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Saha R, Sharma S, Mondal A, Sati HC, Khan MA, Mahajan S, Datta S, Shalimar, Acharya P. Evaluation of Acute Kidney Injury (AKI) Biomarkers FABP1, NGAL, Cystatin C and IL-18 in an Indian Cohort of Hospitalized Acute-on-chronic Liver Failure (ACLF) Patients. J Clin Exp Hepatol 2025; 15:102491. [PMID: 39901974 PMCID: PMC11787010 DOI: 10.1016/j.jceh.2024.102491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 12/12/2024] [Indexed: 02/05/2025] Open
Abstract
Background/Aims Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis associated with systemic inflammation and organ dysfunction. In ACLF, the development of acute kidney injury (AKI) is associated with poor outcomes. FABP1, NGAL, Cys C and IL-18 have been shown to correlate with ACLF severity and mortality. Hence, our study aimed to evaluate the association of these biomarkers with organ dysfunctions, particularly AKI, in an Indian ACLF patient cohort. Methods 151 study participants including ACLF (n = 91; with AKI n = 63, no-AKI n = 28), non-liver AKI (n = 30) and healthy controls (n = 30) were recruited. Serum ELISA was performed for biomarker estimation. Data interpolation and graphical representation were performed using GraphPad Prism and statistical analyses performed using STATA 14.0. Results FABP1 and Cys C levels were higher in ACLF-AKI patients compared to ACLF no-AKI (P-value ≤ 0.0005). Serum Cys C levels were significantly increased in non-liver AKI compared to ACLF-AKI (P-value ≤ 0.001). AUROC analysis showed better performance of Cys C (AUC 0.79; 95% CI (0.68-0.89)) compared to serum creatinine (AUC 0.71; 95% CI (0.61-0.82)) in discriminating AKI and no-AKI. Correlation analysis revealed positive correlations of FABP1 with creatinine and urea, Cys C with creatinine, urea and OF-Kidney, NGAL, and IL-18 with general markers of organ dysfunction. Plasma MTs) measured in a subset of ACLF patients were elevated in progression-to-AKI. Conclusion Our study showed that in an Indian population of ACLF patients with a high short-term mortality, serum Cys C and FABP1 were elevated in ACLF-AKI, however did not have predictive potential for ACLF-AKI. Cys C levels were significantly higher in non-liver AKI patients vs. ACLF-AKI and correlated with markers of kidney dysfunction whereas NGAL and IL-18 represented higher inflammation and total organ dysfunction. Hence, we conclude that these biomarkers were elevated in ACLF-AKI but did not have predictive potential for AKI in ACLF.
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Affiliation(s)
- Rohini Saha
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | | | | | - Hem C. Sati
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Maroof A. Khan
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Mahajan
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - Sudip Datta
- Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Pragyan Acharya
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
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Ng C, Kim M, Yanti, Kwak MK. Oxidative stress and NRF2 signaling in kidney injury. Toxicol Res 2025; 41:131-147. [PMID: 40013079 PMCID: PMC11850685 DOI: 10.1007/s43188-024-00272-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 11/24/2024] [Accepted: 11/30/2024] [Indexed: 02/28/2025] Open
Abstract
Oxidative stress plays a crucial role in the pathogenesis of acute kidney injury (AKI), chronic kidney disease (CKD), and the AKI-to-CKD transition. This review examines the intricate relationship between oxidative stress and kidney pathophysiology, emphasizing the potential therapeutic role of nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of cellular redox homeostasis. In diverse AKI and CKD models, diminished NRF2 activity exacerbates oxidative stress, whereas genetic and pharmacological NRF2 activation alleviates kidney damage induced by nephrotoxic agents, ischemia-reperfusion injury, fibrotic stimuli, and diabetic nephropathy. The renoprotective effects of NRF2 extend beyond antioxidant defense, encompassing its anti-inflammatory and anti-fibrotic properties. The significance of NRF2 in renal fibrosis is further underscored by its interaction with the transforming growth factor-β signaling cascade. Clinical trials using bardoxolone methyl, a potent NRF2 activator, have yielded both encouraging and challenging outcomes, illustrating the intricacy of modulating NRF2 in human subjects. In summary, this overview suggests the therapeutic potential of targeting NRF2 in kidney disorders and highlights the necessity for continued research to refine treatment approaches.
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Affiliation(s)
- Cherry Ng
- Department of Pharmacy and BK21FOUR Advanced Program for Smart Pharma Leaders, Graduate School of The Catholic University of Korea, Gyeonggi-do, 14662 Republic of Korea
| | - Maxine Kim
- Department of Pharmacy and BK21FOUR Advanced Program for Smart Pharma Leaders, Graduate School of The Catholic University of Korea, Gyeonggi-do, 14662 Republic of Korea
| | - Yanti
- Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta, 12930 Indonesia
| | - Mi-Kyoung Kwak
- Department of Pharmacy and BK21FOUR Advanced Program for Smart Pharma Leaders, Graduate School of The Catholic University of Korea, Gyeonggi-do, 14662 Republic of Korea
- College of Pharmacy, The Catholic University of Korea, 43 Jibong-Ro, Bucheon, Gyeonggi-do 14662 Republic of Korea
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Muğlu H, İnan Kahraman E, Sünger E, Murt A, Bilici A, Görgülü N. Acute Kidney Injury Secondary to Abdominal Compartment Syndrome: Biomarkers, Pressure Variability, and Clinical Outcomes. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:383. [PMID: 40142193 PMCID: PMC11943739 DOI: 10.3390/medicina61030383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Revised: 02/19/2025] [Accepted: 02/21/2025] [Indexed: 03/28/2025]
Abstract
Background and Objectives: Abdominal compartment syndrome (ACS) is a severe clinical condition caused by intra-abdominal hypertension (IAH), often observed in surgical and trauma patients. However, ACS can also develop in non-surgical patients with massive ascites, leading to acute kidney injury (AKI) due to renal hypoperfusion. This study investigates the association between intra-abdominal pressure (IAP) changes, renal biomarkers, and mortality in patients with ACS-related AKI. Materials and Methods: A prospective cohort study was conducted on 24 hospitalized patients with ascites due to malignancy, cirrhosis, or heart failure. IAP was measured via the trans-vesical method on the first and seventh days of hospitalization. Serum and urinary biomarkers, including kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-6 (IL-6), were assessed for their correlation with IAP changes. The primary outcome was in-hospital mortality, and the secondary outcomes included AKI progression and the effect of paracentesis on IAP reduction. Results: The overall in-hospital mortality rate was 50%. Patients who survived had significantly lower IAP on the seventh day compared to those who died (14.9 ± 3.5 mmHg vs. 20.2 ± 5.6 mmHg, p = 0.01). A 25% reduction in IAP was associated with improved kidney function and increased survival (p < 0.001). Urinary KIM-1 and serum NGAL levels showed a moderate correlation with IAP (r = 0.55, p = 0.02 and r = 0.61, p = 0.018, respectively), while IL-6 levels were significantly higher in non-survivors (p = 0.03). Paracentesis was associated with improved survival outcomes (p = 0.04). Conclusions: ACS is a critical but often overlooked cause of AKI in non-surgical patients with massive ascites. Lowering IAP significantly improves renal function and reduces mortality. Urinary KIM-1 and serum NGAL may serve as useful biomarkers for monitoring IAP changes. The early identification and management of IAH through timely interventions such as paracentesis and volume control strategies could improve patient outcomes.
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Affiliation(s)
- Harun Muğlu
- Department of Medical Oncology, Medipol University Faculty of Medicine, Istanbul 34214, Turkey; (E.S.); (A.B.)
| | - Eslem İnan Kahraman
- Department of Internal Medicine, Bagcilar Training and Research Hospital, Istanbul 34200, Turkey;
| | - Erdem Sünger
- Department of Medical Oncology, Medipol University Faculty of Medicine, Istanbul 34214, Turkey; (E.S.); (A.B.)
| | - Ahmet Murt
- Department of Nephrology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey;
| | - Ahmet Bilici
- Department of Medical Oncology, Medipol University Faculty of Medicine, Istanbul 34214, Turkey; (E.S.); (A.B.)
| | - Numan Görgülü
- Department of Nephrology, Bagcilar Training and Research Hospital, Istanbul 34200, Turkey;
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Peng W, Li W, Chai L, Dai Y, Wei Z, Zhan Z. Construction of a sequence activated fluorescence probe for simultaneous detection of γ-glutamyl transpeptidase and peroxynitrite in acute kidney injury. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2025; 325:125066. [PMID: 39216143 DOI: 10.1016/j.saa.2024.125066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/20/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
Acute kidney injury (AKI) can result in a sudden decline in kidney function and, if not promptly diagnosed and treated, can lead to a high mortality rate. Therefore, there is a critical need for the development of a non-invasive and dependable early diagnostic method for AKI to prevent its progression and deterioration. To address the risk of misdiagnosis or overlooked diagnosis due to reliance on a single biomarker, we developed a novel molecular fluorescent probe (HX-GP) to simultaneously detect and image two biomarkers, γ-Glutamyl transpeptidase (γ-GGT) and Peroxynitrite (ONOO-), in the AKI process. HX-GP can specifically detect γ-GGT in the red fluorescence channel (λem = 613 nm) and ONOO- in the green fluorescence channel (λem = 518 nm). HX-GP demonstrated high sensitivity, selectivity, and rapid response, showing excellent biocompatibility and detection performance. In addition, HX-GP was successful in imaging experiments in a cell model of cisplatin-induced AKI, a result that highlights its potential application value in early diagnosis of AKI.
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Affiliation(s)
- Wu Peng
- Department of Respiratory and Critical Care Medicine, Department of Laboratory Medicine, West China School of Nursing/Outpatient Department, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, State Key Laboratory of Respiratory Health and Multimorbidity, Natural and Biomimetic Medicine Research Center, Core Facilities of West China Hospital, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Wenlai Li
- Department of Respiratory and Critical Care Medicine, Department of Laboratory Medicine, West China School of Nursing/Outpatient Department, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, State Key Laboratory of Respiratory Health and Multimorbidity, Natural and Biomimetic Medicine Research Center, Core Facilities of West China Hospital, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Li Chai
- Department of Respiratory and Critical Care Medicine, Department of Laboratory Medicine, West China School of Nursing/Outpatient Department, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, State Key Laboratory of Respiratory Health and Multimorbidity, Natural and Biomimetic Medicine Research Center, Core Facilities of West China Hospital, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yongcheng Dai
- Department of Respiratory and Critical Care Medicine, Department of Laboratory Medicine, West China School of Nursing/Outpatient Department, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, State Key Laboratory of Respiratory Health and Multimorbidity, Natural and Biomimetic Medicine Research Center, Core Facilities of West China Hospital, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Zeliang Wei
- Department of Respiratory and Critical Care Medicine, Department of Laboratory Medicine, West China School of Nursing/Outpatient Department, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, State Key Laboratory of Respiratory Health and Multimorbidity, Natural and Biomimetic Medicine Research Center, Core Facilities of West China Hospital, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
| | - Zixuan Zhan
- Department of Respiratory and Critical Care Medicine, Department of Laboratory Medicine, West China School of Nursing/Outpatient Department, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, State Key Laboratory of Respiratory Health and Multimorbidity, Natural and Biomimetic Medicine Research Center, Core Facilities of West China Hospital, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
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Mendes AFNS, Matela N, Coelho JMP, Marquês JT. A Spectroscopic Methodology to Early Detection of Urinary Tract Infections. SENSORS (BASEL, SWITZERLAND) 2025; 25:400. [PMID: 39860770 PMCID: PMC11768836 DOI: 10.3390/s25020400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/03/2025] [Accepted: 01/08/2025] [Indexed: 01/27/2025]
Abstract
Healthcare-associated infections (HAI) are a critical public health problem, with 30 to 40% of infections related to the urinary tract system. These urinary tract infections (UTIs) are considered one of the most common microbial infections in hospital settings and everyday community contexts, where approximately 80% are highly correlated with urinary catheter insertion, i.e., catheter-associated urinary tract infections (CAUTIs). Considering that 15 to 25% of hospitalised patients need to be catheterised during their treatments and most CAUTIs are asymptomatic, it results in a tremendous challenge to provide an early diagnosis of CAUTI and therefore initiate its treatment. The lack of standardised methods as a first step for urine monitoring and early detection of UTIs is the driving force of this work, which aims to explore the potential of absorption and fluorescence spectroscopic methodologies to detect UTIs. Urine samples were used without any previous treatment to target the most straightforward testing protocol possible. In this work, we successfully developed a powerful methodology that combines ratiometric fluorescence spectroscopy measurements and transmittance at 600 nm to distinguish healthy urine from infected urine. The complementary use of fluorescence spectroscopy and transmittance is what makes the new methodology we propose such a powerful approach to monitor urine samples and provide early detection of UTIs since it provides a quantitative analysis of both healthy and infected urine.
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Affiliation(s)
- Ana F. N. S. Mendes
- Instituto de Biofísica e Engenharia Biomédica (IBEB), Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal; (A.F.N.S.M.); (N.M.); (J.M.P.C.)
| | - Nuno Matela
- Instituto de Biofísica e Engenharia Biomédica (IBEB), Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal; (A.F.N.S.M.); (N.M.); (J.M.P.C.)
| | - João M. P. Coelho
- Instituto de Biofísica e Engenharia Biomédica (IBEB), Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal; (A.F.N.S.M.); (N.M.); (J.M.P.C.)
| | - Joaquim T. Marquês
- Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal
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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: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 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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Booke H, Zarbock A, Meersch M. Renal dysfunction in surgical patients. Curr Opin Crit Care 2024; 30:645-654. [PMID: 39248076 DOI: 10.1097/mcc.0000000000001203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/10/2024]
Abstract
PURPOSE OF REVIEW To provide an overview of the current diagnostic criteria for acute kidney injury (AKI) including their limitations and to discuss prevention and treatment approaches in the perioperative setting. RECENT FINDINGS AKI is common in the perioperative period and is associated with worse short- and long-term outcomes. Current definitions of AKI have several limitations and lead to delayed recognition of kidney dysfunction which is why novel diagnostic approaches by using renal biomarkers may be helpful. In general, prevention of the development and progression of AKI is vital as a causal treatment for AKI is currently not available. Optimization of kidney perfusion and avoidance of nephrotoxic drugs reduce the occurrence of AKI in surgical patients. Angiotensin II as a new vasopressor, the use of remote ischemic preconditioning, and amino acids may be approaches with a positive effect on the kidneys. SUMMARY Evidence suggests that the implementation of supportive measures in patients at high risk for AKI might reduce the occurrence of AKI. Novel biomarkers can help allocating resources by detecting patients at high risk for AKI.
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Affiliation(s)
- Hendrik Booke
- Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, University of Muenster, Muenster, Germany
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Yang Z, Cancio TS, Willis RP, Young MD, Kneifel DM, Salinas J, Meyer AD. An early HMGB1 rise 12 hours before creatinine predicts acute kidney injury and multiple organ failure in a smoke inhalation and burn swine model. Front Immunol 2024; 15:1447597. [PMID: 39534595 PMCID: PMC11554498 DOI: 10.3389/fimmu.2024.1447597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 09/26/2024] [Indexed: 11/16/2024] Open
Abstract
Background Acute kidney injury (AKI) and multiple organ failure (MOF) are leading causes of mortality in trauma injuries. Early diagnosis of AKI and MOF is vital to improve outcomes, but current diagnostic criteria rely on laboratory markers that are delayed or unreliable. In this study, we investigated whether damage associated molecular patterns such as high-mobility group box 1 (HMGB1), syndecan-1 (SDC-1) and C3a correlate with the development of trauma-induced AKI and MOF. Methods Thirty-nine swine underwent smoke inhalation and severe burns, then received critical care for 72 hours or until death. AKI was defined by the KDIGO (Kidney Disease: Improving Global Outcomes) criteria, which labels AKI when a 1.5-fold increase in blood creatinine levels from baseline or a urine output < 0.5 mL/kg/h for 6 hours or more occurs. MOF was defined by the presence of both AKI and acute respiratory distress syndrome (PaO2/FiO2<300 for 4 hours). Results Eight of 39 pigs developed AKI and seven of those developed MOF. Pathological analysis revealed that polytrauma induces significantly higher kidney injury scores compared to sham controls. The average time from injury to KDIGO AKI was 24 hours (interquartile range: 22.50-32.25). Twelve hours after injury, HMGB1 levels were significantly increased in animals that went on to develop AKI compared to those that did not (73.07 ± 18.66 ng/mL vs. 31.64 ± 4.15 ng/mL, p<0.01), as well as in animals that developed MOF compared to those that did not (81.52±19.68 ng/mL vs. 31.19 ± 3.972 ng/mL, p<0.05). SDC-1 and C3a levels were not significantly different at any time point between groups. ROC analysis revealed that HMGB1 levels at 12 hours post-injury were predictive of both AKI and MOF development (AKI: AUROC=0.81, cut-off value=36.41 ng/mL; MOF: AUROC=0.89, cut-off value=36.41 ng/mL). Spearman's correlation revealed that HMGB1 levels at 12 hours correlated with multiple parameters of AKI, including blood urea nitrogen, blood creatinine, and blood myoglobin. Conclusion Twelve-hour post-injury HMGB1 levels predict AKI and MOF in a smoke inhalation and burn swine model. Further research is needed to validate this result in other polytrauma models and in critical combat causalities.
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Affiliation(s)
- Zhangsheng Yang
- Organ Support and Automation Technologies, United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States
| | - Tomas S. Cancio
- Organ Support and Automation Technologies, United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States
| | - Robert P. Willis
- Organ Support and Automation Technologies, United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States
| | - Matthew D. Young
- Organ Support and Automation Technologies, United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States
| | - Dustin M. Kneifel
- Organ Support and Automation Technologies, United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States
| | - Jose Salinas
- Organ Support and Automation Technologies, United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States
| | - Andrew D. Meyer
- Organ Support and Automation Technologies, United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States
- Long School of Medicine, University of Texas Health Science Center, San Antonio, TX, United States
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Jin YW, Ma YR, Liu YT, Yang JR, Zhang MK, Ran FL, Chen Y, Wu XA. Identification of a substrate of the renal tubular transporters for detecting drug-induced early acute kidney injury. Toxicol Sci 2024; 201:190-205. [PMID: 39041788 DOI: 10.1093/toxsci/kfae093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/24/2024] Open
Abstract
Early identification of drug-induced acute kidney injury (AKI) is essential to prevent renal damage. The renal tubules are typically the first to exhibit damage, frequently accompanied by changes in renal tubular transporters. With this in mind, we have identified an endogenous substrate of the renal tubular transporters that may serve as a biomarker for early detection of drug-induced AKI. Using gentamicin- and vancomycin-induced AKI models, we found that traumatic acid (TA), an end metabolite, was rapidly increased in both AKI models. TA, a highly albumin-bound compound (96% to 100%), could not be filtered by the glomerulus and was predominantly eliminated by renal tubules via the OAT1, OAT3, OATP4C1, and P-gp transporters. Importantly, there is a correlation between elevated serum TA levels and reduced OAT1 and OAT3 levels. A clinical study showed that serum TA levels rose before an increase in serum creatinine in 13 out of 20 AKI patients in an intensive care unit setting. In addition, there was a notable rise in TA levels in the serum of individuals suffering from nephrotic syndrome, chronic renal failure, and acute renal failure. These results indicate that the decrease in renal tubular transporter expression during drug-induced AKI leads to an increase in the serum TA level, and the change in TA may serve as a monitor for renal tubular injury. Acute kidney injury (AKI) has a high clinical incidence, and if patients do not receive timely treatment and intervention, it can lead to severe consequences. During AKI, tubular damage is often the primary issue. Endogenous biomarkers of tubular damage are critical for the early diagnosis and treatment of AKI. However, there is currently a lack of reliable endogenous biomarkers for diagnosing tubular damage in clinical practice. Tubular secretion is primarily mediated by renal tubular transporters (channels), which are also impaired during tubular damage. Therefore, we aim to identify endogenous biomarkers of tubular damage from the perspective of renal tubular transporters, providing support for the early detection and intervention of AKI. TA is a substrate of multiple channels, including OAT1, OAT3, OATP4C1, and P-gp, and is primarily secreted by the renal tubules. In the early stages of rat AKI induced by GEN and VCA, serum TA levels are significantly elevated, occurring earlier than the rise in serum creatinine (SCr). Thus, TA is expected to become a potential endogenous biomarker for the early diagnosis of tubular damage.
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Affiliation(s)
- Yong-Wen Jin
- Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China
| | - Yan-Rong Ma
- Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Yu-Ting Liu
- School of Pharmacy, Lanzhou University, Lanzhou 730000, China
| | - Jin-Ru Yang
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China
| | - Ming-Kang Zhang
- School of Pharmacy, Lanzhou University, Lanzhou 730000, China
| | - Feng-Lin Ran
- School of Pharmacy, Lanzhou University, Lanzhou 730000, China
| | - Yang Chen
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China
| | - Xin-An Wu
- Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China
- School of Pharmacy, Lanzhou University, Lanzhou 730000, China
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Stabinska J, Wittsack HJ, Lerman LO, Ljimani A, Sigmund EE. Probing Renal Microstructure and Function with Advanced Diffusion MRI: Concepts, Applications, Challenges, and Future Directions. J Magn Reson Imaging 2024; 60:1259-1277. [PMID: 37991093 PMCID: PMC11117411 DOI: 10.1002/jmri.29127] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 10/26/2023] [Accepted: 10/27/2023] [Indexed: 11/23/2023] Open
Abstract
Diffusion measurements in the kidney are affected not only by renal microstructure but also by physiological processes (i.e., glomerular filtration, water reabsorption, and urine formation). Because of the superposition of passive tissue diffusion, blood perfusion, and tubular pre-urine flow, the limitations of the monoexponential apparent diffusion coefficient (ADC) model in assessing pathophysiological changes in renal tissue are becoming apparent and motivate the development of more advanced diffusion-weighted imaging (DWI) variants. These approaches take advantage of the fact that the length scale probed in DWI measurements can be adjusted by experimental parameters, including diffusion-weighting, diffusion gradient directions and diffusion time. This forms the basis by which advanced DWI models can be used to capture not only passive diffusion effects, but also microcirculation, compartmentalization, tissue anisotropy. In this review, we provide a comprehensive overview of the recent advancements in the field of renal DWI. Following a short introduction on renal structure and physiology, we present the key methodological approaches for the acquisition and analysis of renal DWI data, including intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), non-Gaussian diffusion, and hybrid IVIM-DTI. We then briefly summarize the applications of these methods in chronic kidney disease and renal allograft dysfunction. Finally, we discuss the challenges and potential avenues for further development of renal DWI. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.
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Affiliation(s)
- Julia Stabinska
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA
- Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Hans-Jörg Wittsack
- Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich Heine University Düsseldorf, Dusseldorf, Germany
| | - Lilach O. Lerman
- Division of Nephrology and Hypertension and Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | - Alexandra Ljimani
- Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich Heine University Düsseldorf, Dusseldorf, Germany
| | - Eric E. Sigmund
- Bernard and Irene Schwartz Center for Biomedical Imaging Center for Advanced Imaging Innovation and Research (CAI2R), New York University Langone Health, New York City, New York, USA
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11
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Tentoni N, Hwang M, Villanueva G, Combs R, Lowe J, Ramsey LB, Taylor ZL, Carrillo TM, Aumente MD, López‐Viñau López T, Rizzari C, Howard SC. Early therapeutic drug monitoring of methotrexate and its association with acute kidney injury: A retrospective cohort study. Cancer Med 2024; 13:e70176. [PMID: 39254047 PMCID: PMC11386298 DOI: 10.1002/cam4.70176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 08/16/2024] [Accepted: 08/21/2024] [Indexed: 09/11/2024] Open
Abstract
INTRODUCTION High-dose methotrexate (HDMTX) use can be limited by the development of acute kidney injury (AKI). Early AKI detection is paramount to prevent further renal injury and irreversible toxicities. This study sought to determine whether early elimination patterns of MTX would be useful as a biomarker of AKI in HDMTX treatment. METHODS This retrospective cohort study included two sites that collected ≥2 MTX levels within 16 h from completion of MTX infusion. Early levels were tagged and MTX elimination half-life (t½) were calculated from combinations of two of three different early time periods. Receiver operating characteristic (ROC) curves were synthesized for each elimination t½ (biomarker) with respect to AKI and delayed methotrexate elimination (DME); the biomarker with the highest area under the ROC curve (AUC) was tested in a multiple variable logistic regression model. RESULTS Data from 169 patients who received a total of 556 courses of HDMTX were analyzed. ROC analysis revealed MTX elimination t½ calculated from the second and third time periods had the highest AUC for AKI at 0.62 (interquartile range [IQR] 0.56-0.69) and DME at 0.86 (IQR 0.73-1.00). After adjusting for age, sex, dose (mg/m2), infusion duration, HDMTX course, and baseline estimated glomerular filtration rate, it remained significant for AKI with an OR of 1.29 and 95% confidence interval of 1.03-1.65. CONCLUSION Early MTX elimination t½ measured within 16 h of infusion completion was significantly associated with the development of AKI and serves as an early clearance biomarker that may identify patients who benefit from increased hydration, augmented leucovorin rescue, and glucarpidase administration.
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Affiliation(s)
- Nicolás Tentoni
- Laboratory of Applied Statistics in the Health Sciences, School of MedicineUniversity of Buenos AiresBuenos AiresArgentina
- ResonanceMemphisTennesseeUSA
| | | | | | | | | | - Laura B. Ramsey
- Division of Clinical Pharmacology, Toxicology & Therapeutic InnovationChildren's Mercy HospitalKansas CityMissouriUSA
- Department of PediatricsUniversity of Missouri – Kansas City School of MedicineKansas CityMissouriUSA
| | - Zachary L. Taylor
- Division of Translational and Clinical PharmacologyCincinnati Children's Hospital Medical CenterCincinnatiOhioUSA
- Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical CenterCincinnatiOhioUSA
- Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiOhioUSA
| | | | - María Dolores Aumente
- Pharmacy ServiceReina Sofía University Hospital/Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of CórdobaCórdobaSpain
| | - Teresa López‐Viñau López
- Pharmacy ServiceReina Sofía University Hospital/Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of CórdobaCórdobaSpain
| | - Carmelo Rizzari
- Department of Pediatrics, Pediatric Hematology Oncology UnitUniversity of Milano‐Bicocca, IRCCS San Gerardo dei TintoriMonzaItaly
| | - Scott C. Howard
- ResonanceMemphisTennesseeUSA
- Sant Joan de Déu Hospital BarcelonaBarcelonaSpain
- Yeolyan National Hematology CenterYerevanArmenia
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12
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Chiu LW, Ku YE, Chan FY, Lie WN, Chao HJ, Wang SY, Shen WC, Chen HY. Machine learning algorithms to predict colistin-induced nephrotoxicity from electronic health records in patients with multidrug-resistant Gram-negative infection. Int J Antimicrob Agents 2024; 64:107175. [PMID: 38642812 DOI: 10.1016/j.ijantimicag.2024.107175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 02/29/2024] [Accepted: 04/12/2024] [Indexed: 04/22/2024]
Abstract
OBJECTIVES Colistin-induced nephrotoxicity prolongs hospitalisation and increases mortality. The study aimed to construct machine learning models to predict colistin-induced nephrotoxicity in patients with multidrug-resistant Gram-negative infection. METHODS Patients receiving colistin from three hospitals in the Clinical Research Database were included. Data were divided into a derivation cohort (2011-2017) and a temporal validation cohort (2018-2020). Fifteen machine learning models were established by categorical boosting, light gradient boosting machine and random forest. Classifier performances were compared by the sensitivity, F1 score, Matthews correlation coefficient (MCC), area under the receiver operating characteristic (AUROC) curve, and area under the precision-recall curve (AUPRC). SHapley Additive exPlanations plots were drawn to understand feature importance and interactions. RESULTS The study included 1392 patients, with 360 (36.4%) and 165 (40.9%) experiencing nephrotoxicity in the derivation and temporal validation cohorts, respectively. The categorical boosting with oversampling achieved the highest performance with a sensitivity of 0.860, an F1 score of 0.740, an MCC of 0.533, an AUROC curve of 0.823, and an AUPRC of 0.737. The feature importance demonstrated that the days of colistin use, cumulative dose, daily dose, latest C-reactive protein, and baseline haemoglobin were the most important risk factors, especially for vulnerable patients. A cutoff colistin dose of 4.0 mg/kg body weight/d was identified for patients at higher risk of nephrotoxicity. CONCLUSIONS Machine learning techniques can be an early identification tool to predict colistin-induced nephrotoxicity. The observed interactions suggest a modification in dose adjustment guidelines. Future geographic and prospective validation studies are warranted to strengthen the real-world applicability.
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Affiliation(s)
- Ling-Wan Chiu
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Department of Pharmacy, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
| | - Yi-En Ku
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Fan-Ying Chan
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Wen-Nung Lie
- Department of Electrical Engineering, National Chung Cheng University, Chiayi, Taiwan
| | - Horng-Jiun Chao
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - San-Yuan Wang
- Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Wan-Chen Shen
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Department of Pharmacy, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
| | - Hsiang-Yin Chen
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Department of Pharmacy, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
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13
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Özlü DN, Ekşi M, Şahin S, Kural A, Sipahi M, Kargı T, Bitkin A, Taşçı Aİ. Effect of access sheath diameter used in percutaneous nephrolithotomy on renal function: a prospective randomized study. Urolithiasis 2024; 52:100. [PMID: 38922347 DOI: 10.1007/s00240-024-01582-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Accepted: 05/21/2024] [Indexed: 06/27/2024]
Abstract
We aimed to determine the effect of the access sheath diameter used in percutaneous nephrolithotomy (PNL) on renal function. We also investigated the predictors of impaired renal function. Data were prospectively collected from patients who underwent PNL from December 2020 to December 2021. The patients were randomized into two groups according to access sheath diameter: Group 1 (22 Fr, n = 44) and Group 2 (28 Fr, n = 44). Relative renal function (RRF) was calculated by technetium-99 m dimercaptosuccinic acid scintigraphy, and glomerular filtration rate (GFR) was calculated by diethylenetriamine pentaacetic acid scintigraphy. A difference of 5% or more in RRF was considered a significant functional change. Preoperative and postoperative Kidney Injury Molecule-1 (KIM-1) levels were measured. Preoperative demographic data and stone characteristics were similar between the groups. There were also no statistically significant differences between the groups in terms of scar development, changes in RRF, GFR, or KIM-1/creatinine (Cr) (p > 0.05). Significant deterioration in RRF was detected in a total of six (6.8%) patients, three in each group. The factors predicting loss of function were analyzed by regrouping the patients without loss of function as Group A (n = 82) and those with loss as Group B (n = 6). Only stone volume was statistically significant in multivariate analysis (p = 0.002). Access sheath diameter had no significant effect on renal function after PNL. However, the stone volume was found to independently correlate to a loss of renal function after PNL.
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Affiliation(s)
- Deniz Noyan Özlü
- Department of Urology, University of Health Sciences Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey.
| | - Mithat Ekşi
- Department of Urology, University of Health Sciences Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
| | - Selçuk Şahin
- Department of Urology, University of Health Sciences Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
| | - Alev Kural
- Department of Urology, University of Health Sciences Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
- Department of Biochemistry, University of Health Sciences Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
| | - Murat Sipahi
- Department of Urology, University of Health Sciences Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
- Department of Nuclear Medicine, University of Health Sciences Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
| | - Taner Kargı
- Department of Urology, University of Health Sciences Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
| | - Alper Bitkin
- Department of Urology, University of Health Sciences Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
| | - Ali İhsan Taşçı
- Department of Urology, University of Health Sciences Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
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14
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Leng J, Li L, Tu H, Luo Y, Cao Z, Zhou K, Rizvi SMM, Tie H, Jiang Y. Mechanism and clinical role of TIMP-2 and IGFBP-7 in cardiac surgery-associated acute kidney injury: A review. Medicine (Baltimore) 2024; 103:e38124. [PMID: 38788006 PMCID: PMC11124736 DOI: 10.1097/md.0000000000038124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 04/12/2024] [Indexed: 05/26/2024] Open
Abstract
Acute kidney injury (AKI) is a common postoperative complication, but there is still a lack of accurate biomarkers. Cardiac surgery-associated AKI is the most common cause of major-surgery-related AKI, and patients requiring renal replacement therapy have high mortality rates. Early diagnosis, intervention, and management are crucial for improving patient prognosis. However, diagnosing AKI based solely on changes in serum creatinine level and urine output is insufficient, as these changes often lag behind actual kidney damage, making early detection challenging. Biomarkers such as tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP-7) have been found to be significant predictors of moderate-to-severe AKI when combined with urine content analysis. This article reviews the mechanism of biomarkers TIMP-2 and IGFBP-7 in AKI and provides a comprehensive overview of the clinical effects of TIMP-2 and IGFBP-7 in cardiac surgery-associated AKI, including prediction, diagnosis, and progression.
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Affiliation(s)
- Jiajie Leng
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Letai Li
- Department of anesthesiology, The First College of Clinical Medicine, Chongqing Medical University, Chongqing, China
| | - Hongwen Tu
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yuxiang Luo
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhenrui Cao
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Kun Zhou
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Syed M Musa Rizvi
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hongtao Tie
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yingjiu Jiang
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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15
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Brasileiro-Martins LM, Cavalcante SA, Nascimento TP, Silva-Neto AV, Mariano Santos MD, Camillo-Andrade AC, da Gama Fischer JDS, Ferreira CC, Oliveira LB, Sartim MA, Costa AG, Pucca MB, Wen FH, Moura-da-Silva AM, Sachett J, Carvalho PC, de Aquino PF, Monteiro WM. Urinary proteomics reveals biological processes related to acute kidney injury in Bothrops atrox envenomings. PLoS Negl Trop Dis 2024; 18:e0012072. [PMID: 38536893 PMCID: PMC11020875 DOI: 10.1371/journal.pntd.0012072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 04/16/2024] [Accepted: 03/14/2024] [Indexed: 04/18/2024] Open
Abstract
Acute kidney injury (AKI) is a critical systemic complication caused by Bothrops envenoming, a neglected health problem in the Brazilian Amazon. Understanding the underlying mechanisms leading to AKI is crucial for effectively mitigating the burden of this complication. This study aimed to characterize the urinary protein profile of Bothrops atrox snakebite victims who developed AKI. We analyzed three groups of samples collected on admission: healthy subjects (controls, n = 10), snakebite victims who developed AKI (AKI, n = 10), and those who did not evolve to AKI (No-AKI, n = 10). Using liquid-chromatography tandem mass spectrometry, we identified and quantified (label-free) 1190 proteins. A panel of 65 proteins was identified exclusively in the urine of snakebite victims, with 32 exclusives to the AKI condition. Proteins more abundant or exclusive in AKI's urine were associated with acute phase response, endopeptidase inhibition, complement cascade, and inflammation. Notable proteins include serotransferrin, SERPINA-1, alpha-1B-glycoprotein, and NHL repeat-containing protein 3. Furthermore, evaluating previously reported biomarkers candidates for AKI and renal injury, we found retinol-binding protein, beta-2-microglobulin, cystatin-C, and hepcidin to be significant in cases of AKI induced by Bothrops envenoming. This work sheds light on physiological disturbances caused by Bothrops envenoming, highlighting potential biological processes contributing to AKI. Such insights may aid in better understanding and managing this life-threatening complication.
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Affiliation(s)
- Lisele Maria Brasileiro-Martins
- Department of Research, Dr. Heitor Vieira Dourado Tropical Medicine Foundation, Manaus, Brazil
- School of Health Sciences, Amazonas State University, Manaus, Brazil
| | | | - Thaís Pinto Nascimento
- Department of Research, Dr. Heitor Vieira Dourado Tropical Medicine Foundation, Manaus, Brazil
- School of Health Sciences, Amazonas State University, Manaus, Brazil
- Leonidas and Maria Deane Institute, Oswaldo Cruz Foundation, Manaus, Brazil
| | - Alexandre Vilhena Silva-Neto
- Department of Research, Dr. Heitor Vieira Dourado Tropical Medicine Foundation, Manaus, Brazil
- School of Health Sciences, Amazonas State University, Manaus, Brazil
| | - Marlon Dias Mariano Santos
- Structural and Computational Proteomics Laboratory, Carlos Chagas Institute, Oswaldo Cruz Foundation, Curitiba, Brazil
| | - Amanda C. Camillo-Andrade
- Structural and Computational Proteomics Laboratory, Carlos Chagas Institute, Oswaldo Cruz Foundation, Curitiba, Brazil
| | | | | | | | - Marco Aurelio Sartim
- Department of Research, Dr. Heitor Vieira Dourado Tropical Medicine Foundation, Manaus, Brazil
- School of Health Sciences, Amazonas State University, Manaus, Brazil
- Department of Research, Nilton Lins University, Manaus, Brazil
| | - Allyson Guimarães Costa
- Department of Research, Dr. Heitor Vieira Dourado Tropical Medicine Foundation, Manaus, Brazil
- School of Health Sciences, Amazonas State University, Manaus, Brazil
- Nursing School, Amazonas Federal University, Manaus, Brazil
| | - Manuela B. Pucca
- Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, Brazil
| | - Fan Hui Wen
- Immunopathology Laboratory, Butantan Institute, São Paulo, Brazil
| | | | - Jacqueline Sachett
- Department of Research, Dr. Heitor Vieira Dourado Tropical Medicine Foundation, Manaus, Brazil
- Immunopathology Laboratory, Butantan Institute, São Paulo, Brazil
| | - Paulo Costa Carvalho
- Structural and Computational Proteomics Laboratory, Carlos Chagas Institute, Oswaldo Cruz Foundation, Curitiba, Brazil
| | | | - Wuelton M. Monteiro
- Department of Research, Dr. Heitor Vieira Dourado Tropical Medicine Foundation, Manaus, Brazil
- School of Health Sciences, Amazonas State University, Manaus, Brazil
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16
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Ueno K, Shimozono T, Takahashi Y, Nakae K, Kawamura J, Okamoto Y. Association of albuminuria with kidney function and hemodynamic disturbance in pre-school children who undergo congenital heart disease surgery. Pediatr Nephrol 2024; 39:493-503. [PMID: 37646871 DOI: 10.1007/s00467-023-06130-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 07/22/2023] [Accepted: 08/08/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND We validated the prevalence of albuminuria and its association with kidney function and hemodynamics in pre-school children who underwent surgery for congenital heart disease (CHD). METHODS From 403 patients who had undergone surgery for CHD at least 6 months before pre-school and were admitted to our hospital between 2011 and 2015, 75 who underwent blood and urine tests and cardiac catheterization were included in this study. The urinary albumin-to-creatinine ratio (ACR) was quantified, and the relationship of ACR with physical and laboratory findings and hemodynamics assessed using cardiac catheterization was analyzed. RESULTS The study cohort was divided into three groups: Fontan group (n = 25), tetralogy of Fallot (TOF) group (n = 18), and control group (other biventricular CHDs; n = 32). The median age of patients was 5.9 years. ACR was higher in the Fontan group than in the TOF and control groups (median: 15.0 vs. 5.0 and 0.0 mg/g, p < 0.001). Moreover, albuminuria (ACR > 30 mg/g) was observed in 20.0% of Fontan patients, while ACR was associated with potential complicating factors of Fontan circulation: high central venous pressure, high mean pulmonary artery pressure, and worse than moderate atrioventricular regurgitation. ACR showed a moderate correlation with the cystatin C-based estimated glomerular filtration rate (r = - 0.725, p < 0.001). CONCLUSIONS Measurement of albuminuria in Fontan patients before they join elementary school is useful because it reflects kidney function and hemodynamic factors that can worsen their condition. Identification and management of patients with albuminuria may facilitate early therapeutic intervention for worsening Fontan factors, eventually delaying the deterioration of kidney function. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Kentaro Ueno
- Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
| | - Tsubasa Shimozono
- Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Yoshihiro Takahashi
- Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Koji Nakae
- Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Junpei Kawamura
- Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Yasuhiro Okamoto
- Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
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17
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Zarbock A, Forni LG, Ostermann M, Ronco C, Bagshaw SM, Mehta RL, Bellomo R, Kellum JA. Designing acute kidney injury clinical trials. Nat Rev Nephrol 2024; 20:137-146. [PMID: 37653237 DOI: 10.1038/s41581-023-00758-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/03/2023] [Indexed: 09/02/2023]
Abstract
Acute kidney injury (AKI) is a common clinical condition with various causes and is associated with increased mortality. Despite advances in supportive care, AKI increases not only the risk of premature death compared with the general population but also the risk of developing chronic kidney disease and progressing towards kidney failure. Currently, no specific therapy exists for preventing or treating AKI other than mitigating further injury and supportive care. To address this unmet need, novel therapeutic interventions targeting the underlying pathophysiology must be developed. New and well-designed clinical trials with appropriate end points must be subsequently designed and implemented to test the efficacy of such new interventions. Herein, we discuss predictive and prognostic enrichment strategies for patient selection, as well as primary and secondary end points that can be used in different clinical trial designs (specifically, prevention and treatment trials) to evaluate novel interventions and improve the outcomes of patients at a high risk of AKI or with established AKI.
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Affiliation(s)
- Alexander Zarbock
- Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital of Münster, Münster, Germany.
- Outcomes Research Consortium, Cleveland, OH, USA.
| | - Lui G Forni
- Department of Critical Care, Royal Surrey Hospital Foundation Trust, Guildford, UK
- School of Medicine, Faculty of Health Sciences, University of Surrey, Guildford, UK
| | - Marlies Ostermann
- Department of Intensive Care, King's College London, Guy's & St Thomas' Hospital, London, UK
| | - Claudio Ronco
- Department of Medicine, University of Padova, Padua, Italy
- International Renal Research Institute of Vicenza, Vicenza, Italy
- Department of Nephrology, San Bortolo Hospital, Vicenza, Italy
| | - Sean M Bagshaw
- Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta and Alberta Health Services, Edmonton, Alberta, Canada
| | - Ravindra L Mehta
- Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Rinaldo Bellomo
- Department of Critical Care, University of Melbourne, Parkville, Victoria, Australia
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia
- Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia
- Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - John A Kellum
- The Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
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18
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Yeh TH, Tu KC, Wang HY, Chen JY. From Acute to Chronic: Unraveling the Pathophysiological Mechanisms of the Progression from Acute Kidney Injury to Acute Kidney Disease to Chronic Kidney Disease. Int J Mol Sci 2024; 25:1755. [PMID: 38339031 PMCID: PMC10855633 DOI: 10.3390/ijms25031755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 01/28/2024] [Accepted: 01/30/2024] [Indexed: 02/12/2024] Open
Abstract
This article provides a thorough overview of the biomarkers, pathophysiology, and molecular pathways involved in the transition from acute kidney injury (AKI) and acute kidney disease (AKD) to chronic kidney disease (CKD). It categorizes the biomarkers of AKI into stress, damage, and functional markers, highlighting their importance in early detection, prognosis, and clinical applications. This review also highlights the links between renal injury and the pathophysiological mechanisms underlying AKI and AKD, including renal hypoperfusion, sepsis, nephrotoxicity, and immune responses. In addition, various molecules play pivotal roles in inflammation and hypoxia, triggering maladaptive repair, mitochondrial dysfunction, immune system reactions, and the cellular senescence of renal cells. Key signaling pathways, such as Wnt/β-catenin, TGF-β/SMAD, and Hippo/YAP/TAZ, promote fibrosis and impact renal function. The renin-angiotensin-aldosterone system (RAAS) triggers a cascade leading to renal fibrosis, with aldosterone exacerbating the oxidative stress and cellular changes that promote fibrosis. The clinical evidence suggests that RAS inhibitors may protect against CKD progression, especially post-AKI, though more extensive trials are needed to confirm their full impact.
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Affiliation(s)
- Tzu-Hsuan Yeh
- Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan; (T.-H.Y.); (H.-Y.W.)
| | - Kuan-Chieh Tu
- Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan;
| | - Hsien-Yi Wang
- Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan; (T.-H.Y.); (H.-Y.W.)
- Department of Sport Management, College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan
| | - Jui-Yi Chen
- Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan; (T.-H.Y.); (H.-Y.W.)
- Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan
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19
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Zhang J, Zhao Q, Hu Z. Clinical predictive value of the initial neutrophils to lymphocytes and platelets ratio for prognosis of sepsis patients in the intensive care unit: a retrospective study. Front Med (Lausanne) 2024; 11:1351492. [PMID: 38318247 PMCID: PMC10840849 DOI: 10.3389/fmed.2024.1351492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 01/02/2024] [Indexed: 02/07/2024] Open
Abstract
Background Neutrophils to lymphocytes and platelets (N/LP) ratio has been confirmed as an indirect marker of inflammation. In this study, we aimed to further evaluate the prognostic significance of the N/LP ratio in sepsis patients admitted to the ICU. Methods Sepsis patients from the Affiliated Hospital of Jiangsu University were retrospectively enrolled from January 2015 and July 2023. The primary outcomes were 30/60 days mortality. The secondary outcomes included the incidence of AKI, vasoactive drug, CRRT, invasive ventilation, length of ICU stay, length of hospital stay and ICU mortality. Results A total of 1,066 sepsis patients were enrolled with a median age of 75.0 (66.0, 85.0) years, and 62.5% of them being male. The 30 days and 60 days mortality rates were found to be 28.7 and 34.0%, respectively, while the incidence of AKI was 45.2%. Based on their N/LP ratios, we classified the sepsis patients into three groups: low, middle, and high, consisting of 266, 534, and 266 patients, respectively. According the Cox proportional hazard model, the middle and high N/LP groups were associated with a 1.990/3.106-fold increase in 30 days mortality risk and a 2.066/3.046-fold increase in 60 days mortality risk compared with the low N/LP group. Besides, multivariate logistic regression model suggested that the risk of AKI occurrence increased 2.460 fold in the high group compared to the low group. However, through subgroup analyses, we observed substantial variations in the association between N/LP ratios and 30/60 days mortality rates as well as the incidence of AKI among different populations. Notably, the N/LP ratio measured at ICU admission exhibited a higher AUC for predicting 30/60 days mortality (0.684/0.687). Additionally, we observed a good predictive power for the occurrence of AKI (AUC: 0.645) using the N/LP ratio measured at sepsis prognosis. Regarding the other secondary outcomes, the N/LP ratio was associated with disease severity in sepsis patients, including the need for vasoactive drugs, length of ICU stay, and ICU mortality. Conclusion The N/LP ratio at ICU admission was found to have a significant independent association with 30/60 days mortality and the incidence of AKI in sepsis patients.
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Affiliation(s)
| | | | - Zhenkui Hu
- Department of Critical Care Medicine, The Affiliated Hospital, Jiangsu University, Zhenjiang, China
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20
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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: 6] [Impact Index Per Article: 6.0] [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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21
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Wang B, Wang Y, Wang J, Jin C, Zhou R, Guo J, Zhang H, Wang M. Multiparametric Magnetic Resonance Investigations on Acute and Long-Term Kidney Injury. J Magn Reson Imaging 2024; 59:43-57. [PMID: 37246343 DOI: 10.1002/jmri.28784] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 04/29/2023] [Accepted: 05/01/2023] [Indexed: 05/30/2023] Open
Abstract
Acute kidney injury (AKI) is a frequent complication of critical illness and carries a significant risk of short- and long-term mortality. The prediction of the progression of AKI to long-term injury has been difficult for renal disease treatment. Radiologists are keen for the early detection of transition from AKI to long-term kidney injury, which would help in the preventive measures. The lack of established methods for early detection of long-term kidney injury underscores the pressing needs of advanced imaging technology that reveals microscopic tissue alterations during the progression of AKI. Fueled by recent advances in data acquisition and post-processing methods of magnetic resonance imaging (MRI), multiparametric MRI is showing great potential as a diagnostic tool for many kidney diseases. Multiparametric MRI studies offer a precious opportunity for real-time noninvasive monitoring of pathological development and progression of AKI to long-term injury. It provides insight into renal vasculature and function (arterial spin labeling, intravoxel incoherent motion), tissue oxygenation (blood oxygen level-dependent), tissue injury and fibrosis (diffusion tensor imaging, diffusion kurtosis imaging, T1 and T2 mapping, quantitative susceptibility mapping). The multiparametric MRI approach is highly promising but the longitudinal investigation on the transition of AKI to irreversible long-term impairment is largely ignored. Further optimization and implementation of renal MR methods in clinical practice will enhance our comprehension of not only AKI but chronic kidney diseases. Novel imaging biomarkers for microscopic renal tissue alterations could be discovered and benefit the preventative interventions. This review explores recent MRI applications on acute and long-term kidney injury while addressing lingering challenges, with emphasis on the potential value of the development of multiparametric MRI for renal imaging on clinical systems. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.
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Affiliation(s)
- Bin Wang
- Department of Medical Imaging, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Medical Imaging, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yongfang Wang
- Department of Medical Imaging, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Jing Wang
- Department of Nuclear Medicine and PET Center, The Second Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, China
| | - Chentao Jin
- Department of Nuclear Medicine and PET Center, The Second Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, China
| | - Rui Zhou
- Department of Nuclear Medicine and PET Center, The Second Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, China
| | - Jinxia Guo
- GE Healthcare, MR Research China, Beijing, China
| | - Hong Zhang
- Department of Nuclear Medicine and PET Center, The Second Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, China
- Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, China
- College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China
| | - Min Wang
- Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, China
- College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China
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22
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Lablad Y, Vanhomwegen C, De Prez E, Antoine MH, Hasan S, Baudoux T, Nortier J. Longitudinal Follow-Up of Serum and Urine Biomarkers Indicative of COVID-19-Associated Acute Kidney Injury: Diagnostic and Prognostic Impacts. Int J Mol Sci 2023; 24:16495. [PMID: 38003685 PMCID: PMC10671700 DOI: 10.3390/ijms242216495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 10/30/2023] [Accepted: 11/13/2023] [Indexed: 11/26/2023] Open
Abstract
In patients hospitalized for severe COVID-19, the incidence of acute kidney injury (AKI) is approximately 40%. To predict and understand the implications of this complication, various blood and urine biomarkers have been proposed, including neutrophil gelatinase-associated lipocalin (NGAL), chemokine (C-C motif) ligand 14 (CCL14), cystatin C, leucine aminopeptidase (LAP), and soluble urokinase plasminogen activator (suPAR). This study, conducted between mid-January and early May 2021, aimed to assess the diagnostic and prognostic capabilities of these biomarkers in a cohort of COVID-19 patients monitored during the initial two weeks of hospitalization. Among the 116 patients included in this study, 48 developed AKI within the first three days of hospitalization (41%), with 29 requiring intensive care unit (ICU) admission, and the overall mortality rate was 18%. AKI patients exhibited a statistically significant increase in urinary LAP levels, indicating acute tubular injury as a potential mechanism underlying COVID-19-related renal damage. Conversely, urinary NGAL and CCL-14 excretion rates did not differ significantly between the AKI and non-AKI groups. Importantly, elevated plasma suPAR and cystatin C levels upon admission persisted throughout the first week of hospitalization and were associated with unfavorable outcomes, such as prolonged ICU stays and increased mortality, irrespective of AKI development. In conclusion, this study underscores the early predictive value of urinary LAP levels in identifying acute tubular injury in COVID-19-induced AKI. Moreover, elevated plasma suPAR and cystatin C levels serve as valuable prognostic markers, offering insights into the short-term morbidity and mortality risks among COVID-19 patients, regardless of AKI occurrence. These findings shed light on the complex interplay between COVID-19, renal injury, and biomarkers with diagnostic and prognostic potential.
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Affiliation(s)
- Yahya Lablad
- Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, 1070 Brussels, Belgium; (C.V.); (E.D.P.); (M.-H.A.); (S.H.); (T.B.)
| | - Charlotte Vanhomwegen
- Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, 1070 Brussels, Belgium; (C.V.); (E.D.P.); (M.-H.A.); (S.H.); (T.B.)
| | - Eric De Prez
- Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, 1070 Brussels, Belgium; (C.V.); (E.D.P.); (M.-H.A.); (S.H.); (T.B.)
| | - Marie-Hélène Antoine
- Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, 1070 Brussels, Belgium; (C.V.); (E.D.P.); (M.-H.A.); (S.H.); (T.B.)
| | - Sania Hasan
- Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, 1070 Brussels, Belgium; (C.V.); (E.D.P.); (M.-H.A.); (S.H.); (T.B.)
| | - Thomas Baudoux
- Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, 1070 Brussels, Belgium; (C.V.); (E.D.P.); (M.-H.A.); (S.H.); (T.B.)
- Department of Nephrology, Dialysis and Renal Transplantation, Erasme University Hospital, Erasme Campus, 1070 Brussels, Belgium
| | - Joëlle Nortier
- Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, 1070 Brussels, Belgium; (C.V.); (E.D.P.); (M.-H.A.); (S.H.); (T.B.)
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23
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Chaudhary S, Kashani KB. Acute Kidney Injury Management Strategies Peri-Cardiovascular Interventions. Interv Cardiol Clin 2023; 12:555-572. [PMID: 37673499 DOI: 10.1016/j.iccl.2023.06.008] [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
In many countries, the aging population and the higher incidence of comorbid conditions have resulted in an ever-growing need for cardiac interventions. Acute kidney injury (AKI) is a common complication of these interventions, associated with higher mortalities, chronic or end-stage kidney disease, readmission rates, and hospital and post-discharge costs. The AKI pathophysiology includes contrast-associated AKI, hemodynamic changes, cardiorenal syndrome, and atheroembolism. Preventive measures include limiting contrast media dose, optimizing hemodynamic conditions, and limiting exposure to other nephrotoxins. This review article outlines the current state-of-art knowledge regarding AKI pathophysiology, risk factors, preventive measures, and management strategies in the peri-interventional period.
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Affiliation(s)
- Sanjay Chaudhary
- Department of Critical Care Medicine, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL 32224, USA
| | - Kianoush B Kashani
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
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24
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Chen X, Wang S, Yang J, Wang X, Yang L, Zhou J. The predictive value of hematological inflammatory markers for acute kidney injury and mortality in adults with hemophagocytic Lymphohistiocytosis: A retrospective analysis of 585 patients. Int Immunopharmacol 2023; 122:110564. [PMID: 37451019 DOI: 10.1016/j.intimp.2023.110564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 06/22/2023] [Accepted: 06/22/2023] [Indexed: 07/18/2023]
Abstract
BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological hyperactivation-related disease with a high mortality rate. The purpose of this study was to examine the relationship between complete blood count parameters and the occurrence of acute kidney injury (AKI) and mortality in patients with HLH. METHODS We included 585 adult patients with HLH. Logistic regression models for AKI and 28-day mortality were developed. RESULTS Multivariate logistic regression models revealed that hemoglobin (HB) ≤ 7.3 g/dl (adjusted OR, 1.651; 95% CI, 1.044-2.612), hemoglobin-to-red blood cell distribution width ratio (HRR) < 0.49 (adjusted OR, 1.692), neutrophil-to-lymphocyte ratio (NLR) ≥ 3.15 (adjusted OR, 1.697), and neutrophil-to-lymphocyte-platelet ratio (NLPR) ≥ 11.0 (adjusted OR, 1.608) were independent risk factors for the development of AKI. Moreover, lower platelet levels (31 × 109/L < platelets < 84 × 109/L, adjusted OR, 2.133; platelets ≤ 31 × 109/L, adjusted OR, 3.545) and higher red blood cell distribution width-to-platelet ratio (RPR) levels (0.20 < RPR < 0.54, adjusted OR, 2.595; RPR ≥ 0.54, adjusted OR, 4.307), lymphocytes ≤ 0.34 × 109/L (adjusted OR, 1.793), NLPR ≥ 11.0 (adjusted OR, 2.898), and the aggregate index of systemic inflammation (AISI) ≤ 7 (adjusted OR,1.778) were also independent risk factors for 28-day mortality. Furthermore, patients with AKI had a worse prognosis than those without AKI (P < 0.05). CONCLUSION In patients with HLH, hematological parameters are of great value for the early identification of patients at high risk of AKI and 28-day mortality.
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Affiliation(s)
- Xuelian Chen
- Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China
| | - Siwen Wang
- Department of Occupational Disease and Toxicosis/Nephrology, West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Jia Yang
- Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Wang
- Department of Pediatric Nephrology, West China Second Hospital, Sichuan University, Chengdu, China
| | - Lichuan Yang
- Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China
| | - Jiaojiao Zhou
- Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, China.
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25
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Tabernero G, Pescador M, Ruiz Ferreras E, Morales AI, Prieto M. Evaluation of NAG, NGAL, and KIM-1 as Prognostic Markers of the Initial Evolution of Kidney Transplantation. Diagnostics (Basel) 2023; 13:diagnostics13111843. [PMID: 37296695 DOI: 10.3390/diagnostics13111843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 05/19/2023] [Accepted: 05/23/2023] [Indexed: 06/12/2023] Open
Abstract
Kidney transplantation is the best option for end-stage chronic kidney disease. Transplant viability is conditioned by drugs' nephrotoxicity, ischemia-reperfusion damage, or acute rejection. An approach to improve graft survival is the identification of post-transplant renal function prognostic biomarkers. Our objective was to study three early kidney damage biomarkers (N-acetyl-d-glucosaminidase, NAG; neutrophil gelatinase-associated lipocalin, NGAL; and kidney injury molecule-1, KIM-1) in the initial period after transplantation and to identify possible correlations with main complications. We analysed those biomarkers in urine samples from 70 kidney transplant patients. Samples were taken on days 1, 3, 5, and 7 after intervention, as well as on the day that renal function stabilised (based on serum creatinine). During the first week after transplant, renal function improved based on serum creatinine evolution. However, increasing levels of biomarkers at different times during that first week could indicate tubular damage or other renal pathology. A relationship was found between NGAL values in the first week after transplantation and delayed graft function. In addition, higher NAG and NGAL, and lower KIM-1 values predicted a longer renal function stabilisation time. Therefore, urinary NAG, NGAL, and KIM-1 could constitute a predictive tool for kidney transplant complications, contributing to improve graft survival rates.
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Affiliation(s)
- Guadalupe Tabernero
- Toxicology Unit, Universidad de Salamanca, 37007 Salamanca, Spain
- Department of Nephrology, University Hospital, 37007 Salamanca, Spain
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
| | - Moisés Pescador
- Toxicology Unit, Universidad de Salamanca, 37007 Salamanca, Spain
- Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), 37007 Salamanca, Spain
- RICORS2040-Instituto de Salud Carlos III, 28029 Madrid, Spain
| | | | - Ana I Morales
- Toxicology Unit, Universidad de Salamanca, 37007 Salamanca, Spain
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
- Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), 37007 Salamanca, Spain
- RICORS2040-Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Marta Prieto
- Toxicology Unit, Universidad de Salamanca, 37007 Salamanca, Spain
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
- Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), 37007 Salamanca, Spain
- RICORS2040-Instituto de Salud Carlos III, 28029 Madrid, Spain
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Abuduwupuer Z, Lei Q, Liang S, Xu F, Liang D, Yang X, Liu X, Zeng C. The Spectrum of Biopsy-Proven Kidney Diseases, Causes, and Renal Outcomes in Acute Kidney Injury Patients. Nephron Clin Pract 2023; 147:541-549. [PMID: 37094563 DOI: 10.1159/000530615] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 03/19/2023] [Indexed: 04/26/2023] Open
Abstract
INTRODUCTION Acute kidney injury (AKI) is a group of highly heterogeneous, complicated clinical syndromes. Although kidney biopsy plays an irreplaceable role in evaluating complex AKI, a few studies have focused on the clinicopathology of AKI biopsies. This study analyzed the pathological disease spectrum, causes, and renal outcomes of biopsied AKI patients. METHODS We retrospectively included 2,027 AKI patients who underwent kidney biopsies at a national clinical research center of kidney diseases from 2013 through 2018. To compare the biopsied AKI cases without and with coexisting glomerulopathy, patients were classified into acute tubular/tubulointerstitial nephropathy-associated AKI (ATIN-AKI) and glomerular disease-associated AKI (GD-AKI) groups. RESULTS Of 2,027 biopsied AKI patients, 65.1% were male, with a median age of 43 years. A total of 1,590 (78.4%) patients had coexisting GD, while only 437 (21.6%) patients had ATIN alone. The AKI patients with GD mainly (53.5%) manifested as stage 1 AKI, while most ATIN-AKI patients (74.8%) had stage 3 AKI. In the ATIN-AKI group, 256 (58.6%) patients had acute interstitial nephritis (AIN), and 77 (17.6%) had acute tubular injury (ATI). ATIN-AKI was mainly caused by drugs in 85.5% of AIN and 63.6% of ATI cases, respectively. In AKI patients with coexisting GD, the leading pathological diagnoses in over 80% of patients were IgA nephropathy (IgAN, 22.5%), minimal change disease (MCD, 17.5%), focal segmental glomerulosclerosis (FSGS, 15.3%), lupus nephritis (LN, 11.9%), membranous nephropathy (MN, 10.2%), and ANCA-associated vasculitis (AAV, 4.7%). A total of 775 patients were followed up within 3 months after renal biopsy; ATIN-AKI patients achieved statistically higher complete renal recovery than the GD-AKI patients (83.5% vs. 70.5%, p < 0.001). CONCLUSIONS Most biopsied AKI patients have coexisting GD, while ATIN alone is seen less frequently. ATIN-AKI is mainly caused by drugs. In GD-AKI patients, IgAN, MCD, FSGS, LN, MN, and AAV are the leading diagnoses. Compared to AKI patients without GD, patients with GD suffer from worse renal function recovery.
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Affiliation(s)
- Zulihumaer Abuduwupuer
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Qunjuan Lei
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China
| | - Shaoshan Liang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Feng Xu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Dandan Liang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Xue Yang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Xumeng Liu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Caihong Zeng
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
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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: 13] [Impact Index Per Article: 6.5] [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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28
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Batte A, Kasirye P, Baluku R, Kiguli S, Kalyesubula R, John CC, Schwaderer AL, Imel EA, Conroy AL. Mineral bone disorders and kidney disease in hospitalized children with sickle cell anemia. Front Pediatr 2023; 10:1078853. [PMID: 36819194 PMCID: PMC9932899 DOI: 10.3389/fped.2022.1078853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 12/19/2022] [Indexed: 02/05/2023] Open
Abstract
Background Mineral bone disorders (MBD) are common in sickle cell anemia (SCA). Frequent vaso-occlusive crises (VOC) further impact MBD in children with SCA. We evaluated the prevalence of markers of SCA-related MBD (sMBD) in hospitalized children and assessed the relationship between sMBD and individual mineral abnormalities with kidney disease. Methods We prospectively recruited 185 children with SCA hospitalized with a VOC. Serum measures of mineral bone metabolism (calcium, phosphate, parathyroid hormone, 25-hydroxy vitamin D, FGF23, osteopontin) were measured at enrollment. The primary outcome was markers of sMBD defined as a composite of hypocalcemia, hyperphosphatemia, hyperparathyroidism, or deficiency in 25-OH vitamin D. Secondary outcomes included individual abnormalities in mineral metabolism. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines were used to define SCA-associated acute kidney injury (AKI). AKI was further assessed using urine NGAL as a marker of tubular injury. Acute kidney disease (AKD) was defined as a composite of AKI, an eGFR < 90 ml/min per 1.73 m2 using the Cystatin C GFR equation, or evidence of structural injury (positive biomarker test or albuminuria). Results The mean age of children was 8.9 years and 41.6% were female. The prevalence of sMBD was 47.6%, with hypocalcemia the most frequent abnormality (29.9%, 55/184) followed by hyperphosphatemia (20.7%, 38/184), hyperparathyroidism (8.7%, 16/185), and vitamin D deficiency (5.4%, 10/185). There was no association between sMBD and sKDIGO-defined AKI using serial changes in creatinine or when incorporating biomarkers to define AKI. However, the presence of AKD was associated with a 2.01-fold increased odds of sMBD (95% CI 1.05 to 3.83) and was driven by a decrease in eGFR (OR, 2.90 95% CI: 1.59 to 5.29). When evaluating individual mineral abnormalities, hypocalcemia was associated with AKD and low eGFR while hyperparathyroidism was associated with low eGFR, AKI and structural injury. Vitamin D deficiency was associated with structural kidney injury. Vitamin D deficiency, hyperparathryoidism, and increases in FGF23 and osteopontin predicted mortality (p < 0.05 for all). Conclusion MBD is common among children with SCA hospitalized with VOC. Biomarkers of kidney injury and bone health may help risk stratify children at risk of sMBD. Routine evaluation of sMBD in children with SCA may improve long-term bone health.
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Affiliation(s)
- Anthony Batte
- Child Health and DevelopmentCentre, Makerere University College of Health Sciences, Kampala, Uganda
| | - Philip Kasirye
- Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
| | - Reagan Baluku
- Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
| | - Sarah Kiguli
- Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
| | - Robert Kalyesubula
- Department of Physiology, Makerere University College of Health Sciences, Kampala, Uganda
| | - Chandy C. John
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, United States
- Ryan White Center for Pediatric Infectious Diseases and Global Health, Indianapolis, IN, United States
| | - Andrew L. Schwaderer
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Erik A. Imel
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Andrea L. Conroy
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, United States
- Ryan White Center for Pediatric Infectious Diseases and Global Health, Indianapolis, IN, United States
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Corona A, Cattaneo D, Latronico N. Antibiotic Therapy in the Critically Ill with Acute Renal Failure and Renal Replacement Therapy: A Narrative Review. Antibiotics (Basel) 2022; 11:1769. [PMID: 36551426 PMCID: PMC9774462 DOI: 10.3390/antibiotics11121769] [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: 10/28/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022] Open
Abstract
The outcome for critically ill patients is burdened by a double mortality rate and a longer hospital stay in the case of sepsis or septic shock. The adequate use of antibiotics may impact on the outcome since they may affect the pharmacokinetics (Pk) and pharmacodynamics (Pd) of antibiotics in such patients. Acute renal failure (ARF) occurs in about 50% of septic patients, and the consequent need for continuous renal replacement therapy (CRRT) makes the renal elimination rate of most antibiotics highly variable. Antibiotics doses should be reduced in patients experiencing ARF, in accordance with the glomerular filtration rate (GFR), whereas posology should be increased in the case of CRRT. Since different settings of CRRT may be used, identifying a standard dosage of antibiotics is very difficult, because there is a risk of both oversimplification and failing the therapeutic efficacy. Indeed, it has been seen that, in over 25% of cases, the antibiotic therapy does not reach the necessary concentration target mainly due to lack of the proper minimal inhibitory concentration (MIC) achievement. The aim of this narrative review is to clarify whether shared algorithms exist, allowing them to inform the daily practice in the proper antibiotics posology for critically ill patients undergoing CRRT.
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Affiliation(s)
- Alberto Corona
- Accident & Emergency and Anaesthesia and Intensive Care Medicine Department, Esine and Edolo Hospitals, ASST Valcamonica, 25040 Brescia, Italy
| | - Dario Cattaneo
- Unit of Clinical Pharmacology, ASST Fatebenefratelli Sacco University Hospital, 20157 Milan, Italy
| | - Nicola Latronico
- University Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25100 Brescia, Italy
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30
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Souza E, Muniz F, Costa-Val A, Gomes M, Paes P, Campos M, Peixoto R, Lacerda M, Leme F. Correlation between renal ultrasonography and serum cystatin C in acute kidney disease of critically ill dogs. ARQ BRAS MED VET ZOO 2022. [DOI: 10.1590/1678-4162-12458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
ABSTRACT Acute kidney injury (AKI) is defined as the rapid decline in kidney function. Its development is related to critical clinical statuses, such as sepsis, complicated post-surgical recovery, and infectious diseases. Serum cystatin C (CysC) has the best correlation with the glomerular filtration rate. Ultrasonography stands out because it is highly accessible and can be done at the bedside. Twenty-eight dogs admitted to the intensive care unit with serum creatinine values <1.6 mg/dL and at-risk factors of AKI development were selected. CysC measurements and ultrasound assessments were performed daily for 72 hours. Using CysC dosage, 22/28 animals (78.6%) were considered to have AKI, and 17/22 had ultrasound compatible with AKI changes, demonstrating moderate agreement with CysC dosage. Increased cortical renal echogenicity is the most prevalent alteration in critically ill patients and is correlated with serum increases in CysC and is associated with renal structural damage.
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Affiliation(s)
- E.M. Souza
- Universidade Federal de Minas Gerais, Brazil
| | - F.S. Muniz
- Universidade Federal de Minas Gerais, Brazil
| | | | - M.G. Gomes
- Universidade Federal de Minas Gerais, Brazil
| | - P.R.O. Paes
- Universidade Federal de Minas Gerais, Brazil
| | | | | | | | - F.O.P. Leme
- Universidade Federal de Minas Gerais, Brazil
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31
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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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Kuo J, Akison LK, Chatfield MD, Trnka P, Moritz KM. Serum and urinary biomarkers to predict acute kidney injury in premature infants: a systematic review and meta-analysis of diagnostic accuracy. J Nephrol 2022; 35:2001-2014. [PMID: 35384606 PMCID: PMC9584850 DOI: 10.1007/s40620-022-01307-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 03/05/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND Premature infants are at high risk for acute kidney injury (AKI) and current diagnostic criteria are flawed. The objective of this study was to determine the diagnostic accuracy of urine and serum biomarkers not currently used in routine clinical practice to predict AKI in premature infants. METHOD A systematic review was performed that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA). Data were extracted on the diagnostic accuracy of AKI biomarkers using serum creatinine or urine output as the reference standard. Quality and validity were assessed using modified Standards for Reporting Diagnostic Accuracy (STARD) criteria. RESULTS We identified 1024 articles, with 15 studies (791 infants) eligible for inclusion. Twenty-seven biomarkers were identified including serum cystatin C and urinary neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin, kidney injury molecule-1, epidermal growth factor, and protein S100-P. However, many were only reported by one study each. A meta-analysis could only be conducted on uNGAL (288 infants from 6 studies) using a hierarchical, random-effects logistic-regression model. uNGAL had a summary sensitivity of 77% (95% CI 58-89%), specificity of 76% (95% CI 57-88%) and AUC-SROC of 0.83 (95% CI 0.80-0.86) for the diagnosis of AKI. By utilising uNGAL, the post-test probability of AKI increased to 52% (95% CI 37-66%) with a positive test and decreased to 9% (95% CI 5-16%) with a negative test if the pre-test probability was 25%. CONCLUSION uNGAL shows promise as a diagnostically accurate biomarker for AKI in premature infants.
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Affiliation(s)
- Jenny Kuo
- Child Health Research Centre, The University of Queensland, South Brisbane, QLD, Australia
| | - Lisa K Akison
- Child Health Research Centre, The University of Queensland, South Brisbane, QLD, Australia.,School of Biomedical Sciences, The University of Queensland, Sir William MacGregor Building, St Lucia, QLD, 4072, Australia
| | - Mark D Chatfield
- Child Health Research Centre, The University of Queensland, South Brisbane, QLD, Australia
| | - Peter Trnka
- Child Health Research Centre, The University of Queensland, South Brisbane, QLD, Australia.,Queensland Child and Adolescent Renal Service, Queensland Children's Hospital, South Brisbane, QLD, Australia
| | - Karen M Moritz
- Child Health Research Centre, The University of Queensland, South Brisbane, QLD, Australia. .,School of Biomedical Sciences, The University of Queensland, Sir William MacGregor Building, St Lucia, QLD, 4072, Australia.
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Lombardi M, Molisana M, Genovesi E, De Innocentiis C, Limbruno U, Misuraca L, Moretti L, Di Vito L, Renda G, Zimarino M, Di Nicola M, De Caterina R. Urine alkalinisation to prevent contrast-induced acute kidney injury: the prospective, randomised, controlled, open-label TEATE trial. EUROINTERVENTION 2022; 18:562-573. [PMID: 35620986 DOI: 10.4244/eij-d-22-00010] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Contrast-induced acute kidney injury (CI-AKI) is prognostically relevant in invasive cardiological and radiological procedures. The administration of sodium bicarbonate has controversial effects. It has been hypothesised that bicarbonate is ineffective when unable to achieve adequate urine alkalinisation. AIMS We tested the hypothesis that alkaline urine status with oral or intravenous (i.v.) bicarbonate on top of hydration alone prevents CI-AKI. METHODS In a prospective, randomised, parallel-group, open-label trial, we compared 1) saline hydration alone (n=81); 2) i.v. bicarbonate (n=82); and 3) oral bicarbonate (n=78), in patients with chronic kidney disease (CKD) scheduled for the intra-arterial administration of contrast medium. The primary endpoint was the incidence of CI-AKI according to alkaline urine status achieved immediately before angiography. Secondary endpoints were the mean change of urine pH up to the time of angiography and the incidence of CI-AKI in the three groups. RESULTS The incidence of CI-AKI was not significantly different in the three treatment arms (20% in the hydration group, 21% in the oral bicarbonate group and 22% in the i.v. bicarbonate group; p=0.94). Patients achieving a pH >6 before angiography (n=145) had a significantly lower incidence of CI-AKI compared with the others (n=96; odds ratio [OR] 0.48, 95% confidence interval [CI]: 0.25-0.90; p=0.023, primary study hypothesis). The proportion of patients achieving a pH >6 was higher in the i.v. and oral bicarbonate groups compared with hydration alone. CONCLUSIONS Urinary pH before administration of contrast medium is an inverse correlate of CI-AKI incidence, and bicarbonate is superior to hydration alone in achieving urinary alkalinisation. Since, however, bicarbonate did not reduce the incidence of CI-AKI, we conclude that urinary pH is a marker and not a mediator of CI-AKI (ClinicalTrials.gov: NCT02980003).
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Affiliation(s)
- Marco Lombardi
- Institute of Cardiology, G. d'Annunzio University, Chieti, Italy
| | - Michela Molisana
- Institute of Cardiology, G. d'Annunzio University, Chieti, Italy
| | - Eugenio Genovesi
- Institute of Cardiology, G. d'Annunzio University, Chieti, Italy
| | | | - Ugo Limbruno
- Cardiology Department, Azienda USL Toscana Sud-Est, Grosseto, Italy
| | | | | | | | - Giulia Renda
- Institute of Cardiology, G. d'Annunzio University, Chieti, Italy
| | - Marco Zimarino
- Institute of Cardiology, G. d'Annunzio University, Chieti, Italy
| | - Marta Di Nicola
- Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, Chieti, Italy
| | - Raffaele De Caterina
- University Cardiology Division, Pisa University Hospital, Pisa, Italy.,Fondazione Villa Serena per la Ricerca, Città Sant'Angelo, Pescara, Italy
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Xiao W, Lu Z, Liu Y, Hua T, Zhang J, Hu J, Li H, Xu Y, Yang M. Influence of the Initial Neutrophils to Lymphocytes and Platelets Ratio on the Incidence and Severity of Sepsis-Associated Acute Kidney Injury: A Double Robust Estimation Based on a Large Public Database. Front Immunol 2022; 13:925494. [PMID: 35903103 PMCID: PMC9320191 DOI: 10.3389/fimmu.2022.925494] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 06/16/2022] [Indexed: 11/17/2022] Open
Abstract
Background Acute kidney injury (AKI) is a frequent consequence of sepsis and has been linked to poor prognosis. In critically ill patients, the ratio of neutrophils to lymphocytes and platelets (N/LP) has been confirmed as an inflammation-related marker connected with the development of renal dysfunction. However, the effect of the N/LP ratio on the initiation and development of AKI in patients with sepsis remained unclear. The purpose of this study was to determine if the N/LP ratio on intensive care unit (ICU) admission was associated with the occurrence of sepsis-associated AKI (S-AKI) and severe AKI. Methods Adult septic patients from the Medical Information Mart for Intensive Care-IV database were screened and classified into three categories (low, middle, or high) based on their N/LP ratio quartiles. The Cox proportional hazard and competing risk models were used to determine the risk of S-AKI in various N/LP groups, whilst the logistic regression model and restricted cubic splines (RCS) analysis were employed to investigate the link between N/LP ratios and the occurrence of severe AKI. Finally, we did a doubly robust estimation, a subgroup analysis, and a sensitivity analysis to determine the findings’ robustness. Results We categorized 485, 968, and 485 septic patients into three groups based on their N/LP ratios: low, intermediate, and high. According the Cox proportional hazard model, the hazard rate (95% CI) for those in the middle and high N/LP groups on the incidence of S-AKI were 1.30(1.07, 1.58) and 1.27(1.02, 1.59), respectively, as compared to those in the low N/LP group. And the Fine-Gray proportional subdistribution hazards model indicated that mortality was not a substantial competing risk for S-AKI. Additionally, multivariate logistic regression revealed that the risk of severe AKI increased 1.83 fold in the high group compared to the low group. The RCS result also suggested that the probability of severe AKI rose significantly when N/LP > 9.5. The consistency of these findings was confirmed using doubly robust estimation. However, subgroup and sensitivity analyses revealed that the association between N/LP and the incidence of S-AKI, severe AKI varied considerably between different populations and diagnostic criteria. Conclusion A raised initial N/LP level may induce the development of S-AKI and severe AKI within 7 days after ICU admission in septic patients. These influences were enhanced in elder, male, septic shock, and those with poor health condition. Furthermore, high NLP was more strongly connected to the risk of S-AKI and severe AKI in sepsis patients on the urine output-based AKI criteria than on the serum creatinine-based criteria.
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Affiliation(s)
- Wenyan Xiao
- The 2nd Department of Intensive Care Unit, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zongqing Lu
- The 2nd Department of Intensive Care Unit, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yu Liu
- Key Laboratory of Intelligent Computing and Signal Processing, Anhui University, Ministry of Education, Hefei, China
- School of Integrated Circuits, Anhui University, Hefei, China
| | - Tianfeng Hua
- The 2nd Department of Intensive Care Unit, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jin Zhang
- The 2nd Department of Intensive Care Unit, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Juanjuan Hu
- The 2nd Department of Intensive Care Unit, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Hui Li
- The 2nd Department of Intensive Care Unit, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yaohua Xu
- Key Laboratory of Intelligent Computing and Signal Processing, Anhui University, Ministry of Education, Hefei, China
- School of Integrated Circuits, Anhui University, Hefei, China
| | - Min Yang
- The 2nd Department of Intensive Care Unit, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
- *Correspondence: Min Yang,
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The Most Promising Biomarkers of Allogeneic Kidney Transplant Rejection. J Immunol Res 2022; 2022:6572338. [PMID: 35669103 PMCID: PMC9167141 DOI: 10.1155/2022/6572338] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 04/30/2022] [Indexed: 12/13/2022] Open
Abstract
Clinical transplantology is a constantly evolving field of medicine. Kidney transplantation has become standard clinical practice, and it has a significant impact on reducing mortality and improving the quality of life of patients. Allogenic transplantation induces an immune response, which may lead to the rejection of the transplanted organ. The gold standard for evaluating rejection of the transplanted kidney by the recipient's organism is a biopsy of this organ. However, due to the high invasiveness of this procedure, alternative diagnostic methods are being sought. Therefore, the biomarkers may play an essential predictive role in transplant rejection. A review of the most promising biomarkers for early diagnosis and prognosis prediction of allogenic kidney transplant rejection summarizes novel data on neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), C-X-C motif chemokine 10 (CXCL-10), cystatin C (CysC), osteopontin (OPN), and clusterin (CLU) and analyses the dynamics of changes of the biomarkers mentioned above in kidney diseases and the mechanism of rejection of the transplanted kidney.
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Biomarkers of acute kidney injury after pediatric cardiac surgery: a meta-analysis of diagnostic test accuracy. Eur J Pediatr 2022; 181:1909-1921. [PMID: 35039910 DOI: 10.1007/s00431-022-04380-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 01/05/2022] [Accepted: 01/09/2022] [Indexed: 12/29/2022]
Abstract
UNLABELLED Acute kidney injury (AKI) occurs frequently after cardiac surgery in children. Although current diagnostic criteria rely on serum creatinine and urine output, changes occur only after considerable loss of kidney function. This meta-analysis aimed to synthesize the knowledge on novel biomarkers and compare their ability to predict AKI. PubMed/MEDLINE, Embase, Scopus, and reference lists were searched for relevant studies published by March 2021. Diagnostic accuracy parameters were extracted and analyzed using hierarchical summary receiver operating characteristic (HSROC) method. Pooled estimates of the area under the curve (AUC) were calculated using conventional random-effects meta-analysis. Fifty-six articles investigating 49 biomarkers in 8617 participants fulfilled our eligibility criteria. Data from 37 studies were available for meta-analysis. Of the 10 biomarkers suitable for HSROC analysis, urinary neutrophil gelatinase-associated lipocalin (uNGAL) to creatinine (Cr) ratio yielded the highest diagnostic odds ratio (91.0, 95% CI 90.1-91.9), with a sensitivity of 91.3% (95% CI 91.2-91.3%) and a specificity of 89.7% (95% CI 89.6-89.7%). These results were confirmed in pooled AUC analysis, as uNGAL-to-Cr ratio and uNGAL were the only elaborately studied biomarkers (> 5 observations) with pooled AUCs ≥ 0.800. Liver fatty acid-binding protein (L-FABP), serum cystatin C (sCysC), serum NGAL (sNGAL), and interleukin-18 (IL-18) all had AUCs ≥ 0.700. CONCLUSION A variety of biomarkers have been proposed as predictors of cardiac surgery-associated AKI in children, of which uNGAL was the most prominent with excellent diagnostic qualities. However, more consolidatory evidence will be required before these novel biomarkers may eventually help realize precision medicine in AKI management. WHAT IS KNOWN • Acute kidney injury (AKI) occurs in about 30-60% of children undergoing cardiac surgery and is associated with increased in-hospital mortality and adverse short-term outcomes. However, in current clinical practice, AKI definitions and detection often rely on changes in serum creatinine and urine output, which are late and insensitive markers of kidney injury. • Although various novel biomarkers have been studied for the diagnosis of AKI in children after cardiac surgery, it remains unclear how these compare to one another in terms of diagnostic accuracy. WHAT IS NEW • Pooled analyses suggest that for the diagnosis of AKI in children who underwent cardiac surgery, NGAL is the most accurate among the most frequently studied biomarkers. • A number of other promising biomarkers have been reported, although they will require further research into their diagnostic accuracy and clinical applicability.
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Alshehri AM, Alzahrani MY, Abujamal MA, Abdalla MH, Alowais SA, Alfayez OM, Alyami MS, Almutairi AR, Almohammed OA. Comparative Risk of Acute Kidney Injury Following Concurrent Administration of Vancomycin with Piperacillin/Tazobactam or Meropenem: A Systematic Review and Meta-Analysis of Observational Studies. Antibiotics (Basel) 2022; 11:antibiotics11040526. [PMID: 35453276 PMCID: PMC9031739 DOI: 10.3390/antibiotics11040526] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 04/11/2022] [Accepted: 04/12/2022] [Indexed: 01/27/2023] Open
Abstract
The study aims to comparatively assess the nephrotoxicity of vancomycin when combined with piperacillin-tazobactam (V + PT) or meropenem (V + M) in adult patients hospitalized in general wards or intensive care units. We searched MEDLINE, Google Scholar, and Web of Science for observational studies evaluating incidences of AKI in adult patients receiving V + PT or V + M for at least 48 h in general wards or intensive care units. The primary outcome was AKI events, while the secondary outcomes were hospital length of stay, need for renal replacement therapy (RRT), and mortality events. The odds ratio (OR), or mean difference for the hospital length of stay, with a corresponding 95% confidence interval (CI) from the inverse variance weighting random-effects model were estimated for the risk of AKI, RRT, and mortality. Of the 112 studies identified, twelve observational studies were included in this meta-analysis with a total of 14,511 patients. The odds of having AKI were significantly higher in patients receiving V + PT compared with V + M (OR = 2.31; 95%CI 1.69–3.15). There were no differences between V + PT and V + M in the hospital length of stay, RRT, or mortality outcomes. Thus, clinicians should be vigilant while using V + PT, especially in patients who are at high risk of AKI.
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Affiliation(s)
- Abdulmajeed M. Alshehri
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh 14611, Saudi Arabia; (A.M.A.); (M.Y.A.); (M.A.A.); (M.H.A.); (S.A.A.); (M.S.A.)
| | - Mohammed Y. Alzahrani
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh 14611, Saudi Arabia; (A.M.A.); (M.Y.A.); (M.A.A.); (M.H.A.); (S.A.A.); (M.S.A.)
| | - Mohammed A. Abujamal
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh 14611, Saudi Arabia; (A.M.A.); (M.Y.A.); (M.A.A.); (M.H.A.); (S.A.A.); (M.S.A.)
| | - Mariam H. Abdalla
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh 14611, Saudi Arabia; (A.M.A.); (M.Y.A.); (M.A.A.); (M.H.A.); (S.A.A.); (M.S.A.)
| | - Shuroug A. Alowais
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh 14611, Saudi Arabia; (A.M.A.); (M.Y.A.); (M.A.A.); (M.H.A.); (S.A.A.); (M.S.A.)
- King Abdulaziz Medical City, National Guard Health Affairs, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia
| | - Osamah M. Alfayez
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia;
| | - Majed S. Alyami
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh 14611, Saudi Arabia; (A.M.A.); (M.Y.A.); (M.A.A.); (M.H.A.); (S.A.A.); (M.S.A.)
- King Abdulaziz Medical City, National Guard Health Affairs, Riyadh 11426, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia
| | | | - Omar A. Almohammed
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia
- Pharmacoeconomics Research Unit, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia
- Correspondence: ; Tel.: +966-555104065
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Batte A, Menon S, Ssenkusu J, Kiguli S, Kalyesubula R, Lubega J, Mutebi EI, Opoka RO, John CC, Starr MC, Conroy AL. Acute kidney injury in hospitalized children with sickle cell anemia. BMC Nephrol 2022; 23:110. [PMID: 35303803 PMCID: PMC8933904 DOI: 10.1186/s12882-022-02731-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 03/08/2022] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Children with sickle cell anemia (SCA) are at increased risk of acute kidney injury (AKI) that may lead to death or chronic kidney disease. This study evaluated AKI prevalence and risk factors in children with SCA hospitalized with a vaso-occlusive crisis (VOC) in a low-resource setting. Further, we evaluated whether modifications to the Kidney Disease: Improving Global Outcomes (KDIGO) definition would influence clinical outcomes of AKI in children with SCA hospitalized with a VOC. METHODS We prospectively enrolled 185 children from 2 - 18 years of age with SCA (Hemoglobin SS) hospitalized with a VOC at a tertiary hospital in Uganda. Kidney function was assessed on admission, 24-48 h of hospitalization, and day 7 or discharge. Creatinine was measured enzymatically using an isotype-dilution mass spectrometry traceable method. AKI was defined using the original-KDIGO definition as ≥ 1.5-fold change in creatinine within seven days or an absolute change of ≥ 0.3 mg/dl within 48 h. The SCA modified-KDIGO (sKDIGO) definition excluded children with a 1.5-fold change in creatinine from 0.2 mg/dL to 0.3 mg/dL. RESULTS Using KDIGO, 90/185 (48.7%) children had AKI with 61/185 (33.0%) AKI cases present on admission, and 29/124 (23.4%) cases of incident AKI. Overall, 23 children with AKI had a 1.5-fold increase in creatinine from 0.2 mg/dL to 0.3 m/dL. Using the sKDIGO-definition, 67/185 (36.2%) children had AKI with 43/185 (23.2%) cases on admission, and 24/142 (16.9%) cases of incident AKI. The sKDIGO definition, but not the original-KDIGO definition, was associated with increased mortality (0.9% vs. 7.5%, p = 0.024). Using logistic regression, AKI risk factors included age (aOR, 1.10, 95% CI 1.10, 1.20), hypovolemia (aOR, 2.98, 95% CI 1.08, 8.23), tender hepatomegaly (aOR, 2.46, 95% CI 1.05, 5.81), and infection (aOR, 2.63, 95% CI 1.19, 5.81) (p < 0.05). CONCLUSION These results demonstrate that AKI is a common complication in children with SCA admitted with VOC. The sKDIGO definition of AKI in children with SCA was a better predictor of clinical outcomes in children. There is need for promotion of targeted interventions to ensure early identification and treatment of AKI in children with SCA.
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Affiliation(s)
- Anthony Batte
- Child Health and Development Centre, Makerere University College of Health Sciences, P.O Box 6717, Kampala, Uganda.
| | - Sahit Menon
- San Diego School of Medicine, University of California, San Diego, USA
| | - John Ssenkusu
- Department of Epidemiology and Biostatistics, Makerere University School of Public Health, Kampala, Uganda
| | - Sarah Kiguli
- Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
| | | | - Joseph Lubega
- Pediatric Hematology and Oncology, Baylor College of Medicine, Texas, USA
| | | | - Robert O Opoka
- Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
| | - Chandy C John
- Department of Pediatrics, Ryan White Center for Pediatric Infectious Disease and Global Health, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Michelle C Starr
- Department of Pediatrics, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Andrea L Conroy
- Department of Pediatrics, Ryan White Center for Pediatric Infectious Disease and Global Health, Indiana University School of Medicine, Indianapolis, IN, USA
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Zahler D, Lee-Rozenfeld K, Itach T, Lupu L, Banai S, Shacham Y. Time is Kidney: Relation between Pain to Balloon Time and Acute Kidney Injury among ST Segment Elevation Patients Undergoing Primary Percutaneous intervention. Cardiorenal Med 2022; 12:55-60. [DOI: 10.1159/000523829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 02/10/2022] [Indexed: 11/19/2022] Open
Abstract
Background: Among ST segment elevation myocardial infarction (STEMI) early hemodynamic changes may result in acute kidney injury (AKI) even prior to primary percutaneous coronary intervention (PCI), however, no information to date is present regarding the association between pain to balloon (PBT) and AKI. We evaluated whether PBT predicts the risk of AKI among STEMI patients undergoing primary PCI.
Methods: Medical records of 2343 STEMI patients undergoing primary PCI were reviewed. Patients were stratified by PBT into 3 groups: ≤120, 121-360 and > 360 minutes. Patients' records were assessed for the occurrence of AKI (defined by the KDIGO criteria as serum creatinine elevation ≥ 0.3 mg/dl within 72 hours after admission).
Results: Mean age was 61 ± 13 years and 1919 (82%) were male. Patients having longer PBT had more AKI complicating the course of STEMI (7 % vs. 8 % vs. 13 %, p<0.001) and had significantly higher serum creatinine changes throughout hospitalization (0.08 mg/dl vs. 0.11 mg/dl vs.0.17 mg/dl p<0.001). In a multivariable logistic regression model each 1-hour increase in PBT was independently associated with a 2.2% increase in risk for AKI (OR 1.022, 95% CI 1.01-1.04, p=0.02).
Conclusion: Longer PBT may be an independent marker for the development of AKI in STEMI patients undergoing primary.
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Van den Eynde J, Delpire B, Jacquemyn X, Pardi I, Rotbi H, Gewillig M, Kutty S, Mekahli D. Risk factors for acute kidney injury after pediatric cardiac surgery: a meta-analysis. Pediatr Nephrol 2022; 37:509-519. [PMID: 34595570 DOI: 10.1007/s00467-021-05297-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 09/16/2021] [Accepted: 09/16/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND Cardiac surgery-associated acute kidney injury (AKI) is associated with increased morbidity and mortality in both adults and children. OBJECTIVES This study aimed to identify clinical risk factors for AKI following cardiac surgery in the pediatric population. DATA SOURCES PubMed/MEDLINE, Embase, Scopus, and reference lists of relevant articles were searched for studies published by August 2020. STUDY ELIGIBILITY CRITERIA Studies were included if (1) the population consisted of pediatric patients (< 18 years old), (2) patients underwent cardiac surgery, (3) risk factors were compared between patients who developed AKI and those who did not, and (4) studies were prospective or retrospective observational studies or randomized controlled trials. PARTICIPANTS AND INTERVENTIONS Children undergoing pediatric cardiac surgery. STUDY APPRAISAL AND SYNTHESIS METHODS Random-effects meta-analysis was performed, comparing potential risk factors between pediatric patients who developed CS-AKI and those who did not. RESULTS Sixty-one publications including a total of 19,680 participants (AKI: 7257 participants; no AKI: 12,423 participants) were included from studies published between 2008 and 2020. The pooled estimated incidence of AKI was 34.3% (95% confidence interval 30.0-38.8%, I2 = 96.8%). Binary risk factors that were significantly and consistently associated with AKI were the presence of pulmonary hypertension, cyanotic heart disease, univentricular heart, risk adjustment for congenital heart surgery 1 (RACHS-1) score ≥ 3, vasopressor use, cardiopulmonary bypass use, reoperation, and sepsis. Significant continuous risk factors included younger age, lower body weight, lower preoperative creatinine, higher preoperative estimated glomerular filtration rate (eGFR), higher RACHS-1 score, longer surgery time, longer cardiopulmonary bypass time, longer aortic cross-clamp time, and higher red blood cell transfusion volume. LIMITATIONS Results are limited by heterogeneity and potential residual confounding. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS Our meta-analysis identified clinical risk factors that are associated with AKI in children undergoing cardiac surgery. This might help clinicians anticipate and manage more carefully this population and implement standardized preventive strategies. SYSTEMATIC REVIEW REGISTRATION NUMBER CRD42021262699. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Jef Van den Eynde
- Helen B. Taussig Heart Center, The Johns Hopkins Hospital and School of Medicine, Baltimore, USA. .,Department of Cardiovascular Sciences, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
| | - Boris Delpire
- Department of Cardiovascular Sciences, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
| | - Xander Jacquemyn
- Department of Cardiovascular Sciences, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
| | - Ismat Pardi
- Department of Cardiovascular Sciences, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
| | - Hajar Rotbi
- Faculty of Medicine, Radboud University, Nijmegen, The Netherlands.,Department of Physiology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands
| | - Marc Gewillig
- Department of Cardiovascular Sciences, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.,Pediatric Cardiology, University Hospitals Leuven, Leuven, Belgium
| | - Shelby Kutty
- Helen B. Taussig Heart Center, The Johns Hopkins Hospital and School of Medicine, Baltimore, USA
| | - Djalila Mekahli
- Department of Pediatric Nephrology, University Hospitals of Leuven, Leuven, Belgium.,PKD Research Group, GPURE, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
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Acute Kidney Injury: Biomarker-Guided Diagnosis and Management. Medicina (B Aires) 2022; 58:medicina58030340. [PMID: 35334515 PMCID: PMC8953384 DOI: 10.3390/medicina58030340] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/21/2022] [Accepted: 02/22/2022] [Indexed: 12/23/2022] Open
Abstract
Acute kidney injury (AKI) is a common clinical syndrome that is characterized by abnormal renal function and structure. The Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference in 2019 reviewed the stages of AKI and the definitions of AKI-related terminologies, and discussed the advances in the last decade. Along with serum creatinine level and urine output, more accurate novel biomarkers for predicting AKI are being applied for the early detection of renal dysfunction. A literature search was conducted in PubMed, Scopus, Medline, and ClinicalTrials.gov using the terms AKI and biomarker, combined with diagnosis, management, or prognosis. Because of the large volume of data (160 articles) published between 2005 and 2022, representative literature was chosen. A number of studies have demonstrated that new biomarkers are more sensitive in detecting AKI in certain populations than serum creatinine and urine output according to the recommendations from the Acute Disease Quality Initiative Consensus Conference. To be specific, there is a persistently unresolved need for earlier detection of patients with AKI before AKI progresses to a need for renal replacement therapy. Biomarker-guided management may help to identify a high-risk group of patients in progression to severe AKI, and decide the initiation time to renal replacement therapy and optimal follow-up period. However, limitations such as biased data to certain studied populations and absence of cutoff values need to be solved for worldwide clinical use of biomarkers in the future. Here, we provide a comprehensive review of biomarker-based AKI diagnosis and management and highlight recent developments.
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Impact of retrograde intrarenal surgery on biomarkers that are associated with renal parenchyma injury, a preliminary study. World J Urol 2022; 40:841-847. [PMID: 35066638 DOI: 10.1007/s00345-021-03909-w] [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: 10/04/2021] [Accepted: 12/07/2021] [Indexed: 10/19/2022] Open
Abstract
PURPOSE The primary objective of this preliminary study was to assess the changes in concentration of biomarkers, which indicate renal injury, after RIRS. MATERIALS AND METHODS Within this prospective study, we included 21 patients with nephrolithiasis requiring treatment with RIRS. From each patient, blood and urine samples were taken at fixed intervals before and after RIRS. Kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), calbindin, albumin, clusterin, gluthation S-transferase-π (GST-π), beta-2-microglobulin (B2M), osteopontin, cystatin c, and trefoil-factor-3 (TFF3) were measured in urine. Creatinine, cystatin c and uric acid were analyzed in the blood samples. RESULTS A significant increase of the biomarkers clusterin, GST-π, B2M, NGAL and cystatin c was observed after RIRS. However, the biomarkers gradually normalized during the first 14 postoperative days. The parameters surgery time, cumulative stone volume, and BMI did not significantly influence the biomarker concentrations. In the case of GST-π and NGAL a significant positive, yet minuscule effect of age was observed. CONCLUSIONS With our study, we identified 5 out of 12 assessed renal injury biomarkers that showed a significant increase after RIRS. The increase was only temporary and all markers normalized within 14 days. Further studies are needed to determine the clinical value of these identified markers to assess the long-term impact of intrarenal pressure elevation during RIRS.
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Protective role of antithrombin III in suppressing acute responses in a rat model of renal ischemia-reperfusion injury. Mol Cell Biochem 2022; 477:627-634. [PMID: 34984594 DOI: 10.1007/s11010-021-04322-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 11/29/2021] [Indexed: 12/13/2022]
Abstract
Renal ischemia-reperfusion (IR) produces-induced injury and is characterized by restriction of blood supply to the kidney followed by restoration and re-oxygenation of the tissue. IR injury in the kidney contributes to pathological processes known as acute renal injury (ARI). Ischemia-perfusion injury (IRI) of the left renal artery has been demonstrated in Wistar rats. A total of 32 animals were divided into four groups: control group (SHAM), IR animals with induced ischemia-reperfusion, AT-IR animals treated by antithrombin III (AT) before IR, and AT-IR-AT animals with AT administered before and after IR. IR-induced hyperproteinemia, hyperalbuminemia, hyperglobulinemia, and a significantly low A/G ratio. Exogenous administration of AT prior to IR development effectively regulates protein fraction levels by establishing normoproteinemia. The preventive effect of AT regulates serum protein levels and reduces acute inflammation by reducing globulin and establishing physiological levels of A/G ratios. The therapeutic effect of AT given after IR is not effective compared to AT administered before IR. Protein fractions can serve as an important predictive marker for the prognosis and duration of acute inflammation. Serum globulin levels and the A/G ratio may serve as effective prognostic markers in acute inflammation caused by ischemia-reperfusion injury of the kidney. A strong correlation between globulin and the A/G ratio suggests novel markers associated with acute inflammation that can lead to chronic kidney disease.
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Fu K, Hu Y, Zhang H, Wang C, Lin Z, Lu H, Ji X. Insights of Worsening Renal Function in Type 1 Cardiorenal Syndrome: From the Pathogenesis, Biomarkers to Treatment. Front Cardiovasc Med 2022; 8:760152. [PMID: 34970606 PMCID: PMC8712491 DOI: 10.3389/fcvm.2021.760152] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 11/11/2021] [Indexed: 12/16/2022] Open
Abstract
Type-1 cardiorenal syndrome refers to acute kidney injury induced by acute worsening cardiac function. Worsening renal function is a strong and independent predictive factor for poor prognosis. Currently, several problems of the type-1 cardiorenal syndrome have not been fully elucidated. The pathogenesis mechanism of renal dysfunction is unclear. Besides, the diagnostic efficiency, sensitivity, and specificity of the existing biomarkers are doubtful. Furthermore, the renal safety of the therapeutic strategies for acute heart failure (AHF) is still ambiguous. Based on these issues, we systematically summarized and depicted the research actualities and predicaments of the pathogenesis, diagnostic markers, and therapeutic strategies of worsening renal function in type-1 cardiorenal syndrome.
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Affiliation(s)
- Kang Fu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Yue Hu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Hui Zhang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Chen Wang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Zongwei Lin
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Huixia Lu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Xiaoping Ji
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
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Yousefifard M, Ahmadzadeh K, Toloui A, Ahmadzadeh H, Madani Neishaboori A, Rafiei Alavi SN, Ghelichkhani P, Tavallaei MJ, Safari S, Ataei N, Hosseini M. Assessing the value of serum and urinary interleukins for diagnosis of acute kidney injury in children and adolescents: A systematic review and meta-analysis. Pract Lab Med 2022; 28:e00262. [PMID: 35071719 PMCID: PMC8762046 DOI: 10.1016/j.plabm.2022.e00262] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 12/18/2021] [Accepted: 01/03/2022] [Indexed: 02/06/2023] Open
Abstract
Introduction Method Results Conclusion
Urinary level of IL-18 is significantly higher in AKI children in comparison with non-AKI children. Serum levels of IL-6 and IL-8 are significantly higher in AKI children in comparison with non-AKI children. Overall, the sensitivity and specificity of these markers are not desirable for diagnosing AKI. Future studies should be directed towards unifying cut-off points for these markers.
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Yu H, Kim H, Shin HS, Lee HS. Prediction of renal function improvement in azotemic patients using glomerular filtration rate from 99mTc-DTPA renal scan: An observational study. Medicine (Baltimore) 2021; 100:e28332. [PMID: 34941135 PMCID: PMC8702227 DOI: 10.1097/md.0000000000028332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 11/30/2021] [Indexed: 01/05/2023] Open
Abstract
This study aimed to evaluate the ratio of glomerular filtration rate (GFR) from 99mTc-diethylenetriamine-pentaacetic acid dynamic renal scan (GFRSCAN) to estimated GFR (eGFR) as a predictor of renal function improvement in patients with azotemia.A retrospective review of medical records was conducted to identify consecutive patients with newly discovered or aggravated azotemia who underwent 99mTc-diethylenetriamine-pentaacetic acid renal scan. Significant renal function improvement was defined as ≥100% and ≥10 mL/min improvement of eGFR at 12 weeks compared to eGFR on the day of renal scan (eGFR0). The GFRSCAN/eGFR0 ratio was evaluated as a predictor of significant renal function improvement using logistic regression and receiver operating characteristic (ROC) curve analyses. Added value of the GFRSCAN/eGFR0 ratio in the prediction of significant renal function improvement were demonstrated by adjusting for best clinical predictor variables.The eligibility criteria were met by 224 patients, among whom 22 patients (9.8%) showed significant renal function improvement. The odds ratios of the GFRSCAN/eGFR0 ratio for predicting significant renal function improvement were 1.76 (95% confidence interval [CI]: 1.26-2.45, P < .001) in the univariable analysis and 1.70 (95% CI: 1.19-2.42, P = .003) after adjusting for clinical variables. The area under the ROC curve of the GFRSCAN/eGFR0 ratio for predicting significant renal function improvement was 0.762 (95% CI: 0.648-0.871). The addition of the GFRSCAN/eGFR0 ratio to the best clinical prediction model raised the area under the ROC curve from 0.726 to 0.794, and this increment was statistically significant (P = .02).The GFRSCAN/eGFR ratio can predict renal function improvement in patients with azotemia. Future prospective studies are necessary to validate its potential clinical utilities.
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Affiliation(s)
- Hoon Yu
- Division of Nephrology, Department of Internal Medicine, GangNeung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea
| | - Hyosang Kim
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyung Soo Shin
- Department of Chemistry, College of Letters & Science, University of California, Davis, United States of America
| | - Hyo Sang Lee
- Department of Nuclear Medicine, GangNeung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea
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Gambaro A, Lombardi G, Onorati F, Gottin L, Ribichini FL. Heart, kidney and left ventricular assist device: a complex trio. Eur J Clin Invest 2021; 51:e13662. [PMID: 34347897 DOI: 10.1111/eci.13662] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/24/2021] [Accepted: 08/03/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND Heart failure (HF) is a complex syndrome affecting the whole body, kidneys included. The left ventricular assist device (LVAD) is a valid option for patients with very severe HF. Focusing on renal function, LVAD implantation could theoretically reverse the detrimental effects of HF syndrome on kidneys. However, implanting an LVAD is a high-risk surgical procedure, and LVAD patients have higher risk of bleeding, device thrombosis, strokes, renal impairment, multi-organ failure and infections. Furthermore, an LVAD has its own particular effects on the renal system. METHODS In this review, we provide a comprehensive overview of the complex interaction between LVAD and the kidneys from the pathophysiological and clinical perspectives. An analysis of the different effects of pulsatile-flow and continuous-flow LVAD is provided. RESULTS Despite their limitations, creatinine-based estimated glomerular filtration rate (eGFR) formulas help to stratify patients by their post-LVAD placement prognosis. Poor basal renal function, the onset of acute kidney injury or the need for renal replacement therapy after LVAD implantation negatively influences a patient's prognosis. LVAD can also prompt an improvement in renal function, however, with some counterintuitive effects on a patient's prognosis. CONCLUSION It is still hard to say whether different trends in eGFR depend on different renal conditions before LVAD placement, on a patient's better overall status or on a particular patient management strategy before and/or after the device's implantation. Steps should be taken to solve this question because finding the best candidates for LVAD implantation is of paramount importance to ensure the best outcomes.
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Affiliation(s)
- Alessia Gambaro
- Division of Cardiology, Department of Medicine, University of Verona, Verona, Italy
| | - Gianmarco Lombardi
- Division of Nephrology, Department of Medicine, University of Verona, Verona, Italy
| | | | - Leonardo Gottin
- Unit of Cardiothoracic Anesthesia and Intensive Care, Department of Emergencies and Intensive Care, University of Verona, Verona, Italy
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Elsayed MS, Abu-Elsaad NM, Nader MA. The NLRP3 inhibitor dapansutrile attenuates folic acid induced nephrotoxicity via inhibiting inflammasome/caspase-1/IL axis and regulating autophagy/proliferation. Life Sci 2021; 285:119974. [PMID: 34560082 DOI: 10.1016/j.lfs.2021.119974] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 09/15/2021] [Accepted: 09/17/2021] [Indexed: 11/26/2022]
Abstract
AIMS Chemical renal toxicity is common and has limited therapeutic interventions. The NLRP3 inhibitor dapansutrile (DAPA) undergoes clinical phase II trials and it shows promising beneficial effects in various inflammatory diseases. The current study aims at evaluating the effect of DAPA on folic acid (FA) induced acute kidney injury (AKI) and its possible transition to chronic injury. MATERIALS AND METHODS Two treatment protocols were studied depending on DAPA injection timing. A prophylactic protocol involving the injection of DAPA (0.2 mg/kg) daily for seven days before FA challenge and a therapeutic protocol where DAPA was injected after FA. Each protocol included four groups of rats: control group, DAPA group, FA group and DAPA+FA group. Serum creatinine, urea and uric acid were measured. Also, kidney injury, necrosis and fibrosis percentage in addition to infiltration of CD68 positive cells were evaluated. Activation markers of inflammasome and the expression of Ki-67 and LC-3 were measured. KEY FINDINGS Results showed an improvement in renal tissue integrity and a significant decrease in kidney function biomarkers, caspase-1, IL-1β and IL-18 by DAPA injection (p < 0.05). In addition, DAPA decreased the proliferation marker Ki-67 and the autophagic marker LC-3 (p < 0.01). SIGNIFICANCE DAPA potentially alleviates FA induced nephrotoxicity through targeting inflammasome/caspase-1/IL axis. Moreover, it shows a regulatory effect on renal regeneration and autophagy.
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Affiliation(s)
- Mohamed S Elsayed
- Pharmacology and Toxicology Dep., Faculty of Pharmacy, Mansoura University, Egypt
| | - Nashwa M Abu-Elsaad
- Pharmacology and Toxicology Dep., Faculty of Pharmacy, Mansoura University, Egypt.
| | - Manar A Nader
- Pharmacology and Toxicology Dep., Faculty of Pharmacy, Mansoura University, Egypt
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Kapetanaki S, Kumawat AK, Persson K, Demirel I. The Fibrotic Effects of TMAO on Human Renal Fibroblasts Is Mediated by NLRP3, Caspase-1 and the PERK/Akt/mTOR Pathway. Int J Mol Sci 2021; 22:ijms222111864. [PMID: 34769294 PMCID: PMC8584593 DOI: 10.3390/ijms222111864] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 10/24/2021] [Accepted: 10/30/2021] [Indexed: 02/06/2023] Open
Abstract
Trimethylamine N-oxide (TMAO), a product of gut microbiota metabolism, has previously been shown to be implicated in chronic kidney disease. A high TMAO-containing diet has been found to cause tubulointerstitial renal fibrosis in mice. However, today there are no data linking specific molecular pathways with the effect of TMAO on human renal fibrosis. The aim of this study was to investigate the fibrotic effects of TMAO on renal fibroblasts and to elucidate the molecular pathways involved. We found that TMAO promoted renal fibroblast activation and fibroblast proliferation via the PERK/Akt/mTOR pathway, NLRP3, and caspase-1 signaling. We also found that TMAO increased the total collagen production from renal fibroblasts via the PERK/Akt/mTOR pathway. However, TMAO did not induce fibronectin or TGF-β1 release from renal fibroblasts. We have unraveled that the PERK/Akt/mTOR pathway, NLRP3, and caspase-1 mediates TMAO’s fibrotic effect on human renal fibroblasts. Our results can pave the way for future research to further clarify the molecular mechanism behind TMAO’s effects and to identify novel therapeutic targets in the context of chronic kidney disease.
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Affiliation(s)
- Stefania Kapetanaki
- School of Medical Sciences, Campus USÖ, Örebro University, 701 82 Örebro, Sweden; (A.K.K.); (K.P.); (I.D.)
- Nephrology Department, Karolinska University Hospital, 171 76 Solna, Sweden
- Nephrology Department, Karolinska University Hospital, 141 86 Huddinge, Sweden
- Correspondence: ; Tel.: +46-1930-3000
| | - Ashok Kumar Kumawat
- School of Medical Sciences, Campus USÖ, Örebro University, 701 82 Örebro, Sweden; (A.K.K.); (K.P.); (I.D.)
- Cardiovascular Research Center, School of Medical Sciences, Örebro University, 701 82 Örebro, Sweden
| | - Katarina Persson
- School of Medical Sciences, Campus USÖ, Örebro University, 701 82 Örebro, Sweden; (A.K.K.); (K.P.); (I.D.)
- iRiSC—Inflammatory Response and Infection Susceptibility Center, Faculty of Medicine and Health, Örebro University, 701 82 Örebro, Sweden
| | - Isak Demirel
- School of Medical Sciences, Campus USÖ, Örebro University, 701 82 Örebro, Sweden; (A.K.K.); (K.P.); (I.D.)
- iRiSC—Inflammatory Response and Infection Susceptibility Center, Faculty of Medicine and Health, Örebro University, 701 82 Örebro, Sweden
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Saito R, Hirayama A, Akiba A, Kamei Y, Kato Y, Ikeda S, Kwan B, Pu M, Natarajan L, Shinjo H, Akiyama S, Tomita M, Soga T, Maruyama S. Urinary Metabolome Analyses of Patients with Acute Kidney Injury Using Capillary Electrophoresis-Mass Spectrometry. Metabolites 2021; 11:671. [PMID: 34677386 PMCID: PMC8540909 DOI: 10.3390/metabo11100671] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 09/28/2021] [Accepted: 09/28/2021] [Indexed: 12/29/2022] Open
Abstract
Acute kidney injury (AKI) is defined as a rapid decline in kidney function. The associated syndromes may lead to increased morbidity and mortality, but its early detection remains difficult. Using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS), we analyzed the urinary metabolomic profile of patients admitted to the intensive care unit (ICU) after invasive surgery. Urine samples were collected at six time points: before surgery, at ICU admission and 6, 12, 24 and 48 h after. First, urine samples from 61 initial patients (non-AKI: 23, mild AKI: 24, severe AKI: 14) were measured, followed by the measurement of urine samples from 60 additional patients (non-AKI: 40, mild AKI: 20). Glycine and ethanolamine were decreased in patients with AKI compared with non-AKI patients at 6-24 h in the two groups. The linear statistical model constructed at each time point by machine learning achieved the best performance at 24 h (median AUC, area under the curve: 89%, cross-validated) for the 1st group. When cross-validated between the two groups, the AUC showed the best value of 70% at 12 h. These results identified metabolites and time points that show patterns specific to subjects who develop AKI, paving the way for the development of better biomarkers.
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Affiliation(s)
- Rintaro Saito
- Institute for Advanced Biosciences, Keio University, Tsuruoka 997-0052, Japan; (A.H.); (A.A.); (Y.K.); (Y.K.); (S.I.); (M.T.); (T.S.)
| | - Akiyoshi Hirayama
- Institute for Advanced Biosciences, Keio University, Tsuruoka 997-0052, Japan; (A.H.); (A.A.); (Y.K.); (Y.K.); (S.I.); (M.T.); (T.S.)
| | - Arisa Akiba
- Institute for Advanced Biosciences, Keio University, Tsuruoka 997-0052, Japan; (A.H.); (A.A.); (Y.K.); (Y.K.); (S.I.); (M.T.); (T.S.)
| | - Yushi Kamei
- Institute for Advanced Biosciences, Keio University, Tsuruoka 997-0052, Japan; (A.H.); (A.A.); (Y.K.); (Y.K.); (S.I.); (M.T.); (T.S.)
| | - Yuyu Kato
- Institute for Advanced Biosciences, Keio University, Tsuruoka 997-0052, Japan; (A.H.); (A.A.); (Y.K.); (Y.K.); (S.I.); (M.T.); (T.S.)
| | - Satsuki Ikeda
- Institute for Advanced Biosciences, Keio University, Tsuruoka 997-0052, Japan; (A.H.); (A.A.); (Y.K.); (Y.K.); (S.I.); (M.T.); (T.S.)
| | - Brian Kwan
- Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA 92093, USA; (B.K.); (M.P.); (L.N.)
| | - Minya Pu
- Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA 92093, USA; (B.K.); (M.P.); (L.N.)
| | - Loki Natarajan
- Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA 92093, USA; (B.K.); (M.P.); (L.N.)
| | - Hibiki Shinjo
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; (H.S.); (S.A.); (S.M.)
| | - Shin’ichi Akiyama
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; (H.S.); (S.A.); (S.M.)
| | - Masaru Tomita
- Institute for Advanced Biosciences, Keio University, Tsuruoka 997-0052, Japan; (A.H.); (A.A.); (Y.K.); (Y.K.); (S.I.); (M.T.); (T.S.)
| | - Tomoyoshi Soga
- Institute for Advanced Biosciences, Keio University, Tsuruoka 997-0052, Japan; (A.H.); (A.A.); (Y.K.); (Y.K.); (S.I.); (M.T.); (T.S.)
| | - Shoichi Maruyama
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; (H.S.); (S.A.); (S.M.)
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