together had a better diagnostic ability for S-AKI than sCysC alone (AUC = 0.610, 0.838, respectively). Both GA and AA genotypes were independent predictors of S-AKI (p= < 0.001, p = 0.002 respectively). Additionally, sCysC was significantly associated with the risk of S-AKI development (Odds Ratio = 1.111). Both genotypes and sCysC were significant predictors of non-survival (p < 0.001), suggesting their potential role in the diagnosis of S-AKI and prediction of mortality.
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Affiliation(s)
- Hiba S Al-Amodi
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Shimaa Abdelsattar
- Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menoufia University, Shebine Elkoum, Egypt
| | - Zeinab A. Kasemy
- Department of Public Health and Community Medicine, Faculty of Medicine, Menoufia University, Shebine Elkoum, Egypt
| | - Hanan M. Bedair
- Clinical Pathology Department, National Liver Institute, Menoufia University, Shebine Elkoum, Egypt
| | - Hany S. Elbarbary
- Department of Internal Medicine, Renal Unit, Faculty of Medicine, Menoufia University, Shebine Elkoum, Egypt
- Department of Internal Medicine, Renal Unit, Faculty of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Hala F. M. Kamel
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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20
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Lin J, Chen J, Wu D, Li X, Guo X, Shi S, Lin K. Biomarkers for the early prediction of contrast-induced nephropathy after percutaneous coronary intervention in adults: A systematic review and meta-analysis. Angiology 2021; 73:207-217. [PMID: 34461746 DOI: 10.1177/00033197211039921] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Contrast-induced nephropathy (CIN) is a complication of patients undergoing percutaneous coronary intervention (PCI). Promising biomarkers for the early prediction of CIN can significantly improve outcomes of these patients. We searched PubMed, EMBASE, Web of Science, and Cochrane Library for studies. Trials reporting an area under the curve (AUC) for the utility of novel biomarkers in the early prediction of CIN in adults after PCI were included. In total, 42 studies comprising 11,984 adult patients undergoing PCI met the criteria. Four urinary biomarkers and four blood biomarkers were included. For urine biomarkers, the pooled AUCs for neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver-type fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) were 0.91 (95% CI 0.89-0.94), 0.79 (0.75-0.82), 0.78 (0.74-0.82), and 0.79 (0.76-0.83), respectively. The blood biomarkers NGAL, cystatin C, brain natriuretic peptide (BNP), and C-reactive protein (CRP) had pooled AUCs of 0.93 (0.91-0.95), 0.92 (0.89-0.94), 0.78 (0.74-0.81), and 0.75 (0.71-0.79), respectively. Subgroup analysis showed that blood NGAL in early CIN predictive time (<6 h) was more effective in predicting CIN. The efficiency of cystatin C in predicting CIN was reduced, whereas that of L-FABP was increased among chronic kidney disease (CKD) patients.
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Affiliation(s)
- Jing Lin
- 74551Shengli Clinical Medical College of Fujian Medical University, China
| | - Jialong Chen
- 74551Shengli Clinical Medical College of Fujian Medical University, China
| | - Dansen Wu
- 74551Shengli Clinical Medical College of Fujian Medical University, China.,Department of Medical Intensive Care Unit, 117861Fujian Provincial Hospital, China
| | - Xiuhua Li
- 74551Shengli Clinical Medical College of Fujian Medical University, China
| | - Xiaolan Guo
- 74551Shengli Clinical Medical College of Fujian Medical University, China
| | - Songjing Shi
- 74551Shengli Clinical Medical College of Fujian Medical University, China.,Department of Medical Intensive Care Unit, 117861Fujian Provincial Hospital, China
| | - Kaiyang Lin
- 74551Shengli Clinical Medical College of Fujian Medical University, China.,Department of Cardiology, 117861Fujian Provincial Hospital, China
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21
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Oh H, Choi A, Seo N, Lim JS, You JS, Chung YE. Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on post-contrast acute kidney injury. Sci Rep 2021; 11:15625. [PMID: 34341389 PMCID: PMC8329191 DOI: 10.1038/s41598-021-94928-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 07/13/2021] [Indexed: 12/27/2022] Open
Abstract
Post contrast-acute kidney injury (PC-AKI) is defined as the deterioration of renal function after administration of iodinated contrast media. HMGB1 is known to play an important role in the development of acute kidney injury. The purpose of this study was to investigate the association between HMGB1 and PC-AKI and the protective effect of glycyrrhizin, a direct inhibitor of HMGB1, in rats. Rats were divided into three groups: control, PC-AKI and PC-AKI with glycyrrhizin. Oxidative stress was measured with MDA levels and H2DCFDA fluorescence intensity. The mRNA expressions of pro-inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α) and kidney injury markers (KIM-1, NGAL and IL-18) were assessed using RT-PCR and ELISA in kidney tissue. In addition, the serum and intracellular protein levels of HMGB1were analyzed with the enzyme-linked immunosorbent assay (ELISA) and western blotting. Histologic changes were assessed with H&E staining using the transmission electron microscope (TEM). Moreover, serum creatinine (SCr), blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) levels were assessed. Oxidative stress, pro-inflammatory cytokines, kidney injury markers and LDH were significantly higher in PC-AKI compared to the controls, but were lower in PC-AKI with glycyrrhizin. Intracellular and serum HMGB1 levels significantly increased after contrast media exposure, whereas they markedly decreased after glycyrrhizin pretreatment. SCr and BUN also decreased in PC-AKI with glycyrrhizin compared to PC-AKI. In PC-AKI, we could frequently observe tubular dilatation with H&E staining and cytoplasmic vacuoles on TEM, whereas these findings were attenuated in PC-AKI with glycyrrhizin. Our findings indicate that HMGB1 plays an important role in the development of PC-AKI and that glycyrrhizin has a protective effect against renal injury and dysfunction by inhibiting HMGB1 and reducing oxidative stress.
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Affiliation(s)
- Hyewon Oh
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Arom Choi
- Department of Emergency Medicine, Yonsei University College of Medicine, 211 Eonju-Ro, Gangnam-Gu, Seoul, 06273, Republic of Korea
| | - Nieun Seo
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Joon Seok Lim
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Je Sung You
- Department of Emergency Medicine, Yonsei University College of Medicine, 211 Eonju-Ro, Gangnam-Gu, Seoul, 06273, Republic of Korea.
| | - Yong Eun Chung
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
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22
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Rosa VEE, Campos CM, Bacelar A, Abizaid AAC, Mangione JA, Lemos PA, Esteves V, Caramori P, Sampaio RO, Tarasoutchi F, Mehran R, Brito FS. Performance of Prediction Models for Contrast-Induced Acute Kidney Injury after Transcutaneous Aortic Valve Replacement. Cardiorenal Med 2021; 11:166-173. [PMID: 34261063 DOI: 10.1159/000517058] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 04/29/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Acute kidney injury (AKI) has shown to adversely affect outcomes in patients undergoing transcutaneous aortic valve replacement (TAVR), and its correct risk estimation may interfere in procedural planning and strategies. The aim of the study was to test and compare 6 scores in predicting AKI after TAVR. METHODS We tested 6 scores (the contrast material limit score, volume-to-creatinine clearance ratio, ACEF, CR4EATME3AD3, Mehran model A, and Mehran model B) in a total of 559 consecutive patients included in the Brazilian TAVR registry. RESULTS All scores had a poor accuracy and calibration to predict the occurrence of AKI grade 1 or 2. All scores improved the accuracy of AKI risk prediction when stratified for AKI grade 2/3 and AKI grade 3 for all scores. The CR4EATME3AD3 was the best predictor of AKI stage 2/3 (AUC: 0.62; OR: 1.12; 95% CI 1.01-1.26; p = 0.04) and AKI stage 3 (AUC: 0.64; OR: 1.16; 95% CI 1.02-1.32; p = 0.02). Mehran models A and B were both good models for AKI stage 3 (AUC: 0.63; OR: 1.10; 95% CI 1.01-1.22; p = 0.05; and AUC: 0.62; OR: 1.10; 95% CI 1.00-1.21; p = 0.05, respectively). CONCLUSIONS None of the current models demonstrated validity in detecting AKI when its lower grades were evaluated. CR4EATME3AD3 was the best score in predicting moderate to severe AKI after TAVR. These findings suggest that contrast-induced AKI may not be the only factor related to kidney injury after TAVR.
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Affiliation(s)
- Vitor E E Rosa
- Hospital Israelita Albert Einstein, São Paulo, Brazil, .,Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil,
| | - Carlos M Campos
- Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.,Instituto Prevent Senior, São Paulo, Brazil
| | | | | | | | - Pedro A Lemos
- Hospital Israelita Albert Einstein, São Paulo, Brazil.,Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
| | | | | | - Roney O Sampaio
- Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
| | - Flávio Tarasoutchi
- Hospital Israelita Albert Einstein, São Paulo, Brazil.,Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
| | | | - Fabio S Brito
- Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.,Hospital Sírio-Libanês, São Paulo, Brazil
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23
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Yoshihara F, Hosoda H, Doi T, Yoshida M, Kitamura K, Yamamoto H, Asaumi Y, Ishibashi-Ueda H, Kishida M, Arisato T, Matsuo M, Miyazato M, Yasuda S. Combined evaluation of plasma B-type natriuretic peptide and urinary liver-type fatty acid-binding protein/creatinine ratio is related to worsening renal function in patients undergoing elective percutaneous coronary intervention. Clin Exp Nephrol 2021; 25:1319-1328. [PMID: 34255252 DOI: 10.1007/s10157-021-02113-9] [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: 11/11/2020] [Accepted: 07/09/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND There are few reports on the significance for the combined evaluation of blood humoral factors and urinary biomarkers in terms of worsening renal function (WRF) after coronary angiography (CAG)/percutaneous coronary arterial intervention (PCI). METHOD AND RESULTS Urinary liver type-fatty acid-binding protein (L-FABP), neutrophil gelatinase associated lipocalin (NGAL), and adrenomedullin (AM) were measured less than 24 h before and 3 h, 6 h, 1 day, and 2 days after CAG/PCI. WRF was defined as a > 20% decrease in the estimated GFR. WRF occurred in seven of 100 patients and the increase in L-FABP/creatinine (Cr) at 1 day after CAG/PCI was significantly higher in the WRF group than in the non-WRF group. Plasma B-type natriuretic peptide (BNP) before CAG/PCI and L-FABP/Cr at 1 day after CAG/PCI were independent predictors for WRF. The areas under the receiver-operating characteristic curves were as follows: 0.760 for BNP before CAG/PCI, 0.731 for L-FABP/Cr at 1 day after CAG/PCI, and 0.892 for BNP and L-FABP/Cr. Urinary AM levels after PCI/CAG were negatively correlated only to serum potassium levels. Gene expressions of AM and AM-receptor were detectable in renal tubule epithelial cells. AM increased intracellular second messenger levels in a dose-dependent manner. CONCLUSIONS Our results suggest that combined evaluation of plasma BNP and urinary L-FABP/Cr is useful as a predictor of renal dysfunction in CAG/PCI patients.
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Affiliation(s)
- Fumiki Yoshihara
- Division of Nephrology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan.
| | - Hiroshi Hosoda
- Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Takahito Doi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Morikatsu Yoshida
- Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmmachi, Suita, Osaka, 564-8565, Japan
| | - Kazuo Kitamura
- Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Haruko Yamamoto
- Center for Advancing Clinical and Translational Sciences, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Yasuhide Asaumi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Hatsue Ishibashi-Ueda
- Department of Pathology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Masatsugu Kishida
- Division of Nephrology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Tetsuya Arisato
- Division of Nephrology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Miki Matsuo
- Division of Nephrology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Mikiya Miyazato
- Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmmachi, Suita, Osaka, 564-8565, Japan
| | - Satoshi Yasuda
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
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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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Zdziechowska M, Gluba-Brzózka A, Poliwczak AR, Franczyk B, Kidawa M, Zielinska M, Rysz J. Serum NGAL, KIM-1, IL-18, L-FABP: new biomarkers in the diagnostics of acute kidney injury (AKI) following invasive cardiology procedures. Int Urol Nephrol 2020; 52:2135-2143. [PMID: 32557377 PMCID: PMC7575457 DOI: 10.1007/s11255-020-02530-x] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 06/01/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE The aim of this study was to assess the levels of selected markers in patients who underwent planned or emergency coronary angiography and to examine if they correlated with the occurrence of AKI. METHODS The study included 52 patients who underwent planned or emergency coronary angiography and received contrast agent. Serum levels of markers (NGAL, L-FABP, KIM-1, IL-18) were analyzed in all patients using ELISA tests, at baseline, after 24 and 72 h from angiography. RESULTS 9.62% of patients developed CI-AKI. No significant differences were observed between markers levels in patients who developed CI-AKI and those who did not. After 24 h, serum levels of IL-18 were higher in patients with CI-AKI, however, this difference was on the verge of significance. Increase in serum NGAL, KIM-1 and IL-18 was observed after 24 h. Serum levels of biomarkers were insignificantly higher in group with CI-AKI. Significant changes in levels in time (baseline vs. 24 h vs. 72 h) were observed only for NGAL [157.9 (92.4-221.0) vs. 201.8 (156.5-299.9) vs. 118.5 (73.4-198.7); p < 0.0001]. No significant correlations were observed between the decrease in eGFR or the increase in creatinine and biomarkers level. CONCLUSION Obtained results do not allow for the indication of efficient AKI biomarkers. Their further validation in large studies of CI-AKI patients is required.
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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.
| | - Adam R Poliwczak
- Department of Human Physiology, Chair of Experimental and Clinical Physiology, Medical University of Lodz, Lodz, Poland
| | - Beata Franczyk
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Zeromskiego 113, 90-549, Lodz, Poland
| | - Michał Kidawa
- Department of Intensive Cardiac Therapy, Central Teaching Hospital of the Medical University of Lodz, Lodz, Poland
| | - Marzenna Zielinska
- Department of Intensive Cardiac Therapy, Central Teaching Hospital of the Medical University of Lodz, 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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Meraz-Muñoz A, Wald R. Contrast-Associated Acute Kidney Injury: Will Clarifying Mechanisms Allay Anxiety? Clin J Am Soc Nephrol 2020; 15:1225-1227. [PMID: 32841155 PMCID: PMC7480549 DOI: 10.2215/cjn.11960720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Alejandro Meraz-Muñoz
- Division of Nephrology, St. Michael's Hospital and The University of Toronto, Toronto, Ontario, Canada
| | - Ron Wald
- Division of Nephrology, St. Michael's Hospital and The University of Toronto, Toronto, Ontario, Canada .,Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada
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Choi YH, Lee DH, Lee JH. The title: serum neutrophil Gelatinase-associated Lipocalin at 3 hours after return of spontaneous circulation in patients with cardiac arrest and therapeutic hypothermia: early predictor of acute kidney injury. BMC Nephrol 2020; 21:389. [PMID: 32894077 PMCID: PMC7487645 DOI: 10.1186/s12882-020-02054-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 09/02/2020] [Indexed: 03/20/2023] Open
Abstract
Background Serum neutrophil gelatinase-associated lipocalin (NGAL) could be used as a predictive marker of acute kidney injury (AKI) in patients with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) who are managed with targeted temperature management (TTM). However, the NGAL measurement timepoints vary from immediately after ROSC to several days later. The primary objective of this study was to determine an association between AKI and NGAL, both immediately (ROSC-NGAL) and 3 h after ROSC (3 h-NGAL), in OHCA patients with TTM. The secondary objective was to ascertain the association between NGAL levels in the early post-ROSC phase and the neurologic outcomes at discharge. Methods This prospective observational study was conducted between January 2016 and December 2018 and enrolled adult OHCA patients (≥18 years) with TTM after ROSC. The serum NGAL level was measured both immediately and 3 h after ROSC. Univariate and multivariate analyses were performed to identify the associations between AKI, poor neurologic outcome, and NGAL. Results Among 861 OHCA patients, 89 patients were enrolled. AKI occurred in 48 (55.1%) patients. On multivariate logistic regression analysis, 3 h-NGAL was significantly associated with AKI (odds ratio [OR] 1.022; 95% confidence interval [CI] 1.009–1.035; p = 0.001). The area under the receiver operating characteristic curve of 3 h-NGAL for AKI was 0.910 (95% CI 0.830–0.960), and a cut-off value of 178 ng/mL was identified. Both ROSC-NGAL and 3 h-NGAL were not significantly associated with poor neurologic outcome on multivariate logistic regression analysis (ROSC-NGAL; OR 1.017; 95% CI 0.998–1.036; p = 0.084, 3 h-NGAL; OR 0.997; 95% CI 0.992–1.001; p = 0.113). Conclusions The serum NGAL concentration measured 3 h after ROSC is an excellent early predictive marker for AKI in OHCA patients treated with TTM. Future research is needed to identify the optimal measurement timepoint to establish NGAL as a predictor of neurologic outcome and to validate the findings of this research.
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Affiliation(s)
- Yoon Hee Choi
- Department of Emergency Medicine, College of Medicine, Ewha Womans University Mokdong Hospital, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 07985, South Korea
| | - Dong Hoon Lee
- Department of Emergency Medicine, Chung-Ang University, College of Medicine, Seoul, South Korea
| | - Jae Hee Lee
- Department of Emergency Medicine, College of Medicine, Ewha Womans University Mokdong Hospital, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 07985, South Korea.
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He Y, Deng Y, Zhuang K, Li S, Xi J, Chen J. Predictive value of cystatin C and neutrophil gelatinase-associated lipocalin in contrast-induced nephropathy: A meta-analysis. PLoS One 2020; 15:e0230934. [PMID: 32240220 PMCID: PMC7117687 DOI: 10.1371/journal.pone.0230934] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 03/11/2020] [Indexed: 12/21/2022] Open
Abstract
Background There are still limited studies comprehensively examining the diagnostic performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C in contrast-induced nephropathy (CIN). The study aimed to investigate and compare the predictive value of NGAL and cystatin C in the early diagnosis of CIN. Methods and materials We searched the PubMed, EMBASE and Cochrane Library databases until November 10, 2019. The methodological quality of the included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Bivariate modeling and hierarchical summary receiver operating characteristic (HSROC) modeling were performed to summarize and compare the diagnostic performance of blood/urine NGAL and serum cystatin C in CIN. Subgroup and meta-regression analyses were performed according to the study and patient characteristics. Results Thirty-seven studies from thirty-one original studies were included (blood NGAL, 1840 patients in 9 studies; urine NGAL, 1701 patients in 10 studies; serum cystatin C, 5509 patients in 18 studies). Overall, serum cystatin C performed better than serum/urine NGAL (pooled DOR: 43 (95%CI: 12–152); AUROC: 0.93; λ: 3.79); serum and urine NGAL had a similar diagnostic performance (pooled DOR: 25 (95%CI: 6–108)/22(95%CI: 8–64); AUROC: 0.90/0.89; λ: 3.20/3.08). Meta-regression analysis indicated that the sources of heterogeneity might be CIN definition, assays, and nationalities. Conclusion Both NGAL and cystatin C can serve as early diagnostic indicators of CIN, while cystatin C may perform better than NGAL.
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Affiliation(s)
- Yi He
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Yunzhen Deng
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Kaiting Zhuang
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Siyao Li
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Jing Xi
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Junxiang Chen
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- * E-mail:
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Parikh CR, Liu C, Mor MK, Palevsky PM, Kaufman JS, Thiessen Philbrook H, Weisbord SD. Kidney Biomarkers of Injury and Repair as Predictors of Contrast-Associated AKI: A Substudy of the PRESERVE Trial. Am J Kidney Dis 2020; 75:187-194. [PMID: 31547939 PMCID: PMC7012712 DOI: 10.1053/j.ajkd.2019.06.011] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 06/20/2019] [Indexed: 02/07/2023]
Abstract
RATIONALE & OBJECTIVE The PRESERVE trial used a 2 × 2 factorial design to compare intravenous saline solution with intravenous sodium bicarbonate solution and oral N-acetylcysteine with placebo for the prevention of 90-day major adverse kidney events and death (MAKE-D) and contrast-associated acute kidney injury (CA-AKI) among patients with chronic kidney disease undergoing angiography. In this ancillary study, we evaluated the predictive capacities of preangiography injury and repair proteins in urine and plasma for MAKE-D, CA-AKI, and their impact on trial design. STUDY DESIGN Longitudinal analysis. SETTING & PARTICIPANTS A subset of participants from the PRESERVE trial. EXPOSURES Injury (KIM-1, NGAL, and IL-18) and repair (MCP-1, UMOD, and YKL-40) proteins in urine and plasma 1 to 2 hours preangiography. OUTCOMES MAKE-D and CA-AKI. ANALYTICAL APPROACH We analyzed the associations of preangiography biomarkers with MAKE-D and with CA-AKI. We evaluated whether the biomarker levels could enrich the MAKE-D event rate and improve future clinical trial efficiency through an online biomarker prognostic enrichment tool available at prognosticenrichment.com. RESULTS We measured plasma biomarkers in 916 participants and urine biomarkers in 797 participants. After adjusting for urinary albumin-creatinine ratio and baseline estimated glomerular filtration rate, preangiography levels of 4 plasma (KIM-1, NGAL, UMOD, and YKL-40) and 3 urine (NGAL, IL-18, and YKL-40) biomarkers were associated with MAKE-D. Only plasma KIM-1 level was significantly associated with CA-AKI after adjustment. Biomarker levels provided modest discriminatory capacity for MAKE-D. Screening patients using the 50th percentile of preangiography plasma KIM-1 or YKL-40 levels would have reduced the required sample size by 30% (∼2,000 participants). LIMITATIONS Evaluation of prognostic enrichment does not account for changing trial costs, time needed to screen patients, or loss to follow-up. Most participants were male, limiting the generalizability of our findings. CONCLUSIONS Preangiography levels of injury and repair biomarkers modestly predict the development of MAKE-D and can be used to improve the efficiency of future CA-AKI trials.
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Affiliation(s)
- Chirag R Parikh
- Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD.
| | - Caroline Liu
- Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Maria K Mor
- VA Pittsburgh Healthcare System, Pittsburgh, PA; Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA
| | - Paul M Palevsky
- VA Pittsburgh Healthcare System, Pittsburgh, PA; University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - James S Kaufman
- Division of Nephrology, VA New York Harbor Healthcare System and New York University School of Medicine, New York, NY
| | | | - Steven D Weisbord
- VA Pittsburgh Healthcare System, Pittsburgh, PA; University of Pittsburgh School of Medicine, Pittsburgh, PA
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A study of the utility of novel non-invasive urinary and serum biomarkers of blunt kidney injury in a rat model: NGAL, KIM-1, and IL-18. Cent Eur J Immunol 2019; 44:219-225. [PMID: 31871414 PMCID: PMC6925560 DOI: 10.5114/ceji.2019.89592] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2017] [Accepted: 05/08/2017] [Indexed: 12/05/2022] Open
Abstract
This study investigated changes in the concentrations of serum and urine neutrophil gelatinase lipocalin (NGAL), kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18), and cystatin-C (Cys-C) induced by parenchymal and tubular damage following blunt kidney trauma, as well as their potential utility as biomarkers in the detection and follow-up of patients with suspected blunt renal trauma. Three-month-old male Sprague-Dawley rats (n = 18) were divided into three groups (n = 6 in each): group 1: control group (no intervention); group 2: sham group (explorative surgery and exposure of the left kidneys); and group 3: trauma group (explorative surgery and induction of blunt renal trauma of the left kidneys). Serum and urine samples were collected before and 12-24, 36-48, and 60-72 hours later for NGAL, KIM-1, IL-18, and Cys-C measurements. In the trauma group, there was a statistically significant increase in post-operative NGAL, KIM-1, and IL-18 values after 12-24 h and 36-48 h, as compared with pre-operative values. There was also a statistically significant increase in post-operative serum and urine Cys-C values after 60-72 h, as compared with pre-operative values. NGAL, KIM-1, and IL-18 may represent novel non-invasive descriptive candidate biomarkers of early-stage tubular damage in children with renal trauma.
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31
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Effects of remote ischemic conditioning on kidney injury in at-risk patients undergoing elective coronary angiography (PREPARE study): a multicenter, randomized clinical trial. Sci Rep 2019; 9:11985. [PMID: 31427688 PMCID: PMC6700075 DOI: 10.1038/s41598-019-47106-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Accepted: 07/11/2019] [Indexed: 12/22/2022] Open
Abstract
The ability of remote ischemic preconditioning (RIPC) to prevent contrast-induced nephropathy (CIN) following percutaneous coronary angiography in at-risk patients is controversial. No evidence exists regarding potential RIPC positive effects on renal function and clinical outcomes in the long-term. The PREPARE study was a randomized, prospective, multicenter, and double-blinded trial. A total of 222 patients scheduled for coronary angiography and/or percutaneous transluminal coronary angioplasty with an estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m2, or eGFR between 40 and 60 mL/min/1.73 m2 and two further risk factors were allocated to RIPC or control groups. Preventive measures were applied to all patients, including continuous intravenous saline infusion, withdrawal of nephrotoxic drugs, and limited volume of contrast medium. The primary endpoint, namely incidence of CIN, was 3.8% in the control group and 5.1% in the RIPC group (p = 0.74). The secondary endpoints, i.e., changes in serum creatinine and eGFR levels from baseline to 48 hours and from baseline to 12 months following contrast medium exposure, did not differ between both groups. The incidences of all major clinical events at 12 months were similar in both groups. In this population at risk of CIN, preventive strategies were associated with low CIN incidence. RIPC impacted neither the CIN incidence nor both the renal function and clinical outcomes at 1-year follow-up.
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Fiorentino M, Tohme FA, Murugan R, Kellum JA. Plasma Biomarkers in Predicting Renal Recovery from Acute Kidney Injury in Critically Ill Patients. Blood Purif 2019; 48:253-261. [PMID: 31079110 DOI: 10.1159/000500423] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 04/13/2019] [Indexed: 11/19/2022]
Abstract
BACKGROUND Numerous studies have suggested a possible role for acute kidney injury (AKI) biomarkers in predicting renal recovery both before and after renal replacement therapy (RRT). However, definitions for recovery and whether to include patients dying but free of RRT may influence results. OBJECTIVES To validate plasma neutrophil gelatinase-associated lipocalin (pNGAL) as a useful biomarker for predicting or improving the ability of clinical predictors alone to predict recovery following AKI, including in our model plasma B-type natriuretic peptide (pBNP) to account for cardiovascular events. METHODS We analyzed 69 patients enrolled in the Acute Renal Failure Trial Network study. pNGAL and pBNP were measured on days 2, 7, and 14. We analyzed their predictive ability for subsequent recovery, defined as alive and independent from dialysis in 60 days. In sensitivity analyses, we explored changes in results with alternative definitions of recovery. RESULTS Twenty-nine patients (42%) recovered from AKI. Neither pNGAL nor pBNP, alone or in combination, was accurate predictors of renal recovery-the best area under the receiver-operating characteristics curve (AUC) was for pNGAL using the largest relative change (AUC 0.59, 95% CI 0.45-0.74). The best clinical model achieved superior performance to biomarkers (AUC 0.69, 95% CI 0.56-0.81). The AUC was greatest (0.75, 95% CI 0.60-0.91) when pNGAL + pBNP on day 14 were added to the clinical model but this increase did not achieve statistical significance. However, integrated discrimination improvement analysis showed that the addition of pNGAL and pBNP on day 14 to the clinical model significantly improved the prediction of renal recovery (p = 0.008). CONCLUSIONS pNGAL and pBNP can improve the accuracy of clinical parameters in predicting AKI recovery and a full model using biomarkers together with age achieved adequate discrimination.
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Affiliation(s)
- Marco Fiorentino
- The Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari, Bari, Italy
| | - Fadi A Tohme
- The Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Raghavan Murugan
- The Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,The CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - John A Kellum
- The Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA, .,The CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA,
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Abstract
Blood urea nitrogen and serum creatinine are imperfect markers of kidney function because they are influenced by many renal and nonrenal factors independent of kidney function. A biomarker that is released directly into the blood or urine by the kidney in response to injury may be a better early marker of drug-induced kidney toxicity than blood urea nitrogen and serum creatinine. Urine albumin and urine protein, as well as urinary markers kidney injury molecule-1 (KIM-1), β2-microglobulin (B2M), cystatin C, clusterin, and trefoil factor-3 (TFF-3) have been accepted by the Food and Drug Administration and European Medicines Agency as highly sensitive and specific urinary biomarkers to monitor drug-induced kidney injury in preclinical studies and on a case-by-case basis in clinical trials. Other biomarkers of drug-induced kidney toxicity that have been detected in the urine of rodents or patients include IL-18, neutrophil gelatinase-associated lipocalin, netrin-1, liver-type fatty acid-binding protein (L-FABP), urinary exosomes, and TIMP2 (insulin-like growth factor-binding protein 7)/IGFBP7 (insulin-like growth factor-binding protein 7), also known as NephroCheck, the first Food and Drug Administration-approved biomarker testing platform to detect acute kidney injury in patients. In the future, a combined use of functional and damage markers may advance the field of biomarkers of drug-induced kidney toxicity. Earlier detection of drug-induced kidney toxicity with a kidney-specific biomarker may result in the avoidance of nephrotoxic agents in clinical studies and may allow for earlier intervention to repair damaged kidneys.
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Affiliation(s)
- Benjamin R Griffin
- Division of Renal Diseases and Hypertension, University of Colorado at Denver, Aurora, Colorado
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Pletz J, Enoch SJ, Jais DM, Mellor CL, Pawar G, Firman JW, Madden JC, Webb SD, Tagliati CA, Cronin MTD. A critical review of adverse effects to the kidney: mechanisms, data sources, and in silico tools to assist prediction. Expert Opin Drug Metab Toxicol 2018; 14:1225-1253. [PMID: 30345815 DOI: 10.1080/17425255.2018.1539076] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The kidney is a major target for toxicity elicited by pharmaceuticals and environmental pollutants. Standard testing which often does not investigate underlying mechanisms has proven not to be an adequate hazard assessment approach. As such, there is an opportunity for the application of computational approaches that utilize multiscale data based on the Adverse Outcome Pathway (AOP) paradigm, coupled with an understanding of the chemistry underpinning the molecular initiating event (MIE) to provide a deep understanding of how structural fragments of molecules relate to specific mechanisms of nephrotoxicity. Aims covered: The aim of this investigation was to review the current scientific landscape related to computational methods, including mechanistic data, AOPs, publicly available knowledge bases and current in silico models, for the assessment of pharmaceuticals and other chemicals with regard to their potential to elicit nephrotoxicity. A list of over 250 nephrotoxicants enriched with, where possible, mechanistic and AOP-derived understanding was compiled. Expert opinion: Whilst little mechanistic evidence has been translated into AOPs, this review identified a number of data sources of in vitro, in vivo, and human data that may assist in the development of in silico models which in turn may shed light on the interrelationships between nephrotoxicity mechanisms.
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Affiliation(s)
- Julia Pletz
- a School of Pharmacy and Biomolecular Sciences , Liverpool John Moores University , Liverpool , UK
| | - Steven J Enoch
- a School of Pharmacy and Biomolecular Sciences , Liverpool John Moores University , Liverpool , UK
| | - Diviya M Jais
- a School of Pharmacy and Biomolecular Sciences , Liverpool John Moores University , Liverpool , UK
| | - Claire L Mellor
- a School of Pharmacy and Biomolecular Sciences , Liverpool John Moores University , Liverpool , UK
| | - Gopal Pawar
- a School of Pharmacy and Biomolecular Sciences , Liverpool John Moores University , Liverpool , UK
| | - James W Firman
- a School of Pharmacy and Biomolecular Sciences , Liverpool John Moores University , Liverpool , UK
| | - Judith C Madden
- a School of Pharmacy and Biomolecular Sciences , Liverpool John Moores University , Liverpool , UK
| | - Steven D Webb
- b Department of Applied Mathematics , Liverpool John Moores University , Liverpool , UK
| | - Carlos A Tagliati
- c Departamento de Análises Clínicas e Toxicológicas , Universidade Federal de Minas Gerais , Belo Horizonte , Brazil
| | - Mark T D Cronin
- a School of Pharmacy and Biomolecular Sciences , Liverpool John Moores University , Liverpool , UK
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Fiorentino M, Castellano G, Kellum JA. Differences in acute kidney injury ascertainment for clinical and preclinical studies. Nephrol Dial Transplant 2018; 32:1789-1805. [PMID: 28371878 DOI: 10.1093/ndt/gfx002] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Accepted: 01/03/2017] [Indexed: 12/25/2022] Open
Abstract
Background Acute kidney injury (AKI) is a common clinical condition directly associated with adverse outcomes. Several AKI biomarkers have been discovered, but their use in clinical and preclinical studies has not been well examined. This study aims to investigate the differences between clinical and preclinical studies on AKI biomarkers. Methods We performed a systematic review of clinical and preclinical interventional studies that considered AKI biomarkers in enrollment criteria and/or outcome assessment and described the main differences according to their setting, the inclusion of biomarkers in the definition of AKI and the use of biomarkers as primary or secondary end points. Results In the 151 included studies (76 clinical, 75 preclinical), clinical studies have prevalently focused on cardiac surgery (38.1%) and contrast-associated AKI (17.1%), while the majority of preclinical studies have focused on ether ischemia-reperfusion injury or drug-induced AKI (42.6% each). A total of 57.8% of clinical studies defined AKI using the standard criteria and only 19.7% of these studies used AKI biomarkers in the definition of renal injury. Conversely, the majority of preclinical studies defined AKI according to the increase in serum creatinine and blood urea nitrogen, and 32% included biomarkers in that definition. The percentage of both clinical and preclinical studies with biomarkers as a primary end point has not significantly increased in the last 10 years; however, preclinical studies are more likely to use AKI biomarkers as a primary end point compared with clinical studies [odds ratio 2.31 (95% confidence interval 1.17-4.59); P = 0.016]. Conclusion Differences between clinical and preclinical studies are evident and may affect the translation of preclinical findings in the clinical setting.
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Affiliation(s)
- Marco Fiorentino
- Department of Critical Care Medicine, Center for Critical Care Nephrology, CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness) Center, University of Pittsburgh School of Medicine, Pittsburgh, USA.,Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari, Bari, Italy
| | - Giuseppe Castellano
- Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari, Bari, Italy
| | - John A Kellum
- Department of Critical Care Medicine, Center for Critical Care Nephrology, CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness) Center, University of Pittsburgh School of Medicine, Pittsburgh, USA
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Zhu H, Qian Y. Serum neutrophil gelatinase-associated lipocalin and cystatin C are diagnostic markers of renal dysfunction in older patients with coronary artery disease. J Int Med Res 2018; 46:2177-2185. [PMID: 29595358 PMCID: PMC6023060 DOI: 10.1177/0300060517748842] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective This study aimed to assess the diagnostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C for renal dysfunction in older patients with coronary disease. Methods A total of 84 older patients with coronary artery disease were included in this study. Serum NGAL and cystatin C levels were analysed using commercially available kits. Medical data of all patients were recorded and analysed. Results NGAL and cystatin C levels were significantly positively correlated with N-terminal prohormone of brain natriuretic peptide levels and negatively correlated with the estimated glomerular filtration rate. The areas under the receiver operating characteristic curves of serum NGAL and cystatin C levels for diagnosing early renal dysfunction were 0.884 and 0.744, respectively. Conclusion Serum NGAL and cystatin C are potential early and sensitive markers of renal dysfunction in older patients with coronary artery disease.
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Affiliation(s)
- Hong Zhu
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yuying Qian
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China
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Ning L, Li Z, Wei D, Chen H, Yang C, Wu D, Wang Y, Zhang J. Urinary semaphorin 3A as an early biomarker to predict contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention. ACTA ACUST UNITED AC 2018. [PMID: 29513790 PMCID: PMC5856432 DOI: 10.1590/1414-431x20176487] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Contrast-induced acute kidney injury (CI-AKI) is a serious complication of diagnostic coronary angiograph and percutaneous coronary intervention (PCI). However, the exact pathophysiological mechanisms underlying CI-AKI development are largely unknown. The present study examined whether urinary semaphorin 3A levels predict the development of CI-AKI in patients undergoing PCI. This study enrolled 168 patients with stable angina undergoing elective PCI. Serial urine samples, obtained at baseline and 2, 6, 12, 24, 36, and 48 h post-PCI were analyzed by semaphorin 3A and neutrophil gelatinase-associated lipocalin (NGAL) ELISA kit. AKI was defined as an increase in serum creatinine beyond 50% according to the RIFLE classification system. Receiver operator characteristic (ROC) curve analyses identified optimal semaphorin 3A and NGAL values for diagnosing CI-AKI. CI-AKI occurred in 20 of 168 patients. There were no significant differences in the baseline clinical characteristics and angiographic findings between non-AKI patients group and AKI patients group. Both urinary semaphorin 3A and NGAL levels significantly increased at 2 and 6 h post-PCI. ROC analysis showed that the cut-off value of 389.5 pg/mg semaphorin 3A at 2 h post-PCI corresponds to 94% sensitivity and 75% specificity and the cut-off value of 94.4 ng/mg NGAL at 2 h post-PCI corresponds to 74% sensitivity and 82% specificity. Logistic regression showed that semaphorin 3A levels at 2 and 6 h post-PCI were the significant predictors of AKI in our cohort. Urinary semaphorin 3A may be a promising early biomarker for predicting CI-AKI in patients undergoing PCI.
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Affiliation(s)
- Li Ning
- Department of Clinical Laboratory, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Zhiguo Li
- Department of Clinical Laboratory, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Dianjun Wei
- Department of Clinical Laboratory, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Haiyan Chen
- Department of Nephrology, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Chao Yang
- Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi Province, China
| | - Dawei Wu
- Department of Clinical Laboratory, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Yanchun Wang
- Department of Clinical Laboratory, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Jingwei Zhang
- Department of Clinical Laboratory, The Second Hospital of Tianjin Medical University, Tianjin, China
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Connolly M, Kinnin M, McEneaney D, Menown I, Kurth M, Lamont J, Morgan N, Harbinson M. Prediction of contrast induced acute kidney injury using novel biomarkers following contrast coronary angiography. QJM 2018; 111:103-110. [PMID: 29069419 DOI: 10.1093/qjmed/hcx201] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND/INTRODUCTION Chronic kidney disease (CKD) is a risk factor for contrast induced acute kidney injury (CI-AKI). Contrast angiography in CKD patients is a common procedure. Creatinine is a delayed marker of CI-AKI and delays diagnosis which results in significant morbidity and mortality. AIM Early diagnosis of CI-AKI requires validated novel biomarkers. DESIGN A prospective observation study of 301 consecutive CKD patients undergoing coronary angiography was performed. METHODS Samples for plasma neutrophil gelatinase-associated lipocalin (NGAL), serum liver fatty acid-binding protein (L-FABP), serum kidney injury marker 1, serum interleukin 18 and serum creatinine were taken at 0, 1, 2, 4, 6 and 48 h post-contrast. Urinary NGAL and urinary cystatin C were collected at 0, 6 and 48 h. Incidence of major adverse clinical events (MACE) was recorded at 1 year. CI-AKI was defined as an absolute delta rise in creatinine of ≥26.5 µmol/l or a 50% relative rise from baseline at 48 h following contrast. RESULTS CI-AKI occurred in 28 (9.3%) patients. Plasma NGAL was most predictive of CI-AKI at 6 h. L-FABP performed best at 4 h. A combination of Mehran score > 10, 4 h L-FABP and 6 h NGAL improved specificity to 96.7%. MACE was statistically higher at 1 year in CI-AKI patients (25.0 vs. 6.2% in non-CI-AKI patients). DISCUSSION/CONCLUSION Mehran risk score, 4 h serum L-FAPB and 6 h plasma NGAL performed best at early CI-AKI prediction. CI-AKI patients were four times more likely to develop MACE and had a trebling of mortality risk at 1 year.
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Affiliation(s)
- M Connolly
- Cardiovascular Research Unit, Craigavon Cardiac Centre, Southern Trust BT63 5QQ, UK
| | - M Kinnin
- Cardiovascular Research Unit, Craigavon Cardiac Centre, Southern Trust BT63 5QQ, UK
| | - D McEneaney
- Cardiovascular Research Unit, Craigavon Cardiac Centre, Southern Trust BT63 5QQ, UK
| | - I Menown
- Cardiovascular Research Unit, Craigavon Cardiac Centre, Southern Trust BT63 5QQ, UK
| | - M Kurth
- Randox Laboratories Ltd, Crumlin BT29 4QY, UK
| | - J Lamont
- Randox Laboratories Ltd, Crumlin BT29 4QY, UK
| | - N Morgan
- Department of Nephrology, Daisy Hill Hospital, Newry BT35 8DR, UK
| | - M Harbinson
- Centre for Experimental Medicine, Queens University Belfast, Belfast BT7 1NN, UK
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Naito S, Tazaki H, Okamoto T, Takeuchi K, Kan S, Takeuchi Y, Kamata K. Comparison of nephrotoxicity between two gadolinium-contrasts, gadodiamide and gadopentetate in patients with mildly diminished renal failure. J Toxicol Sci 2017; 42:379-384. [PMID: 28496044 DOI: 10.2131/jts.42.379] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
Although gadolinium (Gd)-based contrast media have been found to be nephrotoxic, their nephrotoxicity, and the dependence of nephrotoxicity on chelate types, have not been assessed in patients with normal or mildly diminished renal failure. This prospective, randomized study compared the nephrotoxicity of low doses of the nonionic Gd-based contrast medium gadodiamide (Omniscan®) and the ionic Gd-based contrast medium gadopentetate (Magnevist®) in patients with serum creatinine < 1.6 mg/dL. Patients aged 20 to 80 years, weighing 45 to 70 kg and with normal or < 1.6 mg/dL Serum-creatinine in the 3 months prior to undergoing magnetic resonance imaging (MRI) of brain, were enrolled. Patients were randomized to receive 0.1 mol/kg gadodiamide or gadopentetate. Serum-creatinine, serum cystatin-C, estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula, and estimated creatinine clearance rate (eCCr) using the Cockcroft-Gault formula were measured just before and 16-80 hr after MRI. Groups were compared statistically by Mann-Whitney U-tests and Wilcoxon signed-rank tests. There were no significant differences in clinical characteristics between the gadodiamide (n = 43) and gadopentetate (n = 59) groups. Serum-creatinine, eGFR and eCCr before and 16-80 hr after MRI did not differ significantly within either group or between the two groups. Serum cystatin-C was significantly higher 16-80 hr after than before MRI only in the gadodiamide group (0.79 ± 0.21 vs. 0.74 ± 0.14 mg/L, p = 0.028). The ionic contrast medium, gadopentetate, did not affect renal function during MRI, whereas the nonionic contrast medium, gadodiamide, affected renal function transiently.
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Affiliation(s)
- Shokichi Naito
- Department of Nephrology, Kitasato University School of Medicine
| | - Hiromi Tazaki
- Department of Nephrology, Kitasato University School of Medicine
| | - Tomoko Okamoto
- Department of Nephrology, Kitasato University School of Medicine
| | | | - Shinichi Kan
- Department of Diagnostic Radiology, Kitasato University School of Medicine
| | - Yasuo Takeuchi
- Department of Nephrology, Kitasato University School of Medicine
| | - Kouju Kamata
- Department of Nephrology, Kitasato University School of Medicine.,Sagamiono Medical and Kidney Clinic
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Subclinical Kidney Injury in Children Receiving Nonsteroidal Anti-Inflammatory Drugs After Cardiac Surgery. J Pediatr 2017; 189:175-180. [PMID: 28712521 PMCID: PMC5614821 DOI: 10.1016/j.jpeds.2017.06.045] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 05/19/2017] [Accepted: 06/20/2017] [Indexed: 12/25/2022]
Abstract
OBJECTIVE To investigate the association of nonsteroidal anti-inflammatory drug (NSAID) administration with urinary neutrophil gelatinase-associated lipocalin (NGAL) levels in children following cardiopulmonary bypass (CPB) who did not develop acute kidney injury (AKI). STUDY DESIGN In this prospective observational study, urinary NGAL levels were investigated in 210 children who underwent cardiothoracic surgery requiring CPB. Children with clinical AKI (defined as an increase in serum creatinine ≥50% from baseline within 72 hours of CPB) were excluded from the analysis. NSAIDs were administered no sooner than 24 hours after CPB. NGAL levels were compared between children who received NSAIDs (n = 146) and those who did not receive NSAIDs (n = 64). RESULTS The median age was 3.2 years in the children who received NSAIDs and 2.5 years in those who did not receive NSAIDs (P = .05). Before NSAID administration at 24 hours following CPB, the median NGAL level was 15 ng/mL in both groups (P = .92). Following NSAID administration, the median urinary NGAL level increased to 83 ng/mL (IQR, 45-95 ng/mL) at 72 hours after CPB in those receiving NSAIDs (P < .001). In contrast, the median NGAL level decreased to 10 ng/mL (IQR, 5.4-15.9 ng/mL) at 72 hours after CPB in those who did not receive NSAIDs (P = .01). In multivariable analysis, children receiving NSAIDs demonstrated a 5-fold elevation of urinary NGAL levels at 60-72 hours following CPB compared with those who did not receive NSAIDs (P < .001). CONCLUSION NSAID administration was associated with a significant increase in urinary NGAL in children who did not develop clinical AKI following CPB. This indicates that NGAL can detect NSAID-induced subclinical kidney injury in this population.
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Wybraniec MT, Chudek J, Bożentowicz-Wikarek M, Mizia-Stec K. Prediction of contrast-induced acute kidney injury by early post-procedural analysis of urinary biomarkers and intra-renal Doppler flow indices in patients undergoing coronary angiography. J Interv Cardiol 2017; 30:465-472. [PMID: 28685874 DOI: 10.1111/joic.12404] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Revised: 06/07/2017] [Accepted: 06/09/2017] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The study was designed to evaluate the applicability of combined assessment of urinary biomarkers and intra-renal Doppler flow indices for the prediction of contrast-induced acute kidney injury (CI-AKI) after coronary angiography/percutaneous coronary interventions (CA/PCI). METHODS This prospective observational study covered 95 consecutive patients with coronary artery disease subject to elective or urgent CA/PCI. Doppler intra-renal flow indices were assessed before and 1 h following CA/PCI. Urine samples were collected within 24 h before and 6 h after CA/PCI and assayed for urinary interleukin-18 (IL-18), liver-fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) using ELISA method. CI-AKI was defined as ≥50% relative or ≥0.3 mg/dL absolute increase of serum creatinine concentration at 48 h post-procedurally. RESULTS CI-AKI was confirmed in nine patients (9.5%). CI-AKI onset was associated with significantly higher urinary KIM-1 at 6 h (P = 0.003) and ΔKIM-1 concentrations (P = 0.001), and urinary IL-18 at 6 h (P = 0.014) and ΔIL-18 concentrations (P = 0.012), however, L-FABP and ΔL-FABP levels were comparable in both groups. Receiver operating characteristic curve analysis denoted that post-procedural IL-18 levels at 6 h >89.8 pg/mg (AUC = 0.75, P = 0.007), KIM-1 at 6 h >0.425 ng/mg (AUC = 0.81, P = 0.001), renal resistive index (RRI) at 1 h >0.73 (AUC 0.88; P < 0.0001), and renal pulsatility index (RPI) at 1 h >0.86 (AUC = 0.86; P < 0.0001) predicted CI-AKI onset. Logistic regression analysis of postoperative predictors revealed that IL-18 and RRI were independent predictors of CI-AKI onset (AUC = 0.96; P < 0.0001). CONCLUSIONS Joint assessment of early post-procedural urinary biomarkers and Doppler renovascular parameters aids early diagnosis of CI-AKI in patients undergoing coronary interventions.
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Affiliation(s)
- Maciej T Wybraniec
- First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, Public Hospital No. 7 in Katowice - Upper Silesia Medical Centre, Katowice, Poland
| | - Jerzy Chudek
- Department of Pathophysiology, Medical University of Silesia, Katowice, Poland
| | | | - Katarzyna Mizia-Stec
- First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, Public Hospital No. 7 in Katowice - Upper Silesia Medical Centre, Katowice, Poland
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The role of neutrophil gelatinase-associated lipocalin (NGAL) in the detection of blast lung injury in a military population. J Crit Care 2017; 43:312-315. [PMID: 28985608 DOI: 10.1016/j.jcrc.2017.08.047] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Revised: 06/22/2017] [Accepted: 08/30/2017] [Indexed: 11/22/2022]
Abstract
PURPOSE To study the relationship between serum neutrophil gelatinase-associated lipocalin (NGAL) and military blast and gunshot wound (GSW) to establish whether potential exists for NGAL as a biomarker for blast lung injury (BLI). METHOD Patients from the intensive care unit (ICU) of the Role 3 Medical Treatment Facility at Camp Bastion, Helmand Province, Afghanistan were studied over a five month period commencing in 2012. Age, mechanism, trauma injury severity score (TRISS) and serum NGAL were recorded on ICU admission (NGAL1). Serum NGAL (NGAL2) and PaO2/FiO2 ratio (P/F ratio2) were recorded at 24h. RESULTS 33 patients were injured by blast and 23 by GSW. NGAL1 inversely correlated with TRISS (p=0.020), pH (p=0.002) and P/F ratio 2 (p=0.009) overall. When data was stratified into blast and GSW, NGAL1 also inversely correlated with P/F ratio 2 in the blast injured group (p=0.008) but not GSW group (p=0.27). CONCLUSION Raised NGAL correlated with increased severity of injury (worse survival probability i.e. TRISS and low pH) in both patient groups. There was an inverse correlation between admission NGAL and a marker of blast lung injury (low P/F ratio) at 24h in blast injured group but not GSW group that warrants further investigation.
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Karetnikova V, Osokina A, Gruzdeva O, Uchasova E, Zykov M, Kalaeva V, Kashtalap V, Shafranskaya K, Barbarash O. Serum neutrophil gelatinase-associated lipocalin the estimation of hospital prognosis in patients with ST-elevated myocardial infarction. PLoS One 2017; 12:e0180816. [PMID: 28742104 PMCID: PMC5524370 DOI: 10.1371/journal.pone.0180816] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Accepted: 06/21/2017] [Indexed: 11/19/2022] Open
Abstract
We aimed to assess the clinical significance of serum levels of neutrophil gelatinase-associated lipocalin (sNGAL) for predicting in-hospital outcomes in patients with ST-elevated myocardial infarction (STEMI). Patients admitted within 24 hours of developing STEMI clinical symptoms were evaluated for sNGAL on hospitalization days 1 and 12. Recurrent myocardial infarction, early post-infarction angina, acute cerebrovascular accident, and death were assessed as adverse outcomes during hospitalization. The actors associated with adverse outcome were evaluated using univariate and multivariate regression analysis. Among the 260 STEMI patients included, 32% had ≥1 adverse in-hospital outcome, and significantly higher sNGAL on day 12, (but not on day 1) compared to sNGAL in patients with favorable outcome (p = 0.033). Type-2 diabetes mellitus, age > 60 years, reduced glomerular filtration rate during hospitalization, and high sNGAL on day 12 were identified as risk factors for adverse in-hospital outcome, associated with a 14% increase for each 1-year increment in age after 60 years, and a dramatic increase (3.2 times) for high sNGAL on day 12, with sNGAL ≥ 1.046 ng/ml indicating complicated hospitalization course. sNGAL concentration on the 12th day was associated with the existing adverse outcomes, acting as a marker of MI severity.
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Affiliation(s)
- Victoria Karetnikova
- Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, the Russian Federation
- Federal State Budget Educational Institution of Higher Professional Education “Kemerovo State Medical Academy” the Ministry of Health of the Russian Federation, Kemerovo, the Russian Federation
| | - Anastasia Osokina
- Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, the Russian Federation
- Federal State Budget Educational Institution of Higher Professional Education “Kemerovo State Medical Academy” the Ministry of Health of the Russian Federation, Kemerovo, the Russian Federation
| | - Olga Gruzdeva
- Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, the Russian Federation
| | - Evgenya Uchasova
- Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, the Russian Federation
- * E-mail:
| | - Michael Zykov
- Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, the Russian Federation
| | - Victoria Kalaeva
- Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, the Russian Federation
| | - Vasiliy Kashtalap
- Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, the Russian Federation
- Federal State Budget Educational Institution of Higher Professional Education “Kemerovo State Medical Academy” the Ministry of Health of the Russian Federation, Kemerovo, the Russian Federation
| | - Kristina Shafranskaya
- Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, the Russian Federation
| | - Olga Barbarash
- Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, the Russian Federation
- Federal State Budget Educational Institution of Higher Professional Education “Kemerovo State Medical Academy” the Ministry of Health of the Russian Federation, Kemerovo, the Russian Federation
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Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically Relevant Worsening Renal Function in Acute Heart Failure. Int J Mol Sci 2017; 18:ijms18071470. [PMID: 28698481 PMCID: PMC5535961 DOI: 10.3390/ijms18071470] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2017] [Revised: 06/29/2017] [Accepted: 07/04/2017] [Indexed: 11/21/2022] Open
Abstract
The aim of this study was to evaluate the ability of Neutrophil Gelatinase-Associated Lipocalin (NGAL) to predict clinically relevant worsening renal function (WRF) in acute heart failure (AHF). Plasma NGAL and serum creatinine changes during the first 4 days of admission were investigated in 1447 patients hospitalized for AHF and enrolled in the Placebo-Controlled Randomized Study of the Selective A1Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) study. WRF was defined as serum creatinine rise ≥ 0.3 mg/dL through day 4. Biomarker patterns were described using linear mixed models. WRF developed in 325 patients (22%). Plasma NGAL did not rise earlier than creatinine in patients with WRF. After multivariable adjustment, baseline plasma NGAL, but not creatinine, predicted WRF. AUCs for WRF prediction were modest (<0.60) for all models. NGAL did not independently predict death or rehospitalization (p = n.s.). Patients with WRF and high baseline plasma NGAL had a greater risk of death, and renal or cardiovascular rehospitalization by 60 days than patients with WRF and a low baseline plasma NGAL (p for interaction = 0.024). A rise in plasma NGAL after baseline was associated with a worse outcome in patients with WRF, but not in patients without WRF (p = 0.007). On the basis of these results, plasma NGAL does not provide additional, clinically relevant information about the occurrence of WRF in patients with AHF.
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Yuan Y, Qiu H, Hu X, Luo T, Gao X, Zhao X, Zhang J, Wu Y, Qiao S, Yang Y, Gao R. Predictive value of inflammatory factors on contrast-induced acute kidney injury in patients who underwent an emergency percutaneous coronary intervention. Clin Cardiol 2017; 40:719-725. [PMID: 28543803 DOI: 10.1002/clc.22722] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Revised: 04/11/2017] [Accepted: 04/16/2017] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Contrast-induced acute kidney injury (CI-AKI) is one of the most serious complications in patients who undergo percutaneous coronary intervention (PCI), especially in those with acute coronary syndrome. It has been shown that inflammation may play an important role in the pathophysiology of CI-AKI. HYPOTHESIS Inflammatory factors may play a predominant role in the prediction of CI-AKI in patients who undergo emergency PCI. METHODS Patients who underwent emergency PCI from 2013 to 2015 were consecutively enrolled and were divided into CI-AKI and non-CI-AKI groups. Logistic analysis was used to identify the risk factors of CI-AKI. Receiver operator characteristic curve analysis was performed to evaluate the area under the curve (AUC) and to establish the optimal cutoff. RESULTS A total of 1061 patients were included, and the CI-AKI rate was 5.47% (58/1061). Logistic analysis showed that the white blood cell (WBC) count (odds ratio [OR]: 1.103, 95% confidence interval [CI]: 1.018-1.195, P = 0.016), neutrophil (N) count (OR: 1.134, 95% CI: 1.045-1.232, P = 0.003), neutrophil to lymphocyte ratio (NLR) (OR: 1.105, 95% CI: 1.044-1.169, P = 0.001), C-reactive protein (CRP) level (OR: 1.006, 95% CI: 1.001-1.011, P = 0.020), high-sensitivity C-reactive protein (hs-CRP) level (OR: 1.099, 95% CI: 1.020-1.184, P = 0.013), and big endothelin-1 (ET-1) level (OR: 4.030, 95% CI: 1.989-8.165, P < 0.001) were all significant predictors for CI-AKI, as was the left ventricular ejection fraction and diuretic administration. The AUC of the big ET-1 level was the highest (0.793, 95% CI: 0.733-0.853), followed by the NLR (0.708, 95% CI: 0.641-0.774), hs-CRP level (0.705, 95% CI: 0.627-0.782), CRP level (0.684, 95% CI: 0.607-0.761), N count (0.655, 95% CI: 0.584-0.726), WBC count (0.620, 95% CI: 0.544-0.695), and erythrocyte sedimentation rate (0.611, 95% CI: 0.527-0.695). CONCLUSIONS The WBC count, N count, NLR, CRP level, hs-CRP level, and big ET-1 level are all associated with an increased risk of CI-AKI, and among which, the big ET-1 level, NLR, and the hs-CRP level might have high predictive value for CI-AKI after an emergency PCI.
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Affiliation(s)
- Ying Yuan
- Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Qiu
- Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoying Hu
- Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tong Luo
- Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaojin Gao
- Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xueyan Zhao
- Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Zhang
- Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuan Wu
- Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shubin Qiao
- Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuejin Yang
- Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Runlin Gao
- Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Does NGAL reduce costs? A cost analysis of urine NGAL (uNGAL) & serum creatinine (sCr) for acute kidney injury (AKI) diagnosis. PLoS One 2017; 12:e0178091. [PMID: 28542336 PMCID: PMC5438176 DOI: 10.1371/journal.pone.0178091] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 05/07/2017] [Indexed: 01/24/2023] Open
Abstract
Introduction Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a sensitive and specific diagnostic test for acute kidney injury (AKI) in the Emergency Department (ED), but its economic impact has not been investigated. We hypothesized that uNGAL used in combination with serum creatinine (sCr) would reduce costs in the management of AKI in patients presenting to the ED in comparison to using sCr alone. Materials and methods A cost simulation model was developed for clinical algorithms to diagnose AKI based on sCr alone vs. uNGAL plus sCr (uNGAL+sCr). A cost minimization analysis was performed to determine total expected costs for patients with AKI. uNGAL test characteristics were validated with eight-hundred forty-nine patients with sCr ≥1.5 from a completed study of 1635 patients recruited from EDs at two U.S. hospitals from 2007–8. Biomarker test, AKI work-up, and diagnostic imaging costs were incorporated. Results For a hypothetical cohort of 10,000 patients, the model predicted that the expected costs were $900 per patient (pp) in the sCr arm and $950 in the uNGAL+sCr arm. uNGAL+sCr resulted in 1,578 fewer patients with delayed diagnosis and treatment than sCr alone (2,013 vs. 436 pts) at center 1 and 1,973 fewer patients with delayed diagnosis and treatment than sCr alone at center 2 (2,227 vs. 254 patients). Although initial evaluation costs at each center were $50 pp higher in with uNGAL+sCr, total costs declined by $408 pp at Center 1 and by $522 pp at Center 2 due to expected reduced delays in diagnosis and treatment. Sensitivity analyses confirmed savings with uNGAL + sCr for a range of cost inputs. Discussion Using uNGAL with sCr as a clinical diagnostic test for AKI may improve patient management and reduce expected costs. Any cost savings would likely result from avoiding delays in diagnosis and treatment and from avoidance of unnecessary testing in patients given a false positive AKI diagnosis by use of sCr alone.
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Andreucci M, Faga T, Pisani A, Perticone M, Michael A. The ischemic/nephrotoxic acute kidney injury and the use of renal biomarkers in clinical practice. Eur J Intern Med 2017; 39:1-8. [PMID: 28011057 DOI: 10.1016/j.ejim.2016.12.001] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Revised: 12/02/2016] [Accepted: 12/05/2016] [Indexed: 12/20/2022]
Abstract
The term Acute Renal Failure (ARF) has been replaced by the term Acute Kidney Injury (AKI). AKI indicates an abrupt (within 24-48h) decrease in Glomerular Filtraton Rate, due to renal damage, that causes fluid and metabolic waste retention and alteration of electrolyte and acid-base balance. The renal biomarkers of AKI are substances or processes that are indicators of normal or impaired function of the kidney. The most used renal biomarker is still serum creatinine that is inadequate for several reasons, one of which is its inability to differentiate between hemodynamic changes of renal function ("prerenal azotemia") from intrinsic renal failure or obstructive nephropathy. Cystatin C is no better in this respect. After the description of the pathophysiology of "prerenal azotemia" and of Acute Kidney Injury (AKI) due to ischemia or nephrotoxicity, the renal biomarkers are listed and described: urinary NAG, urinary and serum KIM-1, serum and urinary NGAL, urinary IL-18, urinary L-FABP, serum Midkine, urinary IGFBP7 and TIMP2, urinary α-GST and π-GST, urinary ɣGT and AP, urinary β2M, urinary RBP, serum and urinary miRNA. All have been shown to appear much earlier than the rise of serum Creatinine. Some of them have been demonstrated to predict the clinical outcomes of AKI, such as the need for initiation of dialysis and mortality.
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Affiliation(s)
- Michele Andreucci
- Renal Unit, Department of Health Sciences, "Magna Graecia" University, Catanzaro, Italy.
| | - Teresa Faga
- Renal Unit, Department of Health Sciences, "Magna Graecia" University, Catanzaro, Italy
| | - Antonio Pisani
- Renal Unit, Department of Public Health, "Federico II" University, Naples, Italy
| | - Maria Perticone
- Department of Experimental and Clinical Medicine, "Magna Graecia" University, Catanzaro, Italy
| | - Ashour Michael
- Renal Unit, Department of Health Sciences, "Magna Graecia" University, Catanzaro, Italy
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Niforopoulou P, Iacovidou N, Lelovas P, Karlis G, Papalois Α, Siakavellas S, Spapis V, Kaparos G, Siafaka I, Xanthos T. Correlation of Impedance Threshold Device use during cardiopulmonary resuscitation with post-cardiac arrest Acute Kidney Injury. Am J Emerg Med 2017; 35:846-854. [PMID: 28131602 DOI: 10.1016/j.ajem.2017.01.040] [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: 12/11/2016] [Revised: 01/16/2017] [Accepted: 01/21/2017] [Indexed: 11/28/2022] Open
Abstract
PURPOSE To assess whether use of Impedance Threshold Device (ITD) during cardiopulmonary resuscitation (CPR) reduces the degree of post-cardiac arrest Acute Kidney Injury (AKI), as a result of improved hemodynamics, in a porcine model of ventricular fibrillation (VF) cardiac arrest. METHODS After 8 min of untreated cardiac arrest, the animals were resuscitated either with active compression-decompression (ACD) CPR plus a sham ITD (control group, n=8) or with ACD-CPR plus an active ITD (ITD group, n=8). Adrenaline was administered every 4 min and electrical defibrillation was attempted every 2 min until return of spontaneous circulation (ROSC) or asystole. After ROSC the animals were monitored for 6 h under general anesthesia and then returned to their cages for a 48 h observation, before euthanasia. Two novel biomarkers, Neutrophil Gelatinase-Associated Lipocalin (NGAL) in plasma and Interleukin-18 (IL-18) in urine, were measured at 2 h, 4 h, 6 h, 24 h and 48 h post-ROSC, in order to assess the degree of AKI. RESULTS ROSC was observed in 7 (87.5%) animals treated with the sham valve and 8 (100%) animals treated with the active valve (P=NS). However, more than twice as many animals survived at 48 h in the ITD group (n=8, 100%) compared to the control group (n=3, 37.5%). Urine IL-18 and plasma NGAL levels were augmented post-ROSC in both groups, but they were significantly higher in the control group compared with the ITD group, at all measured time points. CONCLUSION Use of ITD during ACD-CPR improved hemodynamic parameters, increased 48 h survival and decreased the degree of post-cardiac arrest AKI in the resuscitated animals.
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Affiliation(s)
- Panagiota Niforopoulou
- National and Kapodistrian University of Athens, Medical School, 3A Parou st, Melissia, Athens 15127, Greece.
| | - Nicoletta Iacovidou
- National and Kapodistrian University of Athens, Medical School, 3 Pavlou Mela st, Athens 16233, Greece.
| | - Pavlos Lelovas
- National and Kapodistrian University of Athens, Medical School, Laboratory of Research of the Musculoskeletal System, 10 Athinas st, Kifissia, Athens 14561, Greece.
| | - George Karlis
- National and Kapodistrian University of Athens, Medical School, 45-47 Ypsilantou st, Athens 10676, Greece.
| | - Αpostolos Papalois
- Experimental-Research Centre, ELPEN Pharmaceutical Co. Inc., 95 Marathonos Ave, Pikermi, Athens 19009, Greece.
| | - Spyros Siakavellas
- National and Kapodistrian University of Athens, Medical School, Academic Department of Gastroenterology, Laikon General Hospital, 17 Aghiou Thoma st, Athens 11527, Greece.
| | - Vasileios Spapis
- Hippokrateion General Hospital of Athens, 114 Vassilissis Sofias Ave, Athens, 11527, Greece.
| | - George Kaparos
- Aretaieion University Hospital, Biopathology Department, 76 Vassilissis Sofias Ave, Athens 11528, Greece.
| | - Ioanna Siafaka
- National and Kapodistrian University of Athens, Medical School, Aretaieion University Hospital, 76 Vassilissis Sofias Ave, Athens 11528, Greece.
| | - Theodoros Xanthos
- European University of Cyprus, School of Medicine, 6 Diogenis str, Engomi, Nicosia 1516, Cyprus.
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Ashalatha VL, Bitla AR, Kumar VS, Rajasekhar D, Suchitra MM, Lakshmi AY, Rao PVLNS. Biomarker response to contrast administration in diabetic and nondiabetic patients following coronary angiography. Indian J Nephrol 2017; 27:20-27. [PMID: 28182042 PMCID: PMC5255986 DOI: 10.4103/0971-4065.179335] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C represent early renal injury markers for contrast-induced nephropathy (CIN). Baseline parameters such as type and quantity of contrast, patient preparation, renal function status, and diabetes mellitus (DM) are known to affect the response of the kidney to contrast-induced injury. This study was taken up to know the biomarker response to contrast administration in 58 diabetic and 59 nondiabetic male patients with same baseline parameters and baseline serum creatinine <1.2 mg/dl undergoing coronary angiography and their role in predicting the development of CIN. Serum creatinine, serum cystatin C, and urinary-NGAL (u-NGAL) were analyzed at baseline (0 h), 4 h, and 24 h after the administration of contrast medium. CIN was defined as a 25% increase in serum creatinine concentration from the baseline value or an absolute increase of at least 0.5 mg/dl within 48 h after the administration of contrast media. Serum creatinine rose 24 h after contrast administration in the diabetic group compared to 48 h in the nondiabetic group. Serum cystatin C levels rose 24 h after contrast administration in both the groups. The earliest marker to rise in both the groups was u-NGAL at 4 h. Diabetic patients had significantly higher u-NGAL (P = 0.005), and serum creatinine levels (P = 0.008) 4 h, and 24 h after contrast administration, respectively. Serum creatinine and u-NGAL/creatinine at 4 h were found to be the best predictors of CIN in the DM and non-DM patients, respectively. Biomarker response to contrast administration is different in diabetic and nondiabetic patients following contrast administration. Diabetic patients exhibit early and greater degree of renal impairment compared to the nondiabetic patients irrespective of the outcome. We propose the use of serum creatinine in patients with DM and u-NGAL/creatinine in non-DM patients to identify CIN as early as 4 h after contrast administration.
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Affiliation(s)
- V. L. Ashalatha
- Department of Biochemistry, S.V. Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
| | - A. R. Bitla
- Department of Biochemistry, S.V. Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
| | - V. S. Kumar
- Department of Nephrology, S.V. Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
| | - D. Rajasekhar
- Department of Cardiology, S.V. Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
| | - M. M. Suchitra
- Department of Biochemistry, S.V. Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
| | - A. Y. Lakshmi
- Department of Radiology, S.V. Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
| | - P. V. L. N. S. Rao
- Department of Biochemistry, S.V. Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
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