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Lee PH, Huang SM, Tsai YC, Wang YT, Chew FY. Biomarkers in Contrast-Induced Nephropathy: Advances in Early Detection, Risk Assessment, and Prevention Strategies. Int J Mol Sci 2025; 26:2869. [PMID: 40243457 PMCID: PMC11989060 DOI: 10.3390/ijms26072869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 03/17/2025] [Accepted: 03/18/2025] [Indexed: 04/18/2025] Open
Abstract
Contrast-induced nephropathy (CIN) represents a significant complication associated with the use of iodinated contrast media (ICM), especially in individuals with preexisting renal impairment. The pathophysiology of CIN encompasses oxidative stress, inflammation, endothelial dysfunction, and hemodynamic disturbances, resulting in acute kidney injury (AKI). Early detection is essential for effective management; however, conventional markers like serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) exhibit limitations in sensitivity and timeliness. This review emphasizes the increasing significance of novel biomarkers in enhancing early detection and risk stratification of contrast-induced nephropathy (CIN). Recent advancements in artificial intelligence and computational analytics have improved the predictive capabilities of these biomarkers, enabling personalized risk assessment and precision medicine strategies. Additionally, we discuss mitigation strategies, including hydration protocols, pharmacological interventions, and procedural modifications, aimed at reducing CIN incidence. Incorporating biomarker-driven assessments into clinical decision-making can enhance patient management and outcomes. Future research must prioritize the standardization of biomarker assays, the validation of predictive models across diverse patient populations, and the exploration of novel therapeutic targets. Utilizing advancements in biomarkers and risk mitigation strategies allows clinicians to improve the safety of contrast-enhanced imaging and reduce the likelihood of renal injury.
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Affiliation(s)
- Pei-Hua Lee
- Department of Medical Imaging, China Medical University Hospital, Taichung 404, Taiwan
- Department of Radiology, School of Medicine, China Medical University, Taichung 404, Taiwan
| | - Shao Min Huang
- Department of Medical Education, Show Chwan Memorial Hospital, Changhua 500, Taiwan
| | - Yi-Ching Tsai
- Division of Endocrinology, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan
| | - Yu-Ting Wang
- Department of Pathology, Chung Shan Medical University Hospital, Taichung 402, Taiwan
- Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Fatt Yang Chew
- Department of Medical Imaging, China Medical University Hospital, Taichung 404, Taiwan
- Department of Radiology, School of Medicine, China Medical University, Taichung 404, Taiwan
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Mattke AC, Johnson KE, Ariyawansa K, Trnka P, Venugopal PS, Coman D, Schibler A, Gibbons K. Urinary chloride excretion in critical illness and acute kidney injury: a paediatric hypothesis-generating cohort study post cardiopulmonary bypass surgery. Anaesth Intensive Care 2024; 52:397-406. [PMID: 39257339 DOI: 10.1177/0310057x241265119] [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: 09/12/2024]
Abstract
Renal chloride metabolism is currently poorly understood but may serve as both a diagnostic and a treatment approach for acute kidney injury. We investigated whether plasma chloride, ammonia and glutamine as well as urinary chloride, ammonium and glutamine concentrations may serve as markers for acute kidney injury in paediatric patients. We conducted a prospective observational trial in a tertiary care paediatric intensive care unit. Ninety-one patients after cardiopulmonary bypass surgery were enrolled. Plasma glutamine, creatinine, (serum) albumin, urinary electrolytes and glutamine were collected pre-cardiopulmonary bypass surgery, at paediatric intensive care unit admission, and at 6, 12, 24, 48 and 72 h after paediatric intensive care unit admission. The urinary strong ion difference was calculated. The median urinary chloride excretion decreased from 51 mmol/L pre-cardiopulmonary bypass to 25 mmol/L at paediatric intensive care unit admission, and increased from 24 h onwards. Patients with acute kidney injury had lower urinary chloride excretion than those without. The median urinary strong ion difference was 59 mmol/L pre-cardiopulmonary bypass, rose to 131 mmol/L at 24 h and fell to 20 mmol/L at 72 h. The plasma chloride rose from 105 mmol/L pre-cardiopulmonary bypass to a maximum of 109 mmol/L at 24 h. At 24 h the plasma chloride concentration was associated with the presence of acute kidney injury. There was no association between plasma or urinary amino acids and chloride excretion or kidney injury. In conclusion, renal chloride excretion decreased in all patients, although this decrease was more pronounced in patients with acute kidney injury. Our findings may reflect a response of the kidneys to critical illness, and acute kidney injury may make these changes more pronounced. Targeting chloride metabolism may offer treatment approaches to acute kidney injury.
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Affiliation(s)
- Adrian C Mattke
- Department of Paediatric Intensive Care, Queensland Children's Hospital, Brisbane, Australia
- Paediatric Critical Care Research Group, Brisbane, Australia
- Centre for Children's Health Research, Brisbane, Australia
- Child Health Research Centre, The University of Queensland, Brisbane, Australia
- School of Medicine, The University of Queensland, Brisbane, Australia
| | - Kerry E Johnson
- Department of Paediatric Intensive Care, Queensland Children's Hospital, Brisbane, Australia
- Paediatric Critical Care Research Group, Brisbane, Australia
- Centre for Children's Health Research, Brisbane, Australia
- Child Health Research Centre, The University of Queensland, Brisbane, Australia
| | - Krishanti Ariyawansa
- Department of Paediatric Intensive Care, Queensland Children's Hospital, Brisbane, Australia
| | - Peter Trnka
- School of Medicine, The University of Queensland, Brisbane, Australia
- Queensland Child and Adolescent Renal Service, Queensland Children's Hospital, Brisbane, Australia
| | - Prem S Venugopal
- Department for Cardiothoracic Surgery, Queensland Children's Hospital, Brisbane, Australia
| | - David Coman
- School of Medicine, The University of Queensland, Brisbane, Australia
- Wesley Research Institute, The Wesley Hospital, Auchenflower, Australia
- Department for Metabolic Medicine, Queensland Children's Hospital, Brisbane, Australia
| | - Andreas Schibler
- Wesley Research Institute, The Wesley Hospital, Auchenflower, Australia
- St Andrew's War Memorial Hospital, Spring Hill, Brisbane, Australia
- Critical Care Research Group, St Andrew's War Memorial Hospital, Brisbane, Australia
| | - Kristen Gibbons
- Child Health Research Centre, The University of Queensland, Brisbane, Australia
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Heyman SN, Aronson D, Abassi Z. SGLT2 Inhibitors and the Risk of Contrast-Associated Nephropathy Following Angiographic Intervention: Contradictory Concepts and Clinical Outcomes. Int J Mol Sci 2024; 25:10759. [PMID: 39409086 PMCID: PMC11477343 DOI: 10.3390/ijms251910759] [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: 09/05/2024] [Revised: 09/29/2024] [Accepted: 10/03/2024] [Indexed: 10/19/2024] Open
Abstract
The use of SGLT2 inhibitors (SGLT2is) has been found in large clinical studies to slow the progression of chronic kidney disease (CKD) and to lower the risk of acute kidney injury (AKI). Recent reports suggest that SGLT2is may also reduce the likelihood of developing radiocontrast-associated nephropathy (CAN) following contrast-enhanced imaging and intravascular interventions. This review underscores potential pitfalls and confounders in these studies and calls for caution in adopting their conclusions regarding the safety and renoprotective potency of SGLT2is, in particular in patients at high risk, with advanced CKD and hemodynamic instability undergoing coronary intervention. This caution is particularly warranted since both SGLT2is and contrast media intensify medullary hypoxia in the already hypoxic diabetic kidney and their combination may lead to medullary hypoxic damage, a principal component of CAN. Further studies are needed to evaluate this dispute, particularly in patients at high risk, and to reveal whether SGLT2is indeed provide renal protection or are hazardous during contrast-enhanced imaging and vascular interventions.
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Affiliation(s)
- Samuel N. Heyman
- Department of Medicine, Hadassah Hebrew University Hospital, Mt. Scopus, Jerusalem 91240, Israel
| | - Doron Aronson
- Department of Cardiology, Rambam Health Care Campus, Haifa 3109601, Israel;
| | - Zaid Abassi
- Department of Physiology, Bruce Rappaport School of Medicine, Technion, Haifa 3525433, Israel
- Department of Laboratory Medicine, Rambam Health Care Campus, Haifa 3109601, Israel
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Chirico V, Lacquaniti A, Tripodi F, Conti G, Marseglia L, Monardo P, Gitto E, Chimenz R. Acute Kidney Injury in Neonatal Intensive Care Unit: Epidemiology, Diagnosis and Risk Factors. J Clin Med 2024; 13:3446. [PMID: 38929977 PMCID: PMC11205241 DOI: 10.3390/jcm13123446] [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: 04/22/2024] [Revised: 06/02/2024] [Accepted: 06/10/2024] [Indexed: 06/28/2024] Open
Abstract
Acute kidney injury (AKI) is associated with long-term consequences and poor outcomes in the neonatal intensive care unit. Its precocious diagnosis represents one of the hardest challenges in clinical practice due to the lack of sensitive and specific biomarkers. Currently, neonatal AKI is defined with urinary markers and serum creatinine (sCr), with limitations in early detection and individual treatment. Biomarkers and risk factor scores were studied to predict neonatal AKI, to early identify the stage of injury and not the damage and to anticipate late increases in sCr levels, which occurred when the renal function already began to decline. Sepsis is the leading cause of AKI, and sepsis-related AKI is one of the main causes of high mortality. Moreover, preterm neonates, as well as patients with post-neonatal asphyxia or after cardiac surgery, are at a high risk for AKI. Critical patients are frequently exposed to nephrotoxic medications, representing a potentially preventable cause of AKI. This review highlights the definition of neonatal AKI, its diagnosis and new biomarkers available in clinical practice and in the near future. We analyze the risk factors involving patients with AKI, their outcomes and the risk for the transition from acute damage to chronic kidney disease.
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Affiliation(s)
- Valeria Chirico
- Pediatric Nephrology and Dialysis Unit, University Hospital “G. Martino”, 98124 Messina, Italy (F.T.)
| | - Antonio Lacquaniti
- Nephrology and Dialysis Unit, Papardo Hospital, 98158 Messina, Italy (P.M.)
| | - Filippo Tripodi
- Pediatric Nephrology and Dialysis Unit, University Hospital “G. Martino”, 98124 Messina, Italy (F.T.)
| | - Giovanni Conti
- Pediatric Nephrology and Dialysis Unit, University Hospital “G. Martino”, 98124 Messina, Italy (F.T.)
| | - Lucia Marseglia
- Neonatal and Pediatric Intensive Care Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, 98124 Messina, Italy; (L.M.)
| | - Paolo Monardo
- Nephrology and Dialysis Unit, Papardo Hospital, 98158 Messina, Italy (P.M.)
| | - Eloisa Gitto
- Neonatal and Pediatric Intensive Care Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, 98124 Messina, Italy; (L.M.)
| | - Roberto Chimenz
- Pediatric Nephrology and Dialysis Unit, University Hospital “G. Martino”, 98124 Messina, Italy (F.T.)
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Brogi E, Rago R, Forfori F. Evaluation of Renal Function with Urinary NGAL and Doppler Ultrasonography in ICU Patients: A 1-Year Observational Pilot Study. PATHOPHYSIOLOGY 2024; 31:190-196. [PMID: 38651403 PMCID: PMC11036195 DOI: 10.3390/pathophysiology31020015] [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: 02/06/2024] [Revised: 02/23/2024] [Accepted: 04/01/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND We estimated the diagnostic accuracy of urinary NGAL for the diagnosis of AKI. METHODS Urinary NGAL and Creatinine were measured daily for up to 3 days. Doppler ultrasonography was performed within 24 h of admission and for the following 3 days. RESULTS Of the 21 patients, 44% had AKI during their ICU stay. The AKI group presented with higher values of serum Creatinine, renal length, MDRD as well as SAPS II already at admission. Urinary NGAL was significantly higher among patients with AKI and patients AKI-no at T0 (p < 0.0001) and increased steadily on T1 and T2. Urinary NGAL seemed to be a notable diagnostic marker for AKI from the first measurement (T0) with an area under the ROC of 0.93 (95% CI = 0.78-0.99) with a sensitivity of 99%. RRI levels were slightly higher in the AKI group at each time and increased gradually from T0 to T2 but reached statistical significance only at T2 (p = 0.02). Renal length and SAPS II at T0 showed high AuRoc and sensitivity. CONCLUSIONS Urinary NGAL is a valuable marker for AKI in intensive care settings. It seemed that a pre-existing chronic renal disease, the SAPS II and the NGAL at admission represented the principal predictors of AKI.
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Affiliation(s)
- Etrusca Brogi
- Department of Anaesthesia and Intensive Care, University of Pisa, 56126 Pisa, Italy
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Fincher S, Gibbons K, Johnson K, Trnka P, Mattke AC. Urinary Chloride Excretion Postcardiopulmonary Bypass in Pediatric Patients-A Pilot Study. J Pediatr Intensive Care 2024; 13:80-86. [PMID: 38571987 PMCID: PMC10987220 DOI: 10.1055/s-0041-1736549] [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: 06/06/2021] [Accepted: 09/10/2021] [Indexed: 10/20/2022] Open
Abstract
The aim of this study was to describe renal chloride metabolism following cardiopulmonary bypass (CPB) surgery in pediatric patients. A prospective observational trial in a tertiary pediatric intensive care unit (PICU) with 20 recruited patients younger than 2 years following CPB surgery was conducted. Urinary electrolytes, plasma urea, electrolytes, creatinine, and arterial blood gases were collected preoperatively, on admission to PICU and at standardized intervals thereafter. The urinary and plasma strong ion differences (SID) were calculated from these results at each time point. Fluid input and output and electrolyte and drug administration were also recorded. Median chloride administration was 67.7 mmol/kg over the first 24 hours. Urinary chloride (mmol/L; median interquartile range [IQR]) was 30 (19, 52) prior to surgery, 15 (15, 65) on admission, and remained below baseline until 24 hours. Plasma chloride (mmol/L; median [IQR]) was 105 (98, 107) prior to surgery and 101 (101, 106) on admission to PICU. It then increased from baseline, but remained within normal limits, for the remainder of the study. The urinary SID increased from 49.8 (19.1, 87.2) preoperatively to a maximum of 122.7 (92.5, 151.8) at 6 hours, and remained elevated until 48 hours. Plasma and urinary chloride concentrations were not associated with the development of acute kidney injury. Urinary chloride excretion is impaired after CPB. The urinary SID increase associated with the decrease in chloride excretion suggests impaired production and/or excretion of ammonium by the nephron following CPB, with gradual recovery postoperatively.
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Affiliation(s)
- Sophie Fincher
- Department of Pediatric Intensive Care, Queensland Children's Hospital, Brisbane, Australia
- Pediatric Critical Care Research Group, Brisbane, Australia
| | - Kristen Gibbons
- Pediatric Critical Care Research Group, Brisbane, Australia
- Child Health Research Centre, The University of Queensland, Brisbane, Australia
| | - Kerry Johnson
- Department of Pediatric Intensive Care, Queensland Children's Hospital, Brisbane, Australia
- Pediatric Critical Care Research Group, Brisbane, Australia
- Child Health Research Centre, The University of Queensland, Brisbane, Australia
| | - Peter Trnka
- School of Medicine, The University of Queensland, Brisbane, Australia
- Queensland Child and Adolescent Renal Service, Queensland Children's Hospital, Brisbane, Australia
| | - Adrian C. Mattke
- Department of Pediatric Intensive Care, Queensland Children's Hospital, Brisbane, Australia
- Pediatric Critical Care Research Group, Brisbane, Australia
- Child Health Research Centre, The University of Queensland, Brisbane, Australia
- School of Medicine, The University of Queensland, Brisbane, Australia
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Ibrahim WHM, Sabry AA, Abdelmoneim AR, Marzouk HFA, AbdelFattah RM. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (uKIM-1) as markers of active lupus nephritis. Clin Rheumatol 2024; 43:167-174. [PMID: 37516706 PMCID: PMC10774195 DOI: 10.1007/s10067-023-06698-2] [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: 03/09/2023] [Revised: 06/02/2023] [Accepted: 07/02/2023] [Indexed: 07/31/2023]
Abstract
BACKGROUND AND OBJECTIVES Despite much research about lupus nephritis, none of the urinary biomarkers has been proven to be truly reflecting lupus nephritis activity, response to treatment, or prognosis. We aimed to study urinary biomarkers in lupus nephritis and test their relation to kidney damage. PATIENTS AND METHODS Forty patients with systemic lupus erythematosus (SLE) were divided into two graoups: (1) lupus nephritis group with biopsy-proven proliferative lupus nephritis (classes III and IV) and who did not receive immunosuppressive drugs within the preceding 3 months except for glucocorticoids and (2) lupus non-nephritis group with SLE patients without any renal manifestation. We assessed disease activity by the SLE disease activity index. uNGAL, uKim-1, uNGAL to urinary creatinine excretion (mg/dl), and uKim-1 to urinary creatinine excretion were measured in random spot urine samples at the time of renal biopsy and 6 months after the induction therapy. RESULTS The LN group before treatment showed higher levels of uNGAL and uKIM-1 (P-value < 0.001). ROC analysis showed that uNGAL at level of > 59 has a 95 % sensitivity, a 100 % specificity, and an AUC = 0.996 in the ability to diagnose LN. While the uKIM-1 ROC showed that at level of > 1.6, it has an 85 % sensitivity, an 80 % specificity, and an AUC = 0.919. uNGAL and uKIM levels were significantly lower after treatment (P-value < 0.001). No significant correlations were found between urinary markers before and after treatment with other clinical, inflammatory, and serological markers of lupus nephritis. CONCLUSION uNGAL, uKIM, uNGAL/Creat ratio, and uKIM/Creat ratio can be used as a predictor and a marker of disease activity for lupus nephritis. Key Points • Renal biopsy is the current standard for diagnosis of lupus nephritis and none of the urinary biomarkers has been fully concluded to have a diagnostic power to reflect the activity or the response to treatment. • However, based on the finding of the current study, uNGAL, uKIM, uNGAL/Creat ratio, and uKIM/Creat ratio showed significant diagnostic performance and were powerful indices of renal involvement in systemic lupus patients and as markers of disease activity.
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Affiliation(s)
| | - Alaa AbdelAziz Sabry
- Nephrology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Raafat Abdelmoneim
- Nephrology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | | | - Rasha Mahmoud AbdelFattah
- Nephrology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Fan F, Xu P. Global biomarkers trends in acute kidney injury: a bibliometric analysis. Ren Fail 2023; 45:2278300. [PMID: 37994407 PMCID: PMC11001340 DOI: 10.1080/0886022x.2023.2278300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 10/28/2023] [Indexed: 11/24/2023] Open
Abstract
OBJECTIVES Acute kidney injury (AKI) is a common global condition with high morbidity and mortality rates. Biomarkers can aid in the diagnosis, prediction, intervention, and outcome assessment of AKI. This study aimed to summarize the current research status and identify research hotspots for AKI biomarkers using bibliometric analysis. METHODS Relevant original English language articles were retrieved from the Science Citation Index Expanded of the Web of Science Core Collection database, from inception to 31 December 2022. Full records and related cited references from all the documents were collected and analyzed. RESULTS A total of 16368 authors from 3379 institutions in 83 countries/regions contributed to 2916 documents that were published in 712 academic journals. Annual publication output followed exponential growth since 2008. The United States, the University of Pittsburgh, and the American Journal of Physiology-Renal Physiology were the most productive countries, institutions, and journals in terms of research outputs, respectively. The area of interest has shifted from neutrophil gelatinase-associated lipocalin, cell cycle, and tubular damage toward sepsis and COVID-19. Apoptosis, inflammation, and chronic kidney disease have become popular in recent years, and studies on ferroptosis, machine learning, COVID-19, and renal fibrosis will be the focus of future research. IMPLICATIONS This bibliometric study suggests that future research on AKI biomarkers would focus on ferroptosis, renal fibrosis and COVID-19. Artificial intelligence, such as machine learning, maybe the most promising direction for the discovery and validation of AKI biomarkers.
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Affiliation(s)
- Fan Fan
- Department of General Medicine, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Peifeng Xu
- Department of General Medicine, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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Nakai M, Morikawa K, Sasaki T, Kohya R, Yoshida S, Hosoda S, Kubo A, Tokuchi Y, Kitagataya T, Yamada R, Ohara M, Sho T, Suda G, Ogawa K, Sakamoto N. Neutrophil gelatinase-associated lipocalin predicts the efficacy of tolvaptan for ascites in patients with liver cirrhosis. J Gastroenterol 2023; 58:656-667. [PMID: 37103575 DOI: 10.1007/s00535-023-01993-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 04/08/2023] [Indexed: 04/28/2023]
Abstract
BACKGROUND Acute kidney injury (AKI) is associated with liver cirrhosis (LC), water retention, diuretics to treat water retention, and a poor prognosis. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) reportedly predicts a poor prognosis in decompensated LC. This study investigated the usefulness of uNGAL in predicting the short- and long-term effects of tolvaptan (TVP) and the incidence of AKI post-TVP administration. METHODS Of the LC cases with water retention, 86 with available pre-treatment uNGAL were analyzed. A short-term response was defined as weight loss of ≥ 1.5 kg within the first week; a long-term response was defined as a short-term response without early recurrence. The uNGAL usefulness in predicting the short- and long-term effects of TVP and AKI incidence post-TVP administration was investigated. RESULTS Short-term effects of TVP were observed in 52 patients. Of these, 15 patients had an early recurrence. In multivariate analysis, significant short-term predictive factors were C-reactive protein (CRP) < 1.4 mg/dl, uNa/K ratio ≥ 3.51, and uNGAL < 50.2 ng/ml. Patients were classified according to these three cut-off values, with short-term response rates of 92.9%, 68.8%, 26.7%, and 0% for 0, 1, 2, and 3 points, respectively. CRP < 0.94 mg/dl and uNGAL < 50.2 ng/ml were significant factors for predicting the long-term response of TVP. The AKI incidence post-TVP was 8.1% (n = 7) and was significantly higher among those with uNGAL ≥ 38.1 ng/mL. CONCLUSION uNGAL is a useful predictor of the short- and long-term efficacy of TVP and can be useful in predicting AKI incidence post-TVP administration.
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Affiliation(s)
- Masato Nakai
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Takashi Sasaki
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Risako Kohya
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Sonoe Yoshida
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Shunichi Hosoda
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Akinori Kubo
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Yoshimasa Tokuchi
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Takashi Kitagataya
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Ren Yamada
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-shi, Hokkaido, 060-8638, Japan.
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Catanese L, Siwy J, Mischak H, Wendt R, Beige J, Rupprecht H. Recent Advances in Urinary Peptide and Proteomic Biomarkers in Chronic Kidney Disease: A Systematic Review. Int J Mol Sci 2023; 24:ijms24119156. [PMID: 37298105 DOI: 10.3390/ijms24119156] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 05/19/2023] [Accepted: 05/22/2023] [Indexed: 06/12/2023] Open
Abstract
Biomarker development, improvement, and clinical implementation in the context of kidney disease have been a central focus of biomedical research for decades. To this point, only serum creatinine and urinary albumin excretion are well-accepted biomarkers in kidney disease. With their known blind spot in the early stages of kidney impairment and their diagnostic limitations, there is a need for better and more specific biomarkers. With the rise in large-scale analyses of the thousands of peptides in serum or urine samples using mass spectrometry techniques, hopes for biomarker development are high. Advances in proteomic research have led to the discovery of an increasing amount of potential proteomic biomarkers and the identification of candidate biomarkers for clinical implementation in the context of kidney disease management. In this review that strictly follows the PRISMA guidelines, we focus on urinary peptide and especially peptidomic biomarkers emerging from recent research and underline the role of those with the highest potential for clinical implementation. The Web of Science database (all databases) was searched on 17 October 2022, using the search terms "marker *" OR biomarker * AND "renal disease" OR "kidney disease" AND "proteome *" OR "peptid *" AND "urin *". English, full-text, original articles on humans published within the last 5 years were included, which had been cited at least five times per year. Studies based on animal models, renal transplant studies, metabolite studies, studies on miRNA, and studies on exosomal vesicles were excluded, focusing on urinary peptide biomarkers. The described search led to the identification of 3668 articles and the application of inclusion and exclusion criteria, as well as abstract and consecutive full-text analyses of three independent authors to reach a final number of 62 studies for this manuscript. The 62 manuscripts encompassed eight established single peptide biomarkers and several proteomic classifiers, including CKD273 and IgAN237. This review provides a summary of the recent evidence on single peptide urinary biomarkers in CKD, while emphasizing the increasing role of proteomic biomarker research with new research on established and new proteomic biomarkers. Lessons learned from the last 5 years in this review might encourage future studies, hopefully resulting in the routine clinical applicability of new biomarkers.
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Affiliation(s)
- Lorenzo Catanese
- Department of Nephrology, Angiology and Rheumatology, Klinikum Bayreuth GmbH, 95447 Bayreuth, Germany
- Kuratorium for Dialysis and Transplantation (KfH), 95445 Bayreuth, Germany
- Medizincampus Oberfranken, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Justyna Siwy
- Mosaiques Diagnostics GmbH, 30659 Hannover, Germany
| | | | - Ralph Wendt
- Department of Nephrology, St. Georg Hospital Leipzig, 04129 Leipzig, Germany
| | - Joachim Beige
- Department of Nephrology, St. Georg Hospital Leipzig, 04129 Leipzig, Germany
- Department of Internal Medicine II, Martin-Luther-University Halle/Wittenberg, 06108 Halle/Saale, Germany
- Kuratorium for Dialysis and Transplantation (KfH), 04129 Leipzig, Germany
| | - Harald Rupprecht
- Department of Nephrology, Angiology and Rheumatology, Klinikum Bayreuth GmbH, 95447 Bayreuth, Germany
- Kuratorium for Dialysis and Transplantation (KfH), 95445 Bayreuth, Germany
- Medizincampus Oberfranken, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany
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11
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Cheng AS, Li X. The Potential Biotherapeutic Targets of Contrast-Induced Acute Kidney Injury. Int J Mol Sci 2023; 24:8254. [PMID: 37175958 PMCID: PMC10178966 DOI: 10.3390/ijms24098254] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 04/27/2023] [Accepted: 04/28/2023] [Indexed: 05/15/2023] Open
Abstract
Contrast-induced acute kidney injury (CI-AKI) is manifested by an abrupt decline in kidney function as a consequence of intravascular exposure to contrast media. With the increased applicability of medical imaging and interventional procedures that utilize contrast media for clinical diagnosis, CI-AKI is becoming the leading cause of renal dysfunction. The pathophysiological mechanism associated with CI-AKI involves renal medullary hypoxia, the direct toxicity of contrast agents, oxidative stress, apoptosis, inflammation, and epigenetic regulation. To date, there is no effective therapy for CI-AKI, except for the development of strategies that could reduce the toxicity profiles of contrast media. While most of these strategies have failed, evidence has shown that the proper use of personalized hydration, contrast medium, and high-dose statins may reduce the occurrence of CI-AKI. However, adequate risk predication and attempts to develop preventive strategies can be considered as the key determinants that can help eliminate CI-AKI. Additionally, a deeper understanding of the pathophysiological mechanism of CI-AKI is crucial to uncover molecular targets for the prevention of CI-AKI. This review has taken a step further to solidify the current known molecular mechanisms of CI-AKI and elaborate the biomarkers that are used to detect early-stage CI-AKI. On this foundation, this review will analyze the molecular targets relating to apoptosis, inflammation, oxidative stress, and epigenetics, and, thus, provide a strong rationale for therapeutic intervention in the prevention of CI-AKI.
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Affiliation(s)
- Alice Shasha Cheng
- Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA;
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
| | - Xiaogang Li
- Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA;
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
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12
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Abbas Q, Laghari P, Jurair H, Nafis J, Saeed B, Qazi MF, Saleem A, Khan AHH, Haque A. Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Acute Kidney Injury in Children With Shock: A Prospective Study. Cureus 2023; 15:e34407. [PMID: 36874735 PMCID: PMC9977468 DOI: 10.7759/cureus.34407] [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] [Accepted: 01/29/2023] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND The current definition of acute kidney injury (AKI) is based on serum creatinine (SrCr) and urine output, limited by delayed identification of such patients. Plasma neutrophil gelatinase-associated lipocalin (NGAL) is considered an early diagnostic and highly predictive biomarker of AKI. OBJECTIVE To determine the diagnostic accuracy of NGAL for AKI compared with creatinine clearance for early detection of AKI in children with shock receiving inotropic support. METHODS Critically ill children requiring inotropic support in the pediatric intensive care unit were enrolled prospectively. SrCr and NGAL values were obtained three times at six, 12, and 48 hours after vasopressor initiation. Patients with AKI were defined as having loss of >25% renal function based on creatinine clearance within 48 hours. NGAL level of more than 150 ng/dl was suggestive of the diagnosis of AKI. Receiver operator characteristic curves were generated for NGAL and SrCr to compare the predictive ability of both at 0, 12, and 48 hours of starting vasopressor support. Results: A total of 94 patients were enrolled. The mean age was 43±50.95 months. Most common primary diagnoses were related to the cardiovascular system (46%). Twenty-nine patients (31%) died during the hospital stay. Thirty-four patients (36%) developed AKI within 48 hours following shock. The area under the curve (AUC) for NGAL at a cutoff of 150 ng/ml was 0.70, 0.74, and 0.73 at six-hour, 12-hour, and 48-hour follow-up, respectively. NGAL had a sensitivity of 85.3% and specificity of 50% at 0 hours of follow-up for diagnosis of AKI. CONCLUSION Serum NGAL has better sensitivity and AUC compared to SrCr for early diagnosis of AKI in children admitted with shock.
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Affiliation(s)
- Qalab Abbas
- Department of Pediatrics and Child Health, Aga Khan University Hospital, Karachi, PAK
| | - Parveen Laghari
- Department of Pediatrics and Child Health, Aga Khan University Hospital, Karachi, PAK
| | - Humaira Jurair
- Department of Pediatrics Pediatric Intensive Care Unit (PICU), The Indus Hospital, Karachi, PAK
| | - Javeria Nafis
- Department of Community Health Sciences, Aga Khan University Hospital, Karachi, PAK
| | - Bushra Saeed
- Department of Pediatrics and Child Health, Aga Khan University Hospital, Karashi, PAK
| | - Muhammad F Qazi
- Department of Pediatrics and Child Health, Aga Khan University Hospital, Karachi, PAK
| | - Ali Saleem
- Pediatrics, Aga Khan University Hospital, Karachi, PAK
| | - Aysha Habib H Khan
- Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, PAK
| | - Anwar Haque
- Pediatrics, The Indus Hospital, Karachi, PAK
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13
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Zhang Q, Li Y, Hu Q, Xie R, Zhou W, Liu X, Wang Y. Smartphone surface plasmon resonance imaging for the simultaneous and sensitive detection of acute kidney injury biomarkers with noninvasive urinalysis. LAB ON A CHIP 2022; 22:4941-4949. [PMID: 36411971 DOI: 10.1039/d2lc00417h] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
A surface plasmon resonance imaging (SPRi) platform integrated with a smartphone was constructed for the simultaneous and sensitive detection of acute kidney injury (AKI) biomarkers. The smartphone SPRi platform was developed without the requirement of additional light and power sources. The LED flash of the smartphone was used as the light source for the excitation of surface plasmon resonance of a gold sensor chip based on the Kretschmann configuration, while the reflected light was collected by the camera of the smartphone. This smartphone SPRi system was conveniently fabricated by 3D printing and showed a sensitivity of 1.78 × 10-5 refractive index unit (RIU). In addition, based on a magnetic nanoparticle-enhanced sandwich immunoassay, the smartphone SPRi system with a gold array chip was employed for the detection of multiple AKI biomarkers, with a low limit of detection (LOD) of 0.19 ng ml-1, 0.51 ng ml-1 and 0.7 ng ml-1 for the simultaneous detection of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18) and retinol-binding protein (RBP) in urine, respectively. The biosensors demonstrated high specificity and sensitivity for the simultaneous detection of multiple AKI biomarkers in PBST and urine. The smartphone SPRi system provided a portable and cost-effective platform for point-of-care diagnosis, in-field healthcare and environmental monitoring.
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Affiliation(s)
- Qingwen Zhang
- School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325001 China.
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001 China.
| | - Yang Li
- School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325001 China.
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000 China
| | - Qianqian Hu
- Beijing Chaoyang District Ecological and Environmental Monitoring Center, Beijing, 100123 China
| | - Ruifeng Xie
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001 China.
| | - Wenjing Zhou
- School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325001 China.
| | - Xiaohu Liu
- School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325001 China.
| | - Yi Wang
- School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325001 China.
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001 China.
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14
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Sun Q, Kang Z, Li Z, Xun M. Urinary NGAL, IGFBP-7, and TIMP-2: novel biomarkers to predict contrast medium-induced acute kidney injury in children. Ren Fail 2022; 44:1201-1206. [PMID: 36120960 PMCID: PMC9518296 DOI: 10.1080/0886022x.2022.2075277] [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: 11/21/2022] Open
Abstract
Background Serum creatinine (SCr) is unreliable in detecting acute changes in kidney function. Early recognition of contrast-induced acute kidney injury (CI-AKI) can provide better opportunities for preventive interventions. Therefore, the purpose of this study is to examine the value of the combined detection of urinary neutrophil gelatinase-associated lipocalin (NGAL), insulin-like growth factor binding protein-7 (IGFBP-7), and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the early diagnosis of children with CI-AKI. Methods A prospective, single-center clinical trial was performed and included 172 children aged 0–18 years. The dynamic changes of urinary NGAL, IGFBP-7, and TIMP-2 levels in children with intravascular injection of contrast medium were investigated to determine whether they can diagnose CI-AKI early. Results CI-AKI occurred in 20 of 137 enrolled patients, and the incidence was 14.59%. In the CI-AKI group, urinary levels of NGAL, IGFBP-7, TIMP-2, and [IGFBP-7]*[TIMP-2] were significantly increased 2 h after angiography and remained at high levels at 6 h. Using a cutoff value of 36.274 ng/mL, the specificity was 70.0%, and the sensitivity was 68.4% for the prediction of CI-AKI, which was excellent for urinary NGAL. When both urinary IGFBP-7 and TIMP-2 were used together, urinary [IGFBP-7]*[TIMP-2] at 0.417(ng/mL)2/1000 was regarded as the cutoff value. The specificity was 80.0%, and the sensitivity was 81.2%. Conclusions NGAL, IGFBP-7, and TIMP-2 concentrations in the urine of children after receiving injections of contrast medium increased faster than SCr and had good clinical value for the early diagnosis of CI-AKI in children. The combination of IGFBP-7 and TIMP-2 was better than either analyte alone.
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Affiliation(s)
- Qianliang Sun
- College of Pediatrics, University of South China/Children's Hospital of Hunan Province, Changsha, P.R. China
| | - Zhijuan Kang
- College of Pediatrics, University of South China/Children's Hospital of Hunan Province, Changsha, P.R. China
| | - Zhihui Li
- College of Pediatrics, University of South China/Children's Hospital of Hunan Province, Changsha, P.R. China
| | - Mai Xun
- College of Pediatrics, University of South China/Children's Hospital of Hunan Province, Changsha, P.R. China
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15
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Marakala V. Neutrophil Gelatinase-Associated Lipocalin (NGAL) in kidney injury- A systematic review. Clin Chim Acta 2022; 536:135-141. [PMID: 36150522 DOI: 10.1016/j.cca.2022.08.029] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/26/2022] [Accepted: 08/30/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND Neutrophil Gelatinase Associated Lipocalin (NGAL) is a secretory protein of neutrophils that can be found both in plasma and urine. Previous works have demonstrated a valuable marker for the early detection of acute kidney injury. In this systematic review, we aimed to assess whether NGAL could be helpful in the diagnosis and prognosis of systemic diseases with kidney involvement. METHODS MEDLINE, PubMed, and EMBASE databases were searched for NGAL, described as a human biomarker for diseases (total: 1690). Specifically, included studies describing the use of NGAL for determining kidney injury outcomes and other conditions associated with kidney dysfunction, including cardiovascular diseases, cardiac surgery, and critically ill systemic disorders. RESULTS A total of 24 validated studies were included in the systemic review after applying the exclusion criteria. In all these studies, NGAL appeared to have a predictive value irrespective of age, from newborn to 78 years. The results indicate that NGAL levels can accurately predict the outcome and severity of acute kidney injury occur in several disease processes, including contrast-induced AKI during cardiac surgery, kidney transplant rejection, chronic heart failure, and systemic inflammation in critically ill patients, even though the significance of NGAL is highly variable across studies. Very high plasma NGAL levels were observed in the patients before the acute rejection of the kidney, indicating the prognostic potential of the NGAL. Specifically, the assays conducted before 72 hrs provided a significant predictive value. CONCLUSION Urinary and serum NGAL appears to be an independent predictor of not only kidney complications but also cardiovascular and liver-related diseases. The kidney is also involved in pathogenesis.
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Affiliation(s)
- Vijaya Marakala
- Department of Basic Medical Sciences, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.
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16
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Saoin S, Arunyanak N, Muangchan P, Boonkrai C, Pisitkun T, Kloypan C, Nangola S. Bicistronic vector-based procedure to measure correlative expression and bacteriostatic activity of recombinant neutrophil gelatinase-associated lipocalin. BIOTECHNOL BIOTEC EQ 2022. [DOI: 10.1080/13102818.2022.2101943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022] Open
Affiliation(s)
- Somphot Saoin
- Division of Clinical Immunology and Transfusion Science, Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao, Thailand
- Unit of Excellence in Integrative Molecular Biomedicine, School of Allied Health Sciences, University of Phayao, Phayao, Thailand
| | - Naphatswan Arunyanak
- Division of Clinical Immunology and Transfusion Science, Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao, Thailand
| | - Pornuma Muangchan
- Division of Clinical Immunology and Transfusion Science, Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao, Thailand
| | - Chatikorn Boonkrai
- Center of Excellence in Systems Biology, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Trairak Pisitkun
- Center of Excellence in Systems Biology, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Chiraphat Kloypan
- Division of Clinical Immunology and Transfusion Science, Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao, Thailand
- Unit of Excellence in Integrative Molecular Biomedicine, School of Allied Health Sciences, University of Phayao, Phayao, Thailand
| | - Sawitree Nangola
- Division of Clinical Immunology and Transfusion Science, Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao, Thailand
- Unit of Excellence in Integrative Molecular Biomedicine, School of Allied Health Sciences, University of Phayao, Phayao, Thailand
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17
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Prüllage ML, Schwendenwein I, Eberspächer-Schweda E, Kneissl S. Does intravenous contrast medium administration result in altered renal biomarkers? A study in clinically stable cats with and without azotemia. J Feline Med Surg 2022; 24:565-579. [PMID: 34493101 PMCID: PMC11104225 DOI: 10.1177/1098612x211038535] [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: 11/17/2022]
Abstract
OBJECTIVES The aim of this study was to determine the prevalence of post-contrast acute kidney injury or comparable side effects on kidney function in cats receiving the non-ionic, iodinated agent ioversol and/or paramagnetic agent gadoteric acid. METHODS Fifty-two animals were divided into four groups on the basis of contrast medium administration for imaging: ioversol (n = 27), gadoteric acid (n = 12), dual contrast media (n = 4) or control, which received an infusion of isotone intravenous fluids only during anaesthesia (n = 9). Blood and urine samples were obtained three times after contrast administration and compared with values obtained prior to administration of the contrast medium. Creatinine (<1.60 mg/dl), symmetric dimethylarginine (SDMA; ⩽14 μg/dl), urine protein:creatinine ratio (UPC; <0.2) and critical differences for creatinine (<0.3 mg/dl) and SDMA (<5.98 μg/dl) were measured. RESULTS No significant short-term effects on mean creatinine, SDMA and UPC measurements were seen. Borderline proteinuria (UPC, 0.2-0.4) was detected in 11.4% of cases after contrast media administration. A UPC of more than 0.2 in five cases indicated that contrast media may affect kidney function, leading to (transient) proteinuria. CONCLUSIONS AND RELEVANCE This study found no side effect on renal function following the administration of ioversol or gadoteric acid, provided patients were adequately hydrated. However, the clinical relevance of proteinuria in some cats needs to be evaluated in future studies.
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Affiliation(s)
- Maria Laura Prüllage
- Diagnostic Imaging, Department of Companion Animals and Horses, University of Veterinary Medicine, Vienna, Austria
| | - Ilse Schwendenwein
- Clinical Pathology Platform, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria
| | - Eva Eberspächer-Schweda
- Anaesthesiology and Perioperative Intensive-Care Medicine, Department of Companion Animals and Horses, University of Veterinary Medicine, Vienna, Austria
| | - Sibylle Kneissl
- Diagnostic Imaging, Department of Companion Animals and Horses, University of Veterinary Medicine, Vienna, Austria
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18
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van der Molen AJ, Dekkers IA, Bedioune I, Darmon-Kern E. A systematic review of the incidence of hypersensitivity reactions and post-contrast acute kidney injury after ioversol: part 2-intra-arterial administration. Eur Radiol 2022; 32:5546-5558. [PMID: 35312791 PMCID: PMC9279267 DOI: 10.1007/s00330-022-08637-2] [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: 09/15/2021] [Revised: 12/03/2021] [Accepted: 01/03/2022] [Indexed: 11/21/2022]
Abstract
Objectives To evaluate the incidence of adverse drug reactions (ADRs), including hypersensitivity reactions (HSRs) and post-contrast acute kidney injury (PC-AKI), after intra-arterial (IA) administration of ioversol. Methods and materials A systematic literature search was performed (1980–2021) and studies documenting IA use of ioversol, and reporting safety outcomes were selected. Key information on study design, patients’ characteristics, indication, dose, and type of safety outcome were extracted. Results Twenty-eight studies (including two pediatric studies) with 8373 patients exposed to IA ioversol were selected. Studies were highly heterogenous in terms of design, PC-AKI definition, and studied population. PC-AKI incidence after coronary angiography was 7.5–21.9% in a general population, 4.0-26.4% in diabetic patients, and 5.5–28.9% in patients with chronic kidney disease (CKD). PC-AKI requiring dialysis was rare and reported mainly in patients with severe CKD. No significant differences in PC-AKI rates were shown in studies comparing different iodinated contrast media (ICM). Based on seven studies of ioversol clinical development, the overall ADR incidence was 1.6%, comparable to that reported with other non-ionic ICM. Pediatric data were scarce with only one study reporting on PC-AKI incidence (12%), and one reporting on ADR incidence (0.09%), both after coronary angiography. Conclusions After ioversol IA administration, PC-AKI incidence was highly variable between studies, likely reflecting the heterogeneity of the included study populations, and appeared comparable to that reported with other ICM. The rate of other ADRs appears to be low. Well-designed studies are needed for a better comparison with other ICM. Key Points • PC-AKI incidence after IA administration of ioversol appears to be comparable to that of other ICM, despite the high variability between studies. • The need for dialysis after IA administration of ioversol is rare. • No obvious difference was found regarding the safety profile of ioversol between IA and IV administration.
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Affiliation(s)
- Aart J van der Molen
- Contrast Media Safety Research Group, Department of Radiology C-2S, Leiden University Medical Center, Albinusdreef 2, NL-2333, ZA, Leiden, The Netherlands.
| | - Ilona A Dekkers
- Contrast Media Safety Research Group, Department of Radiology C-2S, Leiden University Medical Center, Albinusdreef 2, NL-2333, ZA, Leiden, The Netherlands
| | - Ibrahim Bedioune
- Clinical Development Department, Guerbet, Roissy CDG Cedex, France
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Loureiro ACC, Nocrato GF, Correia ALL, de Matos RS, Filho JCCN, Daher EDF, Pinto FHM, de Oliveira AC, Ceccatto VM, Fortunato RS, de Carvalho DP. Serum and Urinary Neutrophil Gelatinase-Associated Lipocalin Are Not Associated With Serum Redox Parameters in Amateur Athletes After an Ultramarathon. Front Physiol 2022; 13:811514. [PMID: 35370771 PMCID: PMC8970054 DOI: 10.3389/fphys.2022.811514] [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] [Received: 11/08/2021] [Accepted: 01/31/2022] [Indexed: 11/13/2022] Open
Abstract
Objective To evaluate the relationship between oxidative stress and NGAL levels in blood and urine of amateur athletes after participating in a 100 km ultramarathon. Methodology The sample was composed of seven athletes, submitted to anthropometric assessment, cardiopulmonary exercise test, collection of urine and blood, measurement of body weight. The rate of perceived exertion (RPE), competition duration, heart rate (HR), energy expenditure and oxygen consumption (V'O2") were also measured during the event. The energy consumption during the race was verified at its end. The analyses were based on the means (M) and respective standard deviations (SD), with statistical significance set at 5% (p < 0.05). Paired t-test was used for comparison between the periods before and after the competition, and Pearson's correlation coefficient was used to measure the linear correlation between quantitative variables. Results Body mass index (BMI) of the sample was 25.75 kg/m2 ± 3.20, body fat percentage 18.54% ± 4.35% and V'O2"max 48.87% ± 4.78. Glucose, cortisol, and neutrophil gelatinase-associated lipocalin (NGAL) (p < 0.01) as well as glutathione peroxidase (GPx) active were higher after the race when compared to basal values. Moreover, lactate, creatinine, microalbuminuria, and glomerular filtration rate (GFR) (p < 0.001) were also higher after the race. After the competition, there was a significant correlation only between serum NGAL and creatinine, which was classified as strong and positive (r: 0.77; p < 0.05). There was a significant reduction (p < 0.05) of body weight after the event (72.40 kg ± 9.78) compared to before it (73.98 kg ± 10.25). In addition, we found an increase of RPE (p < 0.001) after the race. The competition lasted 820.60 min (±117.00), with a 127.85 bpm (±12.02) HR, a 2209.72 kcal ± 951.97 energy consumption, 7837.16 kcal ± 195.71 energy expenditure, and 28.78 ml/kg/min-1 (±4.66) relative V'O2"max. Conclusion The lack of correlation between oxidative stress biomarkers and serum and urine NGAL suggests that NGAL is more sensitive to inflammatory processes than to ROS levels.
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Affiliation(s)
| | | | | | - Robson Salviano de Matos
- Department of Clinical Medicine at the Federal University of Ceará, Ceará Federal University, Fortaleza, Brazil
| | | | | | | | | | | | - Rodrigo Soares Fortunato
- Carlos Chagas Filho Biophysics Institute, Rio de Janeiro Federal University, Rio de Janeiro, Brazil
| | - Denise Pires de Carvalho
- Carlos Chagas Filho Biophysics Institute, Rio de Janeiro Federal University, Rio de Janeiro, Brazil
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20
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Bhardwaj A, Narain U, Gupta A. PROGNOSTIC UTILITY OF NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN IN CARDIAC ICU: A PROSPECTIVE STUDY. Indian Heart J 2022; 74:249-250. [PMID: 35331722 PMCID: PMC9243608 DOI: 10.1016/j.ihj.2022.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 03/07/2022] [Accepted: 03/11/2022] [Indexed: 11/12/2022] Open
Abstract
Our study aims to evaluate the role of neutrophil gelatinase associated lipocalin (NGAL) as an early surrogate marker in predicting acute kidney injury (AKI) and mortality in cardiac ICU patients. The study was conducted at SRN Hospital, excluding those with known renal diseases. Out of 152 patients, 56 developed AKI (cases) and 96 were our controls. Higher NGAL was associated with increased mortality rates (P = 0.0201 and 0.0255 for serum and urinary NGAL respectively). Our study concluded that NGAL measurement at admission may be a boon in improving the outcome of cardiac ICU patients.
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21
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Skalsky K, Shiyovich A, Steinmetz T, Kornowski R. Chronic Renal Failure and Cardiovascular Disease: A Comprehensive Appraisal. J Clin Med 2022; 11:1335. [PMID: 35268426 PMCID: PMC8911484 DOI: 10.3390/jcm11051335] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 02/23/2022] [Accepted: 02/24/2022] [Indexed: 02/01/2023] Open
Abstract
Coronary artery disease is highly prevalent in patients with chronic kidney disease. The concomitant renal disease often poses a major challenge in decision making as symptoms, cardiac biomarkers and noninvasive studies for evaluation of myocardial ischemia have different sensitivity and specificity thresholds in this specific population. Moreover, the effectiveness and safety of intervention and medical treatment in those patients is of great doubt as most clinical studies exclude patients with advance CKD. In the present paper, we discuss and review the literature in the diagnosis, treatment and prevention of CAD in the acute and chronic setting, in patients with CKD.
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Affiliation(s)
- Keren Skalsky
- Department of Cardiology, Rabin Medical Center, Petah Tikva 4941492, Israel; (A.S.); (R.K.)
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel;
| | - Arthur Shiyovich
- Department of Cardiology, Rabin Medical Center, Petah Tikva 4941492, Israel; (A.S.); (R.K.)
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel;
| | - Tali Steinmetz
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel;
- Department of Nephrology, Rabin Medical Center, Petah Tikva 4941492, Israel
| | - Ran Kornowski
- Department of Cardiology, Rabin Medical Center, Petah Tikva 4941492, Israel; (A.S.); (R.K.)
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel;
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22
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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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Renal and Inflammation Markers-Renalase, Cystatin C, and NGAL Levels in Asymptomatic and Symptomatic SARS-CoV-2 Infection in a One-Month Follow-Up Study. Diagnostics (Basel) 2022; 12:diagnostics12010108. [PMID: 35054276 PMCID: PMC8774569 DOI: 10.3390/diagnostics12010108] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 12/30/2021] [Accepted: 01/01/2022] [Indexed: 01/08/2023] Open
Abstract
The aim of our study was to evaluate the influence of asymptomatic infection and the occurrence of symptomatic COVID-19 on specific biochemical, renal, and immune parameters—renalase, neutrophil gelatinase-associated lipocalin (NGAL) cystatin C (CysC), and creatinine—and their weekly fluctuations during a one-month observation period in COVID-19 patients admitted to hospital. The study involved 86 individuals: 30 patients with diagnosed COVID-19, 28 people with asymptomatic infection confirmed with IgG antibodies—the IG(+) group—and 28 individuals without any (IgG, IgE) anti-SARS-CoV-2 antibodies—the IG(−) group. In the COVID-19 group, blood was drawn four times: (1) on day 0/1 after admission to hospital (C1 group), (2) 7 days later (C7 group), (3) 14 days later (C14 group), and (4) 28 days later (C28 group). In the IG(−) and IG(+) groups, blood was drawn once. There were no significant differences in creatinine, Cys C, and uric acid between any of the analyzed groups. NGAL levels were significantly higher in IG(+) and at all time-points in the COVID-19 groups than in controls. A similar observation was made for renalase at the C7, C14, and C28 time-points. Plasma renalase, NGAL, and CysC are unrelated to kidney function in non-critically ill COVID-19 patients and those with asymptomatic infection. Renalase and NGAL are most likely related to the activation of the immune system rather than kidney function. Asymptomatic SARS-CoV-2 infection causes a rise in plasma NGAL levels similar to those observed in symptomatic COVID-19 patients. Therefore, more attention should be paid to tracking and monitoring the health of these people.
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Sahu A, Goel P, Khanna R, Kumar S, Kapoor A, Tewari S, Garg N. Neutrophil gelatinase–associated lipocalin as a marker for contrast-induced nephropathy in patients undergoing percutaneous coronary intervention: A prospective observational analysis. Indian J Nephrol 2022; 32:247-255. [PMID: 35814328 PMCID: PMC9267084 DOI: 10.4103/ijn.ijn_418_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 07/14/2021] [Accepted: 08/30/2021] [Indexed: 12/01/2022] Open
Abstract
Introduction: Incidence of contrast-induced nephropathy (CIN) post percutaneous coronary intervention (PCI) varies between 5% and 20%. Neutrophil gelatinase–associated lipocalin (NGAL) is a sensitive marker for acute kidney injury. Data regarding the predictive accuracy of NGAL in Indian patients undergoing PCI is sparse. Methods: A total of 212 consecutive “all-comer” patients, undergoing PCI from March 2015 to April 2016 were recruited in this single-center observational study. Plasma NGAL levels were measured at 4 hours post PCI using commercially available enzyme-linked immunosorbent assay (Triage® Alere™, San Diego, CA, USA). Results: Twenty-five (11.8%) patients developed CIN. The 4-hour post-PCI plasma NGAL levels were significantly higher in patients with CIN than without (400.6 ± 269.3 ng/mL vs. 109.8 ± 68.0 ng/mL, P < 0.0001). Patients developing CIN had higher age, low estimated glomerular filtration rate (eGFR), and higher contrast volume usage during PCI. After adjusting for confounding factors, diabetes mellitus (adjusted odds ratio [AOR] 3.04; P = 0.039; 95% confidence interval [CI]: 1.06–8.73), hypotension at presentation (AOR 24.84; P < 0.0001; 95% CI: 4.65–132.83), and multi-staged PCI (AOR 13.45; P < 0.0001; 95% CI: 4.54–39.79) were found to independently predict the development of CIN. NGAL levels significantly correlated with age (r = 0.149, P = 0.031), eGFR (r = −0.385, P < 0.0001), hemoglobin (r = −0.214, P = 0.002), contrast volume (r = 0.185, P = 0.007), and 48-hour post-PCI serum creatinine levels (r = 0.334, P < 0.0001). At a cutoff of 256.5 ng/mL, plasma NGAL had a sensitivity of 68% and a specificity of 95.2% (area under the curve = 0.878; P < 0.0001; 95% CI: 0.801–0.955) to predict the occurrence of CIN. Conclusions: Plasma NGAL is an early and highly predictive biomarker of CIN in patients undergoing PCI. Patients having diabetes, hypotension at presentation and those undergoing second-stage procedures are at a high risk of developing CIN after PCI.
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Lupu L, Abukatash H, Banai A, Rozenfeld KL, Lewit D, Merdler I, Loewenstein I, Bornstein G, Banai S, Shacham Y. Relation of Baseline Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels and Contrast-Induced Nephropathy following Percutaneous Coronary Intervention among Chronic Kidney Disease Patients. J Clin Med 2021; 10:jcm10225403. [PMID: 34830685 PMCID: PMC8626017 DOI: 10.3390/jcm10225403] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/04/2021] [Accepted: 11/17/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The risk of contrast-induced acute kidney injury (CI-AKI) following coronary intervention is particularly high among patients with chronic kidney disease (CKD). Among these patients, baseline neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular damage, reflects the severity of renal impairment. We evaluated whether the baseline serum NGAL level may be a marker for the development of CI-AKI following percutaneous coronary intervention (PCI). METHODS Eighty-eight CKD patients treated with PCI were included. Serum NGAL levels were drawn upon hospital admission. Receiver operator characteristic (ROC) methods were used to identify the optimal sensitivity and specificity for the observed NGAL level compared with the estimated glomerular filtration rate (eGFR) calculated for patients with CI-AKI. RESULTS Overall CI-AKI incidence was 43%. Baseline serum NGAL levels were significantly higher in patients with CI-AKI than in patients without CI-AKI (150 vs. 103 ng/mL, p < 0.001). According to the ROC curve, baseline NGAL levels performed better than eGFR to predict CI-AKI (AUC 0.753 vs. 0.604), with the optimal cutoff value for baseline NGAL to predict CI-AKI being 127 ng/mL (sensitivity of 68% and specificity of 68%, p < 0.001). In a multivariate logistic regression model, the NGAL level >127 ng/mL ng/mL was independently associated with CI-AKI (HR 9.84, 95% CI: 1.96-40.3; p = 0.01). CONCLUSION Baseline serum NGAL levels in CKD patients may identify a high-risk population for CI-AKI following PCI. Further studies on larger populations are required to validate the potential utility of NGAL measurements in monitoring specific CKD-associated conditions.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Yacov Shacham
- Correspondence: ; Tel.: +972-3-6973222 or +972-52-4262101; Fax: +972-3-6973704
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Williams V, Jayashree M, Nallasamy K, Dayal D, Rawat A, Attri SV. Serial urinary neutrophil gelatinase associated lipocalin in pediatric diabetic ketoacidosis with acute kidney injury. Clin Diabetes Endocrinol 2021; 7:20. [PMID: 34719396 PMCID: PMC8559408 DOI: 10.1186/s40842-021-00133-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 09/27/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Acute kidney injury (AKI) due to Diabetic Ketoacidosis (DKA) is rather common. Novel biomarkers to diagnose AKI are being increasingly used in different settings. The use of urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in predicting persistent AKI in pediatric DKA cases is still not thoroughly investigated. METHODS This was a secondary analysis of Saline versus Plasma-Lyte in Ketoacidosis (SPinK) trial data; 66 children (> 1 month-12 years) with DKA, defined by the International Society for Pediatric and Adolescent Diabetes (ISPAD), were analyzed. Children with cerebral edema, chronic kidney disease and those who received pre-referral fluids and/or insulin were excluded. uNGAL and urine NGAL-creatinine ratio (uNCR) at 0 and 24 h were measured in all. Persistent AKI was defined as a composite outcome of continuance of AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or 3 beyond 48 h from AKI onset, progression of AKI from either KDIGO stage 0 or 1 to a worse stage, need of renal replacement therapy or death. MAIN OUTCOMES Thirty-five (53%) children had AKI at admission; 32 (91.4%) resolved within 48 h. uNGAL was significantly higher in the AKI group at admission [79.8 ± 27.2 vs 54.6 ± 22.0, p = 0.0002] and at 24 h [61.4 ± 28.3 vs 20.2 ± 14.5, p = 0.0003]. Similar trend was observed with uNCR at admission [6.7 ± 3.7 vs 4.1 ± 2.6, p = 0.002] and at 24 h [6.3 ± 2.5 vs 1.2 ± 1.0, p = 0.01]. Furthermore, uNGAL at admission showed a moderate positive linear correlation with serum creatinine. Additionally, elevated uNGAL at 0 and 24 h correlated with corresponding KDIGO stages. Admission uNGAL >88 ng/ml and uNCR of >11.3 ng/mg had a sensitivity of 66% and 67%, specificity of 76% and 95%, and Area under the receiver operating characteristic curve (AUC) of 0.78 and 0.89 respectively for predicting persistent AKI at 48 h. CONCLUSIONS Majority of AKI resolved with fluid therapy. While uNGAL and uNCR both correlated with serum creatinine and AKI stages, serial uNCR was a better predictor of persistent AKI than uNGAL alone. However, feasibility of routine uNGAL measurement to predict persistent AKI in DKA needs further elucidation. TRIAL REGISTRATION This was a secondary analysis of the data of SPinK trial [CTRI/2018/05/014042 ( ctri.nic.in )].
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Affiliation(s)
- Vijai Williams
- Division of Pediatric Intensive Care, Department of Critical Care, Sheikh Khalifa Medical City (SKMC), Abu Dhabi, United Arab Emirates
| | - Muralidharan Jayashree
- Division of Pediatric Emergency and Intensive Care, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Karthi Nallasamy
- Division of Pediatric Emergency and Intensive Care, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Devi Dayal
- Division of Pediatric Endocrinology, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Amit Rawat
- Division of Pediatric Allergy and Immunology, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Savita Verma Attri
- Division of Pediatric Biochemistry, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Fuhrman D. The use of diagnostic tools for pediatric AKI: applying the current evidence to the bedside. Pediatr Nephrol 2021; 36:3529-3537. [PMID: 33492454 PMCID: PMC8813176 DOI: 10.1007/s00467-021-04940-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 12/08/2020] [Accepted: 01/08/2021] [Indexed: 12/17/2022]
Abstract
Given the known deleterious consequences of acute kidney injury (AKI), exciting recent research efforts have focused on developing strategies for the earlier recognition of AKI in the pediatric population. Recognizing the limitations of serum creatinine, investigators have focused on the study of novel biomarkers and practical bedside tools for identifying patients at risk for AKI prior to a rise in serum creatinine. In PubMed, there are presently over 30 original research papers exploring the use of pediatric AKI risk prediction tools in just the last 2 years. The following review highlights the most recent advances in the literature regarding opportunities to refine our ability to detect AKI early. Importantly, this review discusses how prediction tools including novel urine and serum biomarkers, practical risk stratification tests, renal functional reserve, and electronic medical record alerts may ultimately be applied to routine clinical practice.
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Affiliation(s)
- Dana Fuhrman
- Department of Critical Care Medicine, Department of Pediatrics, Division of Nephrology, The Center for Critical Care Nephrology, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.
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Sampaio de Souza Garms D, Cardoso Eid KZ, Burdmann EA, Marçal LJ, Antonângelo L, Dos Santos A, Ponce D. The Role of Urinary Biomarkers as Diagnostic and Prognostic Predictors of Acute Kidney Injury Associated With Vancomycin. Front Pharmacol 2021; 12:705636. [PMID: 34630082 PMCID: PMC8495315 DOI: 10.3389/fphar.2021.705636] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 07/30/2021] [Indexed: 11/30/2022] Open
Abstract
Introduction: The incidence of acute kidney injury (AKI) related to vancomycin is variable, and several risk factors related to the treatment and patients may explain the nephrotoxicity. The role of urinary biomarkers in AKI related to vancomycin is unknown. Objective: The aim of this study was to evaluate the role of urinary IL-18, KIM-1, NGAL, TIMP-2, and IGFBP7 as diagnostic and prognostic predictors of AKI related to vancomycin. Methods: A prospective cohort study of patients receiving vancomycin and admitted to wards of a public university hospital from July 2019 to May 2020 was performed. We excluded patients that had AKI before starting vancomycin, hemodynamic instability, inability to collect urine, and chronic kidney disease stage 5. Results: Ninety-four patients were included, and the prevalence of AKI was 24.5%, while the general mortality was 8.7%. AKI occurred 11 ± 2 days after the first vancomycin dose. The most frequent KDIGO stage was 1 (61%). There was no difference between patients who developed and did not develop AKI due to gender, length of hospital stay, dose, and time of vancomycin use. Logistic regression identified age (OR 6.6, CI 1.16–38.22, p = 0.03), plasmatic vancomycin concentrations between 96 and 144 h (OR 1.18, CI 1.04-1.40, p = 0.04), and urinary NGAL levels between 96 and 144 h (OR 1.123, CI 1.096–1.290, p = 0.03) as predictors of AKI. The time of vancomycin use (OR 4.61, CI 1.11–22.02, p = 0.03), higher plasmatic vancomycin concentrations between 192 and 240 h (OR 1.02, CI 0.98–1.06, p = 0.26), and higher cell cycle arrest urinary biomarkers TIMP-2 multiplied by IGFBP-7 between 144 and 192 h (OR 1.33, CI 1.10–1.62, p = 0.02; OR 1.19, CI 1.09–1.39, p = 0.04, respectively) were identified as prognostic factors for non-recovery of kidney function at discharge. Conclusion: AKI related to vancomycin was frequent in patients hospitalized in wards. Age, plasmatic vancomycin concentrations, and NGAL between 96 and 144 h were identified as predictors of AKI related to vancomycin use. Plasmatic vancomycin concentrations and urinary NGAL were predictors of AKI diagnosis within the next 5 days. The urinary biomarkers of cell cycle arrest TIMP-2 and IGFBP-7 and the duration of vancomycin use were associated with non-recovery of kidney function at hospital discharge moment.
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Affiliation(s)
| | | | | | - Lia Junqueira Marçal
- Department of Internal Medicine, University of São Paulo State, São Paulo, Brazil
| | - Leila Antonângelo
- LIM 12, Nephrology Discipline of University of São Paulo, São Paulo, Brazil
| | - Adriano Dos Santos
- Clinics Hospital Pharmacy, Botucatu School of Medicine, São Paulo, Brazil
| | - Daniela Ponce
- Department of Internal Medicine, University of São Paulo State, São Paulo, Brazil
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Guo S, Bai L, Tong Y, Yu J, Zhang P, Duan X, Liu J. Contrast media exposure in the perioperative period confers no additional risk of acute kidney injury in infants and young children undergoing cardiac surgery with cardiopulmonary bypass. Pediatr Nephrol 2021; 36:2485-2491. [PMID: 33550507 DOI: 10.1007/s00467-021-04964-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 12/29/2020] [Accepted: 01/21/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Recently, there has been an interest in the temporal relationship between contrast exposure (CM) and cardiac surgery suggesting that a "double hit" on the kidney function in close succession increases the risk of acute kidney injury (AKI) after cardiac surgery. However, data from young children is limited. The purpose of this study was to retrospectively evaluate the effects of preoperative CM exposure on postoperative AKI in infant and young children patients and to further analyze the influence of exposure time interval. METHODS Patients (age ≤ 3 years) who underwent diagnostic imaging within 14 days before on-pump cardiac surgery between 1 May 2017 and 31 May 2018 in Fuwai Hospital, Beijing, were analyzed. Kidney outcome was assessed according to Kidney Disease: Improving Global Outcomes creatinine-based criteria. RESULTS One thousand four hundred pediatric patients (192 CM and 1,248 non-CM) were identified. Postoperative AKI occurred in 57 (29.7%) of the 192 patients who were exposed to CM. Following propensity score adjustment, no difference in risk for AKI was observed between the CM and non-CM groups (RR 1.142, 95% CI 0.916-1.424; P = 0.264). Multivariable logistic regression of the CM group indicated that independent predictors of postoperative AKI were lower weight, lower preoperative creatinine level, and longer CPB duration. Time interval between CM exposure and on-pump cardiac surgery was not significantly associated with increased risk of AKI (OR 0.853, 95% CI 0.265~2.747; P = 0.790). CONCLUSIONS For pediatric patients who are soon to undergo on-pump cardiac procedures, there appears to be no need to hesitate in performing the diagnostic imaging investigations requiring CM, or delay CPB after CM exposure. These patients may benefit from increased diagnostic utility without increasing their risk of postoperative AKI.
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Affiliation(s)
- Shengwen Guo
- Department of Cardiopulmonary Bypass, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Liting Bai
- Department of Cardiopulmonary Bypass, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Yuanyuan Tong
- Department of Cardiopulmonary Bypass, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Jin Yu
- Department of Cardiopulmonary Bypass, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Peiyao Zhang
- Department of Cardiopulmonary Bypass, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Xin Duan
- Department of Cardiopulmonary Bypass, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
| | - Jinping Liu
- Department of Cardiopulmonary Bypass, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
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Rosa VEE, Campos CM, Bacelar A, Abizaid AAC, Mangione JA, Lemos PA, Esteves V, Caramori P, Sampaio RO, Tarasoutchi F, Mehran R, Brito FS. Performance of Prediction Models for Contrast-Induced Acute Kidney Injury after Transcutaneous Aortic Valve Replacement. Cardiorenal Med 2021; 11:166-173. [PMID: 34261063 DOI: 10.1159/000517058] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 04/29/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Acute kidney injury (AKI) has shown to adversely affect outcomes in patients undergoing transcutaneous aortic valve replacement (TAVR), and its correct risk estimation may interfere in procedural planning and strategies. The aim of the study was to test and compare 6 scores in predicting AKI after TAVR. METHODS We tested 6 scores (the contrast material limit score, volume-to-creatinine clearance ratio, ACEF, CR4EATME3AD3, Mehran model A, and Mehran model B) in a total of 559 consecutive patients included in the Brazilian TAVR registry. RESULTS All scores had a poor accuracy and calibration to predict the occurrence of AKI grade 1 or 2. All scores improved the accuracy of AKI risk prediction when stratified for AKI grade 2/3 and AKI grade 3 for all scores. The CR4EATME3AD3 was the best predictor of AKI stage 2/3 (AUC: 0.62; OR: 1.12; 95% CI 1.01-1.26; p = 0.04) and AKI stage 3 (AUC: 0.64; OR: 1.16; 95% CI 1.02-1.32; p = 0.02). Mehran models A and B were both good models for AKI stage 3 (AUC: 0.63; OR: 1.10; 95% CI 1.01-1.22; p = 0.05; and AUC: 0.62; OR: 1.10; 95% CI 1.00-1.21; p = 0.05, respectively). CONCLUSIONS None of the current models demonstrated validity in detecting AKI when its lower grades were evaluated. CR4EATME3AD3 was the best score in predicting moderate to severe AKI after TAVR. These findings suggest that contrast-induced AKI may not be the only factor related to kidney injury after TAVR.
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Affiliation(s)
- Vitor E E Rosa
- Hospital Israelita Albert Einstein, São Paulo, Brazil, .,Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil,
| | - Carlos M Campos
- Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.,Instituto Prevent Senior, São Paulo, Brazil
| | | | | | | | - Pedro A Lemos
- Hospital Israelita Albert Einstein, São Paulo, Brazil.,Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
| | | | | | - Roney O Sampaio
- Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
| | - Flávio Tarasoutchi
- Hospital Israelita Albert Einstein, São Paulo, Brazil.,Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
| | | | - Fabio S Brito
- Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.,Hospital Sírio-Libanês, São Paulo, Brazil
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Yoshihara F, Hosoda H, Doi T, Yoshida M, Kitamura K, Yamamoto H, Asaumi Y, Ishibashi-Ueda H, Kishida M, Arisato T, Matsuo M, Miyazato M, Yasuda S. Combined evaluation of plasma B-type natriuretic peptide and urinary liver-type fatty acid-binding protein/creatinine ratio is related to worsening renal function in patients undergoing elective percutaneous coronary intervention. Clin Exp Nephrol 2021; 25:1319-1328. [PMID: 34255252 DOI: 10.1007/s10157-021-02113-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 07/09/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND There are few reports on the significance for the combined evaluation of blood humoral factors and urinary biomarkers in terms of worsening renal function (WRF) after coronary angiography (CAG)/percutaneous coronary arterial intervention (PCI). METHOD AND RESULTS Urinary liver type-fatty acid-binding protein (L-FABP), neutrophil gelatinase associated lipocalin (NGAL), and adrenomedullin (AM) were measured less than 24 h before and 3 h, 6 h, 1 day, and 2 days after CAG/PCI. WRF was defined as a > 20% decrease in the estimated GFR. WRF occurred in seven of 100 patients and the increase in L-FABP/creatinine (Cr) at 1 day after CAG/PCI was significantly higher in the WRF group than in the non-WRF group. Plasma B-type natriuretic peptide (BNP) before CAG/PCI and L-FABP/Cr at 1 day after CAG/PCI were independent predictors for WRF. The areas under the receiver-operating characteristic curves were as follows: 0.760 for BNP before CAG/PCI, 0.731 for L-FABP/Cr at 1 day after CAG/PCI, and 0.892 for BNP and L-FABP/Cr. Urinary AM levels after PCI/CAG were negatively correlated only to serum potassium levels. Gene expressions of AM and AM-receptor were detectable in renal tubule epithelial cells. AM increased intracellular second messenger levels in a dose-dependent manner. CONCLUSIONS Our results suggest that combined evaluation of plasma BNP and urinary L-FABP/Cr is useful as a predictor of renal dysfunction in CAG/PCI patients.
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Affiliation(s)
- Fumiki Yoshihara
- Division of Nephrology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan.
| | - Hiroshi Hosoda
- Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Takahito Doi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Morikatsu Yoshida
- Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmmachi, Suita, Osaka, 564-8565, Japan
| | - Kazuo Kitamura
- Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Haruko Yamamoto
- Center for Advancing Clinical and Translational Sciences, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Yasuhide Asaumi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Hatsue Ishibashi-Ueda
- Department of Pathology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Masatsugu Kishida
- Division of Nephrology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Tetsuya Arisato
- Division of Nephrology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Miki Matsuo
- Division of Nephrology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Mikiya Miyazato
- Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmmachi, Suita, Osaka, 564-8565, Japan
| | - Satoshi Yasuda
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
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Darawshi S, Yaseen H, Gorelik Y, Faor C, Szalat A, Abassi Z, Heyman SN, Khamaisi M. Biomarker evidence for distal tubular damage but cortical sparing in hospitalized diabetic patients with acute kidney injury (AKI) while on SGLT2 inhibitors. Ren Fail 2021; 42:836-844. [PMID: 32787602 PMCID: PMC7472507 DOI: 10.1080/0886022x.2020.1801466] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background Inhibitors of sodium-glucose co-transporter-2 (SGLT2i) were found to improve renal outcome in diabetic patients in large prospective randomized trials. Yet, SGLT2i may acutely reduce kidney function through volume depletion, altered glomerular hemodynamics or intensified medullary hypoxia leading to acute tubular injury (ATI). The aim or this study was to prospectively assess the pathophysiology of acute kidney injury (AKI) in patients hospitalized while on SGLT2i, differing ATI from pre-renal causes using renal biomarkers. Methods Serum and urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Ischemia Molecule (KIM)-1, markers of distal and proximal tubular injury, respectively, were determined in 46 diabetic patients who were on SGLT2i upon hospitalization with an acute illness. Results Serum and urine NGAL, but not KIM-1, were significantly increased in 21 of the patients who presented with AKI upon admission, as compared with 25 patients that maintained kidney function. Both serum and urinary NGAL correlated with the degree of impaired renal function, which in many cases was likely the result of additional acute renal perturbations, such as sepsis. Conclusions Increased urinary and serum NGAL indicates that ATI, principally affecting distal tubular segments, may develop in some of the patients hospitalized with an acute illness and AKI while on SGLT2i. It is suggested that intensified medullary hypoxia by SGLT2i might be detrimental in this injury. By contrast, concomitantly unaltered KIM-1 might reflect improved cortical oxygenation by SGLT2i, and may explain an overall reduced risk of AKI with SGLT1i in large series. The independent potential of SGLT2i to inflict medullary hypoxic damage should be explored further.
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Affiliation(s)
- Said Darawshi
- Department of Medicine D, Ruth & Bruce Rappaport Faculty of Medicine, Rambam Health Care Campus, Technion-IIT, Haifa, Israel.,Clinical Research Institute, Rambam Health Care Campus, Haifa, Israel
| | - Hiba Yaseen
- Clinical Research Institute, Rambam Health Care Campus, Haifa, Israel
| | - Yuri Gorelik
- Department of Medicine D, Ruth & Bruce Rappaport Faculty of Medicine, Rambam Health Care Campus, Technion-IIT, Haifa, Israel.,Clinical Research Institute, Rambam Health Care Campus, Haifa, Israel
| | - Caroline Faor
- Department of Medicine D, Ruth & Bruce Rappaport Faculty of Medicine, Rambam Health Care Campus, Technion-IIT, Haifa, Israel.,Clinical Research Institute, Rambam Health Care Campus, Haifa, Israel
| | - Auryan Szalat
- Department of Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Zaid Abassi
- Department of Physiology, Ruth & Bruce Rappaport Faculty of Medicine, Technion-IIT, Haifa, Israel.,Department of Laboratory Medicine, Rambam Health Care Campus, Haifa, Israel
| | - Samuel N Heyman
- Department of Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Mogher Khamaisi
- Department of Medicine D, Ruth & Bruce Rappaport Faculty of Medicine, Rambam Health Care Campus, Technion-IIT, Haifa, Israel.,Clinical Research Institute, Rambam Health Care Campus, Haifa, Israel
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Abosamak MF, Alkholy AF. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are early predictors for acute kidney injury among patients admitted to the surgical ICU. EGYPTIAN JOURNAL OF ANAESTHESIA 2021. [DOI: 10.1080/11101849.2020.1866883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
Affiliation(s)
- Mohammed F Abosamak
- Department of Anesthesia & ICU, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Adel F Alkholy
- Department of Medical Biochemistry, Faculty of Medicine, Benha University, Benha, Egypt
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Incidence, Risk Factors, the Role of Plasma NGAL and Outcome of Contrast-Induced Acute Kidney Injury in Critically Ill Children. Indian J Pediatr 2021; 88:34-40. [PMID: 32651866 DOI: 10.1007/s12098-020-03414-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 06/12/2020] [Indexed: 10/23/2022]
Abstract
OBJECTIVES To study the incidence of contrast-induced acute kidney injury (CI-AKI), evaluate its risk factors, study the role of plasma neutrophil gelatinase-associated lipocalin (NGAL) and evaluate the outcome of CI-AKI in critically ill children. METHODS In this prospective cohort study, children aged 1 mo to 12 y who underwent contrast computed tomography (CECT) for various medical indications were included. Patients without renal function test before contrast administration, children with chronic kidney disease, children admitted for less than 48 h, and those with serum bilirubin more than 5 mg per dL were excluded. Serum creatinine and estimated-Glomerular filtration rate (e-GFR) were measured at admission, immediately before, and at 6, 24, 48 h after contrast. Plasma neutrophil gelatinase-associated lipocalin (NGAL) was measured before and 6 h after contrast. The incidence of CI-AKI by p-RIFLE (Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease) criteria, its risk factors, the diagnostic role of NGAL in CI-AKI, and outcomes [30 d unfavorable outcome (death, readmission) and renal recovery] were studied. RESULTS One hundred children were enrolled. The indications for CECT were brain (58%) and respiratory pathology (20%). Incidence of CI-AKI was 35% (95% CI 26.4% to 44.8%); 71% in 'Risk,' and 29% in the 'Injury' stage. After multivariate logistic regression, age younger than 2 y was independently associated with CI-AKI. There was no significant difference in NGAL before (ROC-AUC 0.38, 95% CI 0.26 to 0.50) and 6 h after CECT scan (AUC 0.41, 95% CI 0.29 to 0.54) to predict CI-AKI. There were 7% deaths but no readmission at 30 d. Among 33 CI-AKI patients who survived, the operational definition of renal recovery was achieved in 51.5% (n = 17), complete renal recovery was achieved in 97% (n = 32), and partial renal recovery was achieved in 3% (n = 1) of patients at discharge, while none received renal supportive therapy. CONCLUSIONS The incidence of contrast-induced acute kidney injury was 35% with age younger than two year being independently associated with CI-AKI. NGAL did not predict the CI-AKI.
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Yi A, Lee CH, Yun YM, Kim H, Moon HW, Hur M. Effectiveness of Plasma and Urine Neutrophil Gelatinase-Associated Lipocalin for Predicting Acute Kidney Injury in High-Risk Patients. Ann Lab Med 2021; 41:60-67. [PMID: 32829580 PMCID: PMC7443531 DOI: 10.3343/alm.2021.41.1.60] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 02/10/2020] [Accepted: 07/29/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Neutrophil gelatinase-associated lipocalin (NGAL) is a useful biomarker for acute kidney injury (AKI) prediction. However, studies on whether using both plasma NGAL (PNGAL) and urine NGAL (UNGAL) can improve AKI prediction are limited. We investigated the best approach to predict AKI in high-risk patients when using PNGAL and UNGAL together. METHODS We enrolled 151 AKI suspected patients with one or more AKI risk factors. We assessed the diagnostic performance of PNGAL and UNGAL for predicting AKI according to chronic kidney disease (CKD) status by determining the areas under the receiver operating curve (AuROC). Independent predictors of AKI were assessed using univariate and multivariate logistic regression analyses. RESULTS In the multivariate logistic regression analysis for all patients (N=151), Model 2 and 3, including PNGAL (P=0.012) with initial serum creatinine (S-Cr), showed a better AKI prediction power (R2=0.435, both) than Model 0, including S-Cr only (R2=0.390). In the non-CKD group (N=135), the AuROC of PNGAL for AKI prediction was larger than that of UNGAL (0.79 vs 0.66, P=0.010), whereas in the CKD group (N=16), the opposite was true (0.94 vs 0.76, P=0.049). CONCLUSIONS PNGAL may serve as a useful biomarker for AKI prediction in high-risk patients. However, UNGAL predicted AKI better than PNGAL in CKD patients. Our findings provide guidance for selecting appropriate specimens for NGAL testing according to the presence of CKD in AKI high-risk patients.
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Affiliation(s)
- Ahram Yi
- Department of Laboratory Medicine, Green Cross Laboratories, Yongin,
Korea
| | - Chang-Hoon Lee
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul,
Korea
| | - Yeo-Min Yun
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul,
Korea
| | - Hanah Kim
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul,
Korea
| | - Hee-Won Moon
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul,
Korea
| | - Mina Hur
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul,
Korea
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Horváth J, Wullt B, Naber KG, Köves B. Biomarkers in urinary tract infections - which ones are suitable for diagnostics and follow-up? GMS INFECTIOUS DISEASES 2020; 8:Doc24. [PMID: 33299741 PMCID: PMC7705555 DOI: 10.3205/id000068] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Introduction: Urinary tract infections (UTIs) are one of the most common infections worldwide. Under special circumstances, clinicians must rely on laboratory findings, which might have a weak predicting value, misguiding the practitioners and leading to incorrect diagnosis and overuse of antibiotics. Therefore, there is an urgent need for reliable biomarkers in UTIs. Methods: We performed a literature search for biomarkers used in UTIs from January 1999 until May 2020. We used "urinary tract infection" and "biomarker" as the main key words in the PubMed, Medline and Cochrane databases. After peer review, we excluded the duplicates and identified the suitable articles, from which we collected the data and divided the available biomarkers into 5 groups: i) conventional markers; ii) promising, thoroughly studied biomarkers; iii) promising biomarkers that need further studies; iv) biomarkers of unknown significance; v) controversial, not useful markers. Results: We found 131 articles, mostly from the paediatric population. Neutrophil gelatinase-associated lipocalin (NGAL) and interleukins (IL) have a leading role in diagnosing and differentiating UTIs based on a lot of observational, comparative trials. Heparin Binding Protein (HBP), Lactoferrin (LF), Heat-Shock Protein-70 (HSP-70), Human Defensin-5 (HD-5), Lipopolysaccharide Binding Protein (LBP) and mass spectrometry studies are promising, but confirming data are lacking. The measurable components of the innate immune system and local host cell response could be appropriate biomarkers, but their significance is currently unknown. Conclusions: Conventional biomarkers for UTIs have low specificity. The use of urinary NGAL and interleukins could improve the sensitivity and specificity of laboratory diagnosis of UTIs.
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Affiliation(s)
- József Horváth
- BKMK SZTE ÁOK Okt. Kh. Urológiai Osztálya, Kecskemét, Hungary
| | - Björn Wullt
- Division of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden
| | - Kurt G. Naber
- Department of Urology, Technical University of Munich, Munich, Germany
| | - Béla Köves
- Jahn Ferenc Dél-pesti Kórház és Rendelőintézet, Budapest, Hungary
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Choi YH, Lee DH, Lee JH. The title: serum neutrophil Gelatinase-associated Lipocalin at 3 hours after return of spontaneous circulation in patients with cardiac arrest and therapeutic hypothermia: early predictor of acute kidney injury. BMC Nephrol 2020; 21:389. [PMID: 32894077 PMCID: PMC7487645 DOI: 10.1186/s12882-020-02054-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 09/02/2020] [Indexed: 03/20/2023] Open
Abstract
Background Serum neutrophil gelatinase-associated lipocalin (NGAL) could be used as a predictive marker of acute kidney injury (AKI) in patients with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) who are managed with targeted temperature management (TTM). However, the NGAL measurement timepoints vary from immediately after ROSC to several days later. The primary objective of this study was to determine an association between AKI and NGAL, both immediately (ROSC-NGAL) and 3 h after ROSC (3 h-NGAL), in OHCA patients with TTM. The secondary objective was to ascertain the association between NGAL levels in the early post-ROSC phase and the neurologic outcomes at discharge. Methods This prospective observational study was conducted between January 2016 and December 2018 and enrolled adult OHCA patients (≥18 years) with TTM after ROSC. The serum NGAL level was measured both immediately and 3 h after ROSC. Univariate and multivariate analyses were performed to identify the associations between AKI, poor neurologic outcome, and NGAL. Results Among 861 OHCA patients, 89 patients were enrolled. AKI occurred in 48 (55.1%) patients. On multivariate logistic regression analysis, 3 h-NGAL was significantly associated with AKI (odds ratio [OR] 1.022; 95% confidence interval [CI] 1.009–1.035; p = 0.001). The area under the receiver operating characteristic curve of 3 h-NGAL for AKI was 0.910 (95% CI 0.830–0.960), and a cut-off value of 178 ng/mL was identified. Both ROSC-NGAL and 3 h-NGAL were not significantly associated with poor neurologic outcome on multivariate logistic regression analysis (ROSC-NGAL; OR 1.017; 95% CI 0.998–1.036; p = 0.084, 3 h-NGAL; OR 0.997; 95% CI 0.992–1.001; p = 0.113). Conclusions The serum NGAL concentration measured 3 h after ROSC is an excellent early predictive marker for AKI in OHCA patients treated with TTM. Future research is needed to identify the optimal measurement timepoint to establish NGAL as a predictor of neurologic outcome and to validate the findings of this research.
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Affiliation(s)
- Yoon Hee Choi
- Department of Emergency Medicine, College of Medicine, Ewha Womans University Mokdong Hospital, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 07985, South Korea
| | - Dong Hoon Lee
- Department of Emergency Medicine, Chung-Ang University, College of Medicine, Seoul, South Korea
| | - Jae Hee Lee
- Department of Emergency Medicine, College of Medicine, Ewha Womans University Mokdong Hospital, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 07985, South Korea.
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Cystatin C, Neutrophil Gelatinase-associated Lipocalin, and Lysozyme C: Urinary Biomarkers for Detection of Early Kidney Dysfunction in Children With Urolithiasis. Urology 2020; 143:221-226. [DOI: 10.1016/j.urology.2020.05.050] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 05/18/2020] [Accepted: 05/25/2020] [Indexed: 01/04/2023]
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Heyman SN, Khamaisi M, Zorbavel D, Rosen S, Abassi Z. Role of Hypoxia in Renal Failure Caused by Nephrotoxins and Hypertonic Solutions. Semin Nephrol 2020; 39:530-542. [PMID: 31836036 DOI: 10.1016/j.semnephrol.2019.10.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hypoxia plays a role in the pathogenesis of acute kidney injury under diverse clinical settings, including nephrotoxicity. Although some nephrotoxins exert direct renal parenchymal injury, likely with consequent altered oxygenation, others primarily reduce renal parenchymal oxygenation, leading to hypoxic tubular damage. As outlined in this review, nephrotoxin-related renal hypoxia may result from an altered renal oxygen supply (cyclosporine), enhanced oxygen consumption for tubular transport (agents inducing osmotic diuresis), or their combination (nonsteroidal anti-inflammatory drugs, radiocontrast agents, and others). Most agents causing hypoxic renal injury further supress physiologic low medullary Po2, in which a limited regional blood supply barely matches the intense regional tubular transport and oxygen consumption. The medullary tubular transport and blood supply are finely matched, securing oxygen sufficiency. Predisposition to hypoxia-mediated nephrotoxicity by medical conditions, such as chronic kidney disease or diabetes, may be explained by malfunctioning of control systems that normally maintain medullary oxygenation. However, this propensity may be diminished by hypoxia-mediated adaptive responses governed by hypoxia-inducible factors. Recent reports have suggested that inhibitors of sodium-glucose cotransporters and the administration of hypertonic saline may be added to the growing list of common therapeutic interventions that intensify medullary hypoxia, and potentially could lead to hypoxic acute kidney injury.
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Affiliation(s)
- Samuel N Heyman
- Department of Medicine, Hadassah Hebrew University Hospital, Mt. Scopus, Jerusalem, Israel.
| | - Mogher Khamaisi
- Department of Medicine D, Rambam Health Care Campus, Haifa, Israel; Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa, Israel
| | - Danny Zorbavel
- Department of Medicine D, Rambam Health Care Campus, Haifa, Israel
| | - Seymour Rosen
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA; Department of Pathology, Harvard Medical School, Boston, MA
| | - Zaid Abassi
- Department of Physiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel; Department of Laboratory Medicine, Rambam Health Care Campus, Haifa, Israel
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Ostovar T, Rezaei H, Zavar Reza J. Assessment of the Diagnostic Validities of Serum NGAL, KIM-1, and L-FABP in Patients With Chronic Kidney Disease. INTERNATIONAL JOURNAL OF BASIC SCIENCE IN MEDICINE 2020. [DOI: 10.34172/ijbsm.2020.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Introduction: Chronic kidney disease (CKD) is one of the most threatening and important disorders worldwide in both industrial and developing nations. In addition, neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) are three factors suggested as diagnostic and prognostic biomarkers in CKDs. Considering the lack of enough efficiency of the creatinine in the prognosis of the CKD, the present study aimed to assess the relationship between these three factors and CKD occurrence and determine if they could be considered valid biomarkers in this regard. Materials and Methods: The present case-control study was designed enrolling 42 patients with confirmed CKD referring to the Imam Khomeini hospital of Kangan. The participants were 42 years old and gender-matched healthy counterparts. Blood samples were obtained, and then NGAL, KIM-1, and L-FABP were determined by the enzyme-linked immunosorbent assay using commercial kits (Bioassay Technology Laboratory). Finally, the serum creatinine was detected by applying Jaffe’s method. Results: Based on the results, significant differences were found in the serum levels of all four factors between CKD patients and the control group. More precisely, the serum levels of NGAL (P < 0.0001, specificity: 87.6%, sensitivity: 79.3%, and the area under the curve, AUC: 0.89), L-FABP (P < 0.0001, specificity: 83.3%, sensitivity: 78.3%, and AUC: 0.86), KIM-1 (P < 0.0001, specificity: 85.7%, sensitivity: 78.6%, and AUC: 0.88), and creatinine (P < 0.0001) were significantly higher in individuals with CKDs in comparison with controls. Eventually, the serum levels of NGAL, L-FABP, and KIM-1 were significantly correlated with each other in both patient and control groups (P < 0.0001). Conclusion: In general, NGAL, L-FABP, KIM-1, and creatinine could be used as independent biomarkers for the diagnosis of CKD. Moreover, the measurement of NGAL, L-FABP, and KIM-1 altogether could be a valid assessment for the diagnosis of CKD.
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Affiliation(s)
- Tahmineh Ostovar
- International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hosein Rezaei
- International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Javad Zavar Reza
- Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Reduced Albuminuria and Potassemia Indicate Early Renal Repair Processes after Resynchronization Therapy in Cardiorenal Syndrome Type 2. Cardiol Res Pract 2020; 2020:2727108. [PMID: 32274209 PMCID: PMC7115056 DOI: 10.1155/2020/2727108] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Revised: 01/19/2020] [Accepted: 02/12/2020] [Indexed: 12/20/2022] Open
Abstract
Background Patients with chronic cardiorenal syndrome type 2 (T2-CRS) who qualify for resynchronization therapy (CRT) are exposed perioperatively to potentially nephrotoxic factors including contrast agents and blood loss. Methods The objective of this prospective interventional study was to assess the effects of CRT on renal function in patients with T2-CRS within the first 48 hours following implantation. Initially, 76 patients (15% female; aged 69 ± 9.56 years) with heart failure (New York Heart Association classes II–IV), ejection fraction ≤ 35%, and QRS > 130 ms were included in the study. During CRT implantation, a nonionic contrast agent (72.2 ± 44.9 mL) was administered. Prior to and 48 hours following implantation, renal function was evaluated using the following serum biomarkers: creatinine (sCr), estimated glomerular filtration rate (using the Chronic Kidney Disease Epidemiology Collaboration equation [eGFRCKD-EPI]), and the electrolyte and urine biomarkers albumin (uAlb), albumin/creatinine ratio (UACR), and neutrophil gelatinase-associated lipocalin (uNGAL). Results Before CRT, patients classified as NYHA class III or IV had higher uNGAL levels in comparison to uNGAL levels after CRT (43.63 ± 60.02 versus 16.63 ± 18.19; p=0.041). After CRT implantation, uAlb, UACR, and potassium levels were reduced (p < 0.05), and uNGAL, sCr, and eGFRCKD-EPI were unchanged. The contrast medium volume did not correlate with the test biomarkers (p > 0.05). Conclusions In patients with T2-CRS, uNGAL is a biomarker of kidney injury that correlates with the NYHA classes. A stable uNGAL value before and after CRT implantation confirms the lack of risk of contrast-induced nephropathy. Reduced albuminuria and blood potassium are biomarkers of improving T2-CRS in the early post-CRT period.
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Abstract
Decades of pre-clinical research have revealed biologic pathways that have suggested potential therapies for acute kidney injury (AKI) in experimental models. However, translating these to human AKI has largely yielded disappointing results. Fortunately, recent discoveries in AKI molecular mechanisms are providing new opportunities for early detection and novel interventions. This review identifies technologies that are revealing the exceptionally complex nature of the normal kidney, the remarkable heterogeneity of the AKI syndrome, and the myriad responses of the kidney to AKI. Based on the current state of the art, novel approaches to improve the bench-to-bedside translation of novel discoveries are proposed. These strategies include the use of unbiased approaches to improve our understanding of human AKI, establishment of irrefutable biologic plausibility for proposed biomarkers and therapies, identification of patients at risk for AKI pre-injury using clinical scores and non-invasive biomarkers, initiation of safe, and effective preventive interventions of pre-injury in susceptible patients, identification of patients who may develop AKI post-injury using electronic triggers, clinical scores, and novel biomarkers, employment of sequential biomarkers to initiate appropriate therapies based on knowledge of the underlying pathophysiology, use of new biomarkers as criteria for enrollment in randomized clinical trials, assessing efficacy, and empowering the drug development process, and early initiation of anti-fibrotic therapies. These strategies are immediately actionable and hold tremendous promise for effective bench-to-bedside translation of novel discoveries that will change the current dismal prognosis of human AKI.
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Affiliation(s)
- Prasad Devarajan
- Department of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States
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Kim H, Jo K. Laboratory Predictors of Contrast-Induced Nephropathy After Neurointervention: A Prospective 3-Year Observational Study. World Neurosurg 2019; 135:e77-e82. [PMID: 31698123 DOI: 10.1016/j.wneu.2019.10.166] [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: 07/22/2019] [Revised: 10/23/2019] [Accepted: 10/24/2019] [Indexed: 10/25/2022]
Abstract
OBJECTIVE The purpose of this study was to assess the natural course of contrast-induced nephropathy (CIN) and to determine the predictive abilities of preprocedural high-sensitivity C-reactive protein (hs-CRP) and urine neutrophil gelatinase-associated lipocalin for CIN after neurointervention procedures. METHODS We prospectively enrolled 176 patients who underwent an elective neurointervention procedure (diagnostic angiography or endovascular surgery). CIN was defined as an increase in serum creatinine of more than 0.5 mg/dL or an increase of at least 25% from the baseline value within 48 hours of contrast media exposure. The predictive value of hs-CRP and serial urine NGAL (baseline, 6, 24, and 48 hours) for the risk of CIN was assessed using multivariate logistic regression. RESULTS CIN occurred in 17 patients (9.46%). Multivariate analysis revealed that the CIN incidence was significantly associated with high baseline hs-CRP. All patients with CIN had creatinine return to baseline levels within 7 days. No patients required dialysis or suffered permanent sequelae as a result of a creatinine increase. During the 3-year follow-up period, no cerebro- or cardiovascular events occurred in the CIN group. However, 3 patients in the non-CIN group suffered a vascular event. One was a myocardial infarction, and 2 were ischemic strokes. CONCLUSIONS The incidence of CIN after neurointervention procedures was relatively high (9.46%). The natural course of CIN was favorable, however, and did not affect cerebrovascular events. Additionally, patients with CIN typically recovered with supportive care within 7 days. Elevated preprocedural hs-CRP levels (>5 mg/dL) were a significant and independent predictor of CIN after neurointervention procedures.
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Affiliation(s)
- Hoon Kim
- Department of Neurosurgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - KwangWook Jo
- Department of Neurosurgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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Ratnayake I, Mohamed F, Buckley NA, Gawarammana IB, Dissanayake DM, Chathuranga U, Munasinghe M, Maduwage K, Jayamanne S, Endre ZH, Isbister GK. Early identification of acute kidney injury in Russell's viper (Daboia russelii) envenoming using renal biomarkers. PLoS Negl Trop Dis 2019; 13:e0007486. [PMID: 31260445 PMCID: PMC6625728 DOI: 10.1371/journal.pntd.0007486] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 07/12/2019] [Accepted: 05/23/2019] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is a major complication of snake envenoming, but early diagnosis remains problematic. We aimed to investigate the time course of novel renal biomarkers in AKI following Russell's viper (Daboia russelii) bites. METHODOLOGY/PRINCIPAL FINDINGS We recruited a cohort of patients with definite Russell's viper envenoming and collected serial blood and urine samples on admission (<4h post-bite), 4-8h, 8-16h, 16-24h, 1 month and 3 months post-bite. AKI stage (1-3) was defined using the Acute Kidney Injury Network criteria. AKI stages (1-3) were defined by the Acute Kidney Injury Network (AKIN) criteria. There were 65 Russell's viper envenomings and 49 developed AKI: 24 AKIN stage 1, 13 stage 2 and 12 stage 3. There was a significant correlation between venom concentrations and AKI stage (p = 0.007), and between AKI stage and six peak biomarker concentrations. Although most biomarker concentrations were elevated within 8h, no biomarker performed well in diagnosing AKI <4h post-bite. Three biomarkers were superior to serum creatinine (sCr) in predicting AKI (stage 2/3) 4-8h post-bite: serum cystatin C (sCysC) with an area under the receiver operating curve (AUC-ROC), 0.78 (95%CI:0.64-0.93), urine neutrophil gelatinase-associated lipocalin (uNGAL), 0.74 (95%CI:0.59-0.87) and urine clusterin (uClu), 0.81 (95%CI:0.69-0.93). No biomarker was better than sCr after 8h. Six other urine biomarkers urine albumin, urine beta2-microglobulin, urine kidney injury molecule-1, urine cystatin C, urine trefoil factor-3 and urine osteopontin either had minimal elevation, and/or minimal prediction for AKI stage 2/3 (AUC-ROC<0.7). CONCLUSIONS/SIGNIFICANCE AKI was common and sometimes severe following Russell's viper bites. Three biomarkers uClu, uNGAL and sCysC, appeared to become abnormal in AKI earlier than sCr, and may be useful in early identification of envenoming.
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Affiliation(s)
- Indira Ratnayake
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Fahim Mohamed
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
- TACT, Department of Pharmacology, Sydney Medical School, University of Sydney, Sydney, Australia
- Department of Pharmacy, Faculty of Allied Health Science, University of Peradeniya, Peradeniya, Sri Lanka
- Department of Nephrology, Prince of Wales Hospital and Clinical School, University of New South Wales, Sydney, Australia
| | - Nicholas A. Buckley
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
- TACT, Department of Pharmacology, Sydney Medical School, University of Sydney, Sydney, Australia
| | - Indika B. Gawarammana
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
- Department of Medicine, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Dhammika M. Dissanayake
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
- Department of Pathology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Umesh Chathuranga
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Mahesh Munasinghe
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Kalana Maduwage
- Department of Biochemistry, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Shaluka Jayamanne
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Zoltan H. Endre
- Department of Nephrology, Prince of Wales Hospital and Clinical School, University of New South Wales, Sydney, Australia
| | - Geoffrey K. Isbister
- South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
- Clinical Toxicology Research Group, University of Newcastle, Newcastle, NSW, Australia
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Neutrophil Gelatinase-Associated Lipocalin Is Not Associated with Tacrolimus-Induced Acute Kidney Injury in Liver Transplant Patients Who Received Mycophenolate Mofetil with Delayed Introduction of Tacrolimus. Int J Mol Sci 2019; 20:ijms20123103. [PMID: 31242630 PMCID: PMC6627315 DOI: 10.3390/ijms20123103] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 06/22/2019] [Accepted: 06/23/2019] [Indexed: 01/07/2023] Open
Abstract
Tacrolimus is widely used as an immunosuppressant in liver transplantation, and tacrolimus-induced acute kidney injury (AKI) is a serious complication. The urinary neutrophil gelatinase-associated lipocalin (NGAL) level has been linked to tacrolimus-induced AKI in patients starting tacrolimus treatment the morning after liver transplantation. Here we tested this association using a different immunosuppression protocol: Mycophenolate mofetil administration beginning on Postoperative Day 1 and tacrolimus administration beginning on Postoperative Day 2 or 3. Urine samples were collected from 26 living donor liver transplant recipients before (Postoperative Day 1) and after (Postoperative Day 7 or 14) tacrolimus administration. NGAL levels were measured via enzyme-linked immunosorbent assays, as were those of three additional urinary biomarkers for kidney diseases: Monocyte chemotactic protein-1 (MCP-1), liver-type fatty acid-binding protein (L-FABP), and human epididymis secretory protein 4 (HE4). HE4 levels after tacrolimus administration were significantly higher in patients who developed AKI (n = 6) than in those who did not (n = 20), whereas NGAL, MCP-1, and L-FABP levels did not differ significantly before or after tacrolimus administration. These findings indicate that NGAL may not be a universal biomarker of AKI in tacrolimus-treated liver transplant recipients. To reduce the likelihood of tacrolimus-induced AKI, our immunosuppression protocol is recommended.
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Does Whole-Blood Neutrophil Gelatinase-Associated Lipocalin Stratify Acute Kidney Injury in Critically Ill Patients? DISEASE MARKERS 2019; 2019:8480925. [PMID: 31191757 PMCID: PMC6525902 DOI: 10.1155/2019/8480925] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 02/11/2019] [Accepted: 03/03/2019] [Indexed: 01/03/2023]
Abstract
Purpose To analyse the capacity of whole-blood NGAL (wbNGAL) to stratify AKI in critically ill patients with and without sepsis. Methods Whole-blood NGAL was measured with a point-of-care device at admission and 48 hours later in patients admitted to a general ICU. Patients were classified by the AKIN and KDIGO classifications at admission and 24 and 48 hours. We performed an ROC curve analysis. wbNGAL values at admission were compared in patients with sepsis and septic shock. Results The study included 100 consecutively admitted patients (40 female) with mean age 59.1 ± 17.8 years. Thirty-three patients presented AKI at admission, and 10 more developed it in the next 48 h. Eighteen patients had AKI stage 3, 14 of them at admission. Nine patients required renal replacement therapy. According to KDIGO at admission, wbNGAL values were 78 μg/L (60-187) in stage 0 (n = 67), 263 μg/L (89-314) in stage 1 (n = 8), 484 μg/L (333-708) in stage 2 (n = 11), and 623 μg/L (231-911) in stage 3 (n = 14), p = 0.0001 for trend. Ten patients did not complete 48 hours of study: 6 of 10 were discharged (initial wbNGAL 130 μg/L (60-514)) and 4 died (773 μg/L (311-1010)). The AUROC curve of wbNGAL to predict AKI was 0.838 (95% confidence interval 0.76-0.92, p = 0.0001), with optimal cut-off value of 178 μg/L (sensitivity 76.7%, specificity 78.9%, p < 0.0001). At admission, twenty-nine patients had sepsis, of whom 20 were in septic shock. wbNGAL concentrations were 81 μg/L (60-187) in patients without sepsis, 481 (247-687) in those with sepsis, and 623.5 μg/L (361-798) in the subgroup of septic shock (p < 0.0001). Conclusions Whole-blood NGAL concentration at ICU admission was a good stratifier of AKI in critically ill patients. However, wbNGAL concentrations were higher in septic patients irrespective of AKI occurrence.
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YETER HH, YILDIRIM T, EYÜPOĞLU D, PAŞAYEV T, ASLAN A, ÇETİK S, AKÇAY Ö, TOPELİ A, ARICI M. Mild to moderate proteinuria is a heralding sign for acute kidney injury and mortality for intensive care unit patients. Turk J Med Sci 2019; 49:543-550. [PMID: 30997790 PMCID: PMC7018325 DOI: 10.3906/sag-1802-183] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background/aim Lack of early predictors of acute kidney injury is currently delaying timely diagnosis.This study was done to evaluate the relationship between mild to moderate proteinuria and incidence of acute kidney injury (AKI) and 28-day mortality in intensive care unit (ICU) patients. Materials and methods This observational, retrospective study was conducted in the internal medicine ICU. A total of 796 patients were screened and 525 patients were used for this analysis. Proteinuria was measured by urine dipstick test. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Results Patients with dipstick urine protein positivity on admission had higher proportion of AKI and 28-day mortality compared to dipstick urine protein negative group [164 (59.6%) vs. 111 (44.4%) and 101 (36.7%) vs. 54 (21.6%), P = 0.01 and P < 0.01, respectively]. Urine dipstick protein positivity was also a significant predictor of 28-day mortality in patients with GFR > 60 mL/min (hazard ratio: 1.988, 95% confidence interval 1.380–2.862). Conclusion Proteinuria before ICU admission is a risk factor for development of AKI within seven days of ICU stay and also is a risk factor for 28-day mortality, even in patients with GFR > 60 mL/min.
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Affiliation(s)
- Hasan H. YETER
- Department of Nephrology, Faculty of Medicine, Gazi University, AnkaraTurkey
| | - Tolga YILDIRIM
- Department of Nephrology, Faculty of Medicine, Hacettepe University, AnkaraTurkey
| | - Damla EYÜPOĞLU
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, AnkaraTurkey
| | - Tural PAŞAYEV
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, AnkaraTurkey
| | - Abdullah ASLAN
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, AnkaraTurkey
| | - Sıla ÇETİK
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, AnkaraTurkey
| | - Ömer AKÇAY
- Department of Internal Medicine, Zekai Tahiri Burak Hospital, AnkaraTurkey
| | - Arzu TOPELİ
- Intensive Care Unit, Faculty of Medicine, Hacettepe University, AnkaraTurkey
| | - Mustafa ARICI
- Department of Nephrology, Faculty of Medicine, Hacettepe University, AnkaraTurkey
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Hall PS, Mitchell ED, Smith AF, Cairns DA, Messenger M, Hutchinson M, Wright J, Vinall-Collier K, Corps C, Hamilton P, Meads D, Lewington A. The future for diagnostic tests of acute kidney injury in critical care: evidence synthesis, care pathway analysis and research prioritisation. Health Technol Assess 2019; 22:1-274. [PMID: 29862965 DOI: 10.3310/hta22320] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is highly prevalent in hospital inpatient populations, leading to significant mortality and morbidity, reduced quality of life and high short- and long-term health-care costs for the NHS. New diagnostic tests may offer an earlier diagnosis or improved care, but evidence of benefit to patients and of value to the NHS is required before national adoption. OBJECTIVES To evaluate the potential for AKI in vitro diagnostic tests to enhance the NHS care of patients admitted to the intensive care unit (ICU) and identify an efficient supporting research strategy. DATA SOURCES We searched ClinicalTrials.gov, The Cochrane Library databases, Embase, Health Management Information Consortium, International Clinical Trials Registry Platform, MEDLINE, metaRegister of Current Controlled Trials, PubMed and Web of Science databases from their inception dates until September 2014 (review 1), November 2015 (review 2) and July 2015 (economic model). Details of databases used for each review and coverage dates are listed in the main report. REVIEW METHODS The AKI-Diagnostics project included horizon scanning, systematic reviewing, meta-analysis of sensitivity and specificity, appraisal of analytical validity, care pathway analysis, model-based lifetime economic evaluation from a UK NHS perspective and value of information (VOI) analysis. RESULTS The horizon-scanning search identified 152 potential tests and biomarkers. Three tests, Nephrocheck® (Astute Medical, Inc., San Diego, CA, USA), NGAL and cystatin C, were subjected to detailed review. The meta-analysis was limited by variable reporting standards, study quality and heterogeneity, but sensitivity was between 0.54 and 0.92 and specificity was between 0.49 and 0.95 depending on the test. A bespoke critical appraisal framework demonstrated that analytical validity was also poorly reported in many instances. In the economic model the incremental cost-effectiveness ratios ranged from £11,476 to £19,324 per quality-adjusted life-year (QALY), with a probability of cost-effectiveness between 48% and 54% when tests were compared with current standard care. LIMITATIONS The major limitation in the evidence on tests was the heterogeneity between studies in the definitions of AKI and the timing of testing. CONCLUSIONS Diagnostic tests for AKI in the ICU offer the potential to improve patient care and add value to the NHS, but cost-effectiveness remains highly uncertain. Further research should focus on the mechanisms by which a new test might change current care processes in the ICU and the subsequent cost and QALY implications. The VOI analysis suggested that further observational research to better define the prevalence of AKI developing in the ICU would be worthwhile. A formal randomised controlled trial of biomarker use linked to a standardised AKI care pathway is necessary to provide definitive evidence on whether or not adoption of tests by the NHS would be of value. STUDY REGISTRATION The systematic review within this study is registered as PROSPERO CRD42014013919. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Peter S Hall
- Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, UK
| | | | - Alison F Smith
- Academy of Primary Care, Hull York Medical School, Hull, UK.,National Institute for Health Research (NIHR) Diagnostic Evidence Co-operative Leeds, Leeds, UK
| | - David A Cairns
- Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Michael Messenger
- National Institute for Health Research (NIHR) Diagnostic Evidence Co-operative Leeds, Leeds, UK
| | | | - Judy Wright
- Academy of Primary Care, Hull York Medical School, Hull, UK
| | | | | | - Patrick Hamilton
- Manchester Institute of Nephrology and Transplantation, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - David Meads
- Academy of Primary Care, Hull York Medical School, Hull, UK
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Benoit SW, Dixon BP, Goldstein SL, Bennett MR, Lane A, Lounder DT, Rotz SJ, Gloude NJ, Lake KE, Litts B, Davies SM. A novel strategy for identifying early acute kidney injury in pediatric hematopoietic stem cell transplantation. Bone Marrow Transplant 2019; 54:1453-1461. [PMID: 30700793 DOI: 10.1038/s41409-018-0428-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 11/07/2018] [Accepted: 12/09/2018] [Indexed: 01/09/2023]
Abstract
Acute kidney injury (AKI) is a common complication in pediatric hematopoietic stem cell transplantation (HSCT). Serum creatinine is an imprecise biomarker of AKI. We hypothesized that combining creatinine with serum cystatin C (cysC) and urinary neutrophil gelatinase-associated lipocalin (NGAL) more effectively characterizes AKI during the first 28 days of HSCT and better identifies patients at risk of adverse outcomes than creatinine alone. We prospectively assessed the type and severity of AKI in 80 consecutive allogeneic HSCT patients using weekly creatinine, cysC, and NGAL. We combined the biomarkers to define 7 Composite Types of AKI, including All Positive AKI (simultaneously detected creatinine, cysC, and NGAL AKI). Outcomes included renal replacement therapy and transplant-related mortality. In all, 75% of patients had AKI by at least one measure; 33% developed >1 type of AKI. Mild AKI often preceded Severe AKI. Patients with creatinine or NGAL AKI that were Severe or Repeated tended to have worse outcomes. The five patients with All Positive AKI had the highest rates of morbidity and mortality. AKI evaluation with creatinine, cysC, and NGAL provides a comprehensive profile of early AKI and narrowly identifies patients at highest risk of adverse outcomes, providing opportunities for early, impactful intervention.
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Affiliation(s)
- Stefanie W Benoit
- Division of Nephrology & Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
| | - Bradley P Dixon
- Kidney Center at Children's Hospital Colorado Medical Center, Aurora, CO, USA.,Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
| | - Stuart L Goldstein
- Division of Nephrology & Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,University of Cincinnati College of Medicine, Cincinnati, OH, USA.,Center for Acute Care Nephrology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Michael R Bennett
- Division of Nephrology & Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Adam Lane
- University of Cincinnati College of Medicine, Cincinnati, OH, USA.,Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | | | - Seth J Rotz
- Department of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation, Cleveland Clinic Foundation, Cleveland, OH, USA.,Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
| | - Nicholas J Gloude
- University of California San Diego, Rady Children's Hospital, San Diego, CA, USA
| | - Kelly E Lake
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Bridget Litts
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Stella M Davies
- University of Cincinnati College of Medicine, Cincinnati, OH, USA.,Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
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50
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Chen YH, Fu YC, Wu MJ. Does Resveratrol Play a Role in Decreasing the Inflammation Associated with Contrast Induced Nephropathy in Rat Model? J Clin Med 2019; 8:jcm8020147. [PMID: 30691208 PMCID: PMC6406726 DOI: 10.3390/jcm8020147] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Revised: 01/13/2019] [Accepted: 01/24/2019] [Indexed: 01/14/2023] Open
Abstract
Contrast is widely used in invasive image examinations such as computed tomography (CT) and angiography; however, the risk of contrast-induced nephropathy (CIN) is high. The aim of this study was to investigate the protective effect of resveratrol in a rat model of CIN. Sprague-Dawley rats were divided into four groups: the control group (0.9% saline infusion only); resveratrol group (RSV, resveratrol, 30 mg/kg); contrast media group (CIN); and resveratrol + contrast media group (RCIN, resveratrol 30 mg/kg 60 min before CIN). CIN was induced via an intravenous injection of a single dose of indomethacin (10 mg/kg), one dose of N-nitro-L-arginine methyl ester (10 mg/kg), and a single dose of contrast medium iopromide (2 g/kg). Blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) were higher in the CIN group compared to the other groups. Histopathological tubule injury scores were also higher in the CIN group compared to the other groups (p < 0.01). NLPR3 in kidney tissue were higher in the CIN group compared to the other groups; however, these results were improved by resveratrol in the RCIN group compared with the CIN group. The expressions of IL-1β and the percentage of apoptotic cells were higher in the CIN group than in the control and RSV groups, but they were lower in the RCIN group than in the CIN group. The expression of cleaved caspase-3 was higher in the CIN group than in the control and RSV groups, but lower in the RCIN group than in the CIN group. Resveratrol treatment attenuated both injury processes and apoptosis and inhibited the inflammasome pathway in this rat CIN model.
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Affiliation(s)
- Yi-Hsin Chen
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan.
- Department of Nephrology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427, Taiwan.
- School of Medicine, Tzu Chi University, Hualien 907, Taiwan.
| | - Yun-Ching Fu
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan.
- School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan.
- Section of Pediatric Cardiology, Department of Pediatrics, Taichung Veterans General Hospital, Taichung 407, Taiwan.
| | - Ming-Ju Wu
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan.
- School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan.
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan.
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
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