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Tang L, Li Y, Zhang J, Zhang F, Tang Q, Zhang X, Wang S, Zhang Y, Ma S, Liu R, Chen L, Ma J, Zou X, Yao T, Tang R, Zhou H, Wu L, Yi Y, Zeng Y, Wang D, Zhang L. Machine learning model to predict sepsis in ICU patients with intracerebral hemorrhage. Sci Rep 2025; 15:16326. [PMID: 40348861 PMCID: PMC12065919 DOI: 10.1038/s41598-025-99431-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 04/21/2025] [Indexed: 05/14/2025] Open
Abstract
Patients with intracerebral hemorrhage (ICH) are highly susceptible to sepsis. This study evaluates the efficacy of machine learning (ML) models in predicting sepsis risk in intensive care units (ICUs) patients with ICH. We conducted a retrospective analysis on ICH patients using the MIMIC-IV database, randomly dividing them into training and validation cohorts. We identified sepsis prognostic factors using Least Absolute Shrinkage and Selection Operator (LASSO) and backward stepwise logistic regression. Several machine learning algorithms were developed and assessed for predictive accuracy, with external validation performed using the eICU Collaborative Research Database (eICU-CRD). We analyzed 2,214 patients, including 1,550 in the training set, 664 in the validation set, and 513 for external validation using the eICU-CRD. The Random Forest (RF) model outperformed others, achieving Area Under the Curves (AUCs) of 0.912 in training, 0.832 in internal validation, and 0.798 in external validation. Neural Network and Logistic Regression models recorded training AUCs of 0.840 and 0.804, respectively. ML models, especially the RF model, effectively predict sepsis in ICU patients with ICH, enabling early identification and management of high-risk cases.
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Affiliation(s)
- Lei Tang
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Ye Li
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Ji Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
| | - Feng Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
- Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Qiaoling Tang
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Xiangbin Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Sai Wang
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Yupeng Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Siyuan Ma
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Ran Liu
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Lei Chen
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Junyi Ma
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Xuelun Zou
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Tianxing Yao
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Rongmei Tang
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Huifang Zhou
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Lianxu Wu
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Yexiang Yi
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
| | - Yi Zeng
- Department of Geriatrics, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Duolao Wang
- Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
| | - Le Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Jiangxi, Nanchang, 330006, Jiangxi, China.
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Changsha, Hunan, China.
- Brain Health Center of Hunan Province, Changsha, Hunan, China.
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
- FuRong Laboratory, Changsha, 410078, Hunan, China.
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Marchenko TV, Nikoda VV, Lishova EA, Goncharova AV, Mayachkin RB. [Renal replacement therapy after elective surgical procedures]. Khirurgiia (Mosk) 2019:62-68. [PMID: 31626241 DOI: 10.17116/hirurgia201910162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Acute kidney injury (AKI) is not a rare postoperative complication in surgical patients. AKI dramatically affects patient's condition, increases hospital-stay and risk of lethal outcome. Moreover, AKI may be followed by deterioration of basic renal function in short- and long-term period. It seemed interesting to us to generalize the clinical data of general surgical patients treatment, which were need to use renal replacement therapy for acute renal failure in postoperative period. The analysis made us possible to draw conclusions that can broaden our understanding of the causes, course and outcomes of acute renal failure in such a patients.
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Affiliation(s)
- T V Marchenko
- Petrovsky Russian Research Centre for Surgery, Moscow, Russia
| | - V V Nikoda
- Petrovsky Russian Research Centre for Surgery, Moscow, Russia
| | - E A Lishova
- Petrovsky Russian Research Centre for Surgery, Moscow, Russia
| | - A V Goncharova
- Petrovsky Russian Research Centre for Surgery, Moscow, Russia
| | - R B Mayachkin
- Petrovsky Russian Research Centre for Surgery, Moscow, Russia
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Peres LAB, Bredt LC, Cipriani RFF. Acute renal injury after partial hepatectomy. World J Hepatol 2016; 8:891-901. [PMID: 27478539 PMCID: PMC4958699 DOI: 10.4254/wjh.v8.i21.891] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2016] [Revised: 06/02/2016] [Accepted: 06/27/2016] [Indexed: 02/06/2023] Open
Abstract
Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury (AKI) should be considered as an important cause of increased morbidity and postoperative mortality. Difficulties in the data analysis related to postoperative AKI after liver resections are mainly due to the multiplicity of factors to be considered in the surgical patients, moreover, there is no consensus of the exact definition of AKI after liver resection in the literature, which hampers comparison and analysis of the scarce data published on the subject. Despite this multiplicity of risk factors for postoperative AKI after partial hepatectomy, there are main factors that clearly contribute to its occurrence. First factor relates to large blood losses with renal hypoperfusion during the operation, second factor relates to the occurrence of post-hepatectomy liver failure with consequent distributive circulatory changes and hepatorenal syndrome. Eventually, patients can have more than one factor contributing to post-operative AKI, and frequently these combinations of acute insults can be aggravated by sepsis or exposure to nephrotoxic drugs.
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Affiliation(s)
- Luis Alberto Batista Peres
- Luis Alberto Batista Peres, Department of Nephrology, University Hospital of Western Paraná, State University of Western Paraná, Cascavel, Paraná 85819-110, Brazil
| | - Luis Cesar Bredt
- Luis Alberto Batista Peres, Department of Nephrology, University Hospital of Western Paraná, State University of Western Paraná, Cascavel, Paraná 85819-110, Brazil
| | - Raphael Flavio Fachini Cipriani
- Luis Alberto Batista Peres, Department of Nephrology, University Hospital of Western Paraná, State University of Western Paraná, Cascavel, Paraná 85819-110, Brazil
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Romanovsky A, Morgan C, Bagshaw SM. Pathophysiology and management of septic acute kidney injury. Pediatr Nephrol 2014; 29:1-12. [PMID: 23400860 DOI: 10.1007/s00467-013-2427-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2012] [Revised: 01/22/2013] [Accepted: 01/23/2013] [Indexed: 02/06/2023]
Abstract
Acute kidney injury (AKI) is a commonly encountered complication in critically ill children and portends a worse prognosis. Sepsis-induced AKI (SAKI) is a leading contributor to AKI in children and significantly modifies the risk for less favorable outcome. It has increasingly become clear that SAKI represents a unique and distinct cause of AKI. Studies focused on renal hemodynamics, bioenergetics, and immune-mediated injury have provided further insights into the pathobiology of SAKI; however, many of the nuanced mechanisms remain incompletely understood. Although there have been numerous strategies evaluated for the prevention and management of SAKI, no specific intervention has proven unequivocally efficacious. Currently, the mainstays for managing SAKI focus on alleviating ongoing kidney damage by optimizing systemic and kidney hemodynamic support, avoiding nephrotoxins, and mitigating the anticipated complications of kidney failure. The timely referral for renal support to manage azotemia, metabolic derangements, and fluid accumulation remains critical for this population. The extracorporeal removal of inflammatory mediators has shown some potential benefit in limiting systemic and kidney immune-mediated injury; however, the precise role of these technologies in the management of SAKI has yet to be defined.
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Affiliation(s)
- Adam Romanovsky
- Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, 8440-122 Street, 3C1.12 Walter C. Mackenzie Centre, Edmonton, AB, T6G2B7, Canada
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Chatterjee PK, Yeboah MM, Dowling O, Xue X, Powell SR, Al-Abed Y, Metz CN. Nicotinic acetylcholine receptor agonists attenuate septic acute kidney injury in mice by suppressing inflammation and proteasome activity. PLoS One 2012; 7:e35361. [PMID: 22586448 PMCID: PMC3346807 DOI: 10.1371/journal.pone.0035361] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2011] [Accepted: 03/14/2012] [Indexed: 12/14/2022] Open
Abstract
Sepsis is one of the leading causes of acute kidney injury (AKI). Septic patients who develop acute kidney injury (AKI) are at increased risk of death. To date there is no effective treatment for AKI or septic AKI. Based on their anti-inflammatory properties, we examined the effects of nicotinic acetylcholine receptor agonists on renal damage using a mouse model of lipopolysaccharide (LPS)-induced AKI where localized LPS promotes inflammation-mediated kidney damage. Administration of nicotine (1 mg/kg) or GTS-21 (4 mg/kg) significantly abrogated renal leukocyte infiltration (by 40%) and attenuated kidney injury. These renoprotective effects were accompanied by reduced systemic and localized kidney inflammation during LPS-induced AKI. Consistent with these observations, nicotinic agonist treatment significantly decreased renal IκBα degradation and NFκB activation during LPS-induced AKI. Treatment of human kidney cells with nicotinic agonists, an NFκB inhibitor (Bay11), or a proteasome inhibitor (MG132) effectively inhibited their inflammatory responses following stimulation with LPS or TNFα. Renal proteasome activity, a major regulator of NFκB-mediated inflammation, was enhanced by approximately 50% during LPS-induced AKI and elevated proteasome activity was significantly blunted by nicotinic agonist administration in vivo. Taken together, our results identify enhanced renal proteasome activity during LPS-induced AKI and the suppression of both proteasome activity and inflammation by nicotinic agonists to attenuate LPS-induced kidney injury.
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Affiliation(s)
- Prodyot K. Chatterjee
- The Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America
| | - Michael M. Yeboah
- Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Oonagh Dowling
- The Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America
| | - Xiangying Xue
- The Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America
| | - Saul R. Powell
- The Center for Heart and Lung Research, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America
| | - Yousef Al-Abed
- The Center for Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America
| | - Christine N. Metz
- The Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America
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Takahashi K, Mizukami H, Kamata K, Inaba W, Kato N, Hibi C, Yagihashi S. Amelioration of acute kidney injury in lipopolysaccharide-induced systemic inflammatory response syndrome by an aldose reductase inhibitor, fidarestat. PLoS One 2012; 7:e30134. [PMID: 22253906 PMCID: PMC3257265 DOI: 10.1371/journal.pone.0030134] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2011] [Accepted: 12/09/2011] [Indexed: 12/26/2022] Open
Abstract
Background Systemic inflammatory response syndrome is a fatal disease because of multiple organ failure. Acute kidney injury is a serious complication of systemic inflammatory response syndrome and its genesis is still unclear posing a difficulty for an effective treatment. Aldose reductase (AR) inhibitor is recently found to suppress lipopolysaccharide (LPS)-induced cardiac failure and its lethality. We studied the effects of AR inhibitor on LPS-induced acute kidney injury and its mechanism. Methods Mice were injected with LPS and the effects of AR inhibitor (Fidarestat 32 mg/kg) before or after LPS injection were examined for the mortality, severity of renal failure and kidney pathology. Serum concentrations of cytokines (interleukin-1β, interleukin-6, monocyte chemotactic protein-1 and tumor necrosis factor-α) and their mRNA expressions in the lung, liver, spleen and kidney were measured. We also evaluated polyol metabolites in the kidney. Results Mortality rate within 72 hours was significantly less in LPS-injected mice treated with AR inhibitor both before (29%) and after LPS injection (40%) than untreated mice (90%). LPS-injected mice showed marked increases in blood urea nitrogen, creatinine and cytokines, and AR inhibitor treatment suppressed the changes. LPS-induced acute kidney injury was associated with vacuolar degeneration and apoptosis of renal tubular cells as well as infiltration of neutrophils and macrophages. With improvement of such pathological findings, AR inhibitor treatment suppressed the elevation of cytokine mRNA levels in multiple organs and renal sorbitol accumulation. Conclusion AR inhibitor treatment ameliorated LPS-induced acute kidney injury, resulting in the lowered mortality.
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Affiliation(s)
- Kazunori Takahashi
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Hiroki Mizukami
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Kosuke Kamata
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Wataru Inaba
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | | | | | - Soroku Yagihashi
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
- * E-mail:
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Sahu PK, Pal A, Panda J, Patnaik S. Diuretics induced uremia and nonrecovery of renal function in a patient with acute renal failure caused by sepsis. Indian J Pharmacol 2011; 43:603-4. [PMID: 22022011 PMCID: PMC3195138 DOI: 10.4103/0253-7613.84983] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2011] [Revised: 05/20/2011] [Accepted: 07/01/2011] [Indexed: 11/04/2022] Open
Abstract
Sepsis is a clinical syndrome related to severe infection and is characterized by systemic inflammation and injury to multiple organs and functional systems. Sepsis is one of the main causes of acute renal failure (ARF). Diuretics are frequently administered during ARF. However, there is scant evidence that diuretics provide any benefit to the patients with ARF. This case report highlights the occurrence of uremia and nonrecovery of renal function after administration of diuretics in a patient with ARF caused by sepsis. It is suggested that physicians should be cautious in prescribing diuretics to patients with ARF due to septicemia. Diuretics cause uremia and may lead to false diagnosis of chronic renal failure and nonrecovery of renal function. The patient may unnecessarily require prolonged dialysis.
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Affiliation(s)
- P K Sahu
- Department of Pharmacology, School of Pharmaceutical Sciences, Siksha O Anusandhan University, Bhubaneswar, Orissa, India
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Uyanik A, Unal D, Uyanik MH, Halici Z, Odabasoglu F, Altunkaynak ZB, Cadirci E, Keles M, Gundogdu C, Suleyman H, Bayir Y, Albayrak M, Unal B. The effects of polymicrobial sepsis with diabetes mellitus on kidney tissues in ovariectomized rats. Ren Fail 2010; 32:592-602. [PMID: 20486843 DOI: 10.3109/08860221003759478] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVES Sepsis model was used to understand the role of sustained hyperglycemia and ovariectomy, either separately or concomitantly, on the response of the activity of the nuclear factor kappa B (NF-kappaB) and the oxidative response in kidney. SUBJECTS Polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Diabetes was induced in female rats using administration of alloxan. The rats were divided into five groups: sham control (group 1), ovariectomy (group 2), ovariectomy + sepsis (group 3), ovariectomy + diabetes (group 4), and ovariectomy + diabetic + sepsis (group 5). RESULTS In kidney tissues, the levels of lipid peroxidation (LPO) and glutathione (GSH) and the activity of catalase (CAT) were higher for groups 3, 4, 5 than the control groups. Superoxide dismutase (SOD) activity was lower for groups 3, 4, 5 than the control groups. We determined that CLP produced injury evident in the kidneys of rats when compared to the control group, whereas the severity of the injury was higher in the diabetes + ovariectomy + CLP group when compared to the CLP group. In immunohistochemical staining, we determined that CLP operation increased NF-kappaB activation. In the ovariectomized, septic, and diabetic group, NF-kappaB activation was significantly higher than other groups. CONCLUSIONS Hyperglycemia and ovariectomy severely increased NF-kappaB activation and oxidant levels with the stages of our sepsis model. Ovariectomy resulted in general changes in metabolism, which are seen in the kidney with diabetes under sepsis conditions.
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Affiliation(s)
- Abdullah Uyanik
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Ataturk University, 25240, Erzurum, Turkey
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de Abreu KLS, Silva Júnior GB, Barreto AGC, Melo FM, Oliveira BB, Mota RMS, Rocha NA, Silva SL, Araújo SMHA, Daher EF. Acute kidney injury after trauma: Prevalence, clinical characteristics and RIFLE classification. Indian J Crit Care Med 2010; 14:121-8. [PMID: 21253345 PMCID: PMC3021827 DOI: 10.4103/0972-5229.74170] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is an uncommon but serious complication after trauma. The objective of this study was to evaluate the prevalence, clinical characteristics and outcome of AKI after trauma. PATIENTS AND METHODS This was a retrospective study performed from January 2006 to January 2008 in an emergency specialized hospital in Fortaleza city, northeast of Brazil. All patients with AKI admitted in the study period were included. Prevalence of AKI, clinical characteristics and outcome were investigated. RESULTS Of the 129 patients admitted to the intensive care unit (ICU), 52 had AKI. The mean age was 30.1 ± 19.2 years, and 79.8% were males. The main causes of AKI were sepsis in 27 cases (52%) and hypotension in 18 (34%). Oliguria was observed in 33 cases (63%). Dialysis was required for 19 patients (36.5%). Independent risk factors associated with AKI were abdominal trauma [odds ratio (OR) = 3.66, P = 0.027] and use of furosemide (OR = 4.10, P = 0.026). Patients were classified according to RIFLE criteria as Risk in 12 cases (23%), Injury in 13 (25%), Failure in 24 (46%), Loss in 1 (2%) and End-stage in 2 (4%). Overall in-hospital mortality was 95.3%. The main cause of death was sepsis (24%). Mortality was 100% among patients with AKI. CONCLUSIONS AKI is a fatal complication after trauma, which presented with a high mortality in the studied population. A better comprehension of factors associated with death in trauma-associated AKI is important, and more effective measures of prevention and treatment of AKI in this population are urgently needed.
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Affiliation(s)
- Krasnalhia Lívia S. de Abreu
- From:Division of Nephrology, Department of Internal Medicine, School of Medicine, Walter Cantídio University Hospital, Ceará, Brazil
| | - Geraldo B. Silva Júnior
- From:Division of Nephrology, Department of Internal Medicine, School of Medicine, Walter Cantídio University Hospital, Ceará, Brazil
| | - Adller G. C. Barreto
- From:Division of Nephrology, Department of Internal Medicine, School of Medicine, Walter Cantídio University Hospital, Ceará, Brazil
| | - Fernanda M. Melo
- From:Division of Nephrology, Department of Internal Medicine, School of Medicine, Walter Cantídio University Hospital, Ceará, Brazil
| | - Bárbara B. Oliveira
- From:Division of Nephrology, Department of Internal Medicine, School of Medicine, Walter Cantídio University Hospital, Ceará, Brazil
| | - Rosa M. S. Mota
- Department of Statistics, Science Center, Federal University of Ceará – UFC, Ceará, Brazil
| | - Natália A. Rocha
- From:Division of Nephrology, Department of Internal Medicine, School of Medicine, Walter Cantídio University Hospital, Ceará, Brazil
| | - Sônia L. Silva
- From:Division of Nephrology, Department of Internal Medicine, School of Medicine, Walter Cantídio University Hospital, Ceará, Brazil
- Department of Internal Medicine, School of Medicine, University of Fortaleza – UNIFOR, Fortaleza, Ceará, Brazil
| | - Sônia M. H. A. Araújo
- From:Division of Nephrology, Department of Internal Medicine, School of Medicine, Walter Cantídio University Hospital, Ceará, Brazil
| | - Elizabeth F. Daher
- From:Division of Nephrology, Department of Internal Medicine, School of Medicine, Walter Cantídio University Hospital, Ceará, Brazil
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10
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Maquigussa E, Arnoni CP, Cristovam PC, de Oliveira AS, Higa EMS, Boim MA. Escherichia coli lipopolysaccharide impairs the calcium signaling pathway in mesangial cells: role of angiotensin II receptors. Exp Biol Med (Maywood) 2010; 235:761-7. [DOI: 10.1258/ebm.2010.010006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Sepsis causes impaired vascular reactivity, hypotension and acute renal failure. The ability of the Escherichia coli endotoxin (lipopolysaccharide [LPS]) to impair agonist-induced contractility in mesangial cells, which contributes to LPS-induced renal dysfunction, was evaluated. Agonist-induced intracellular calcium ([Ca2+]i) mobilization was analyzed using angiotensin II (AngII). The effect of LPS on the levels of the renin–angiotensin system (RAS) components and the roles of vasodilatation-inducing molecules including AT2 receptor (AT2R) and nitric oxide (NO) in the cell reactivity were also evaluated. Confluent human mesangial cells (HMCs) were stimulated with LPS (0111-B4, 100 μg/mL). AngII-induced [Ca2+]i mobilization was measured by fluorometric analysis using Fura-2AM in the absence and presence of an AT2R antagonist (PD123319). The mRNA and protein levels for angiotensinogen, renin, angiotensin-converting enzyme, AT1R and AT2R were analyzed by realtime reverse transcriptase-polymerase chain reaction and Western blot, respectively. NO production was measured by the chemiluminescence method in the culture media after 24, 48 and 72 h of LPS incubation. After 24 h, LPS-stimulated HMCs displayed lower basal [Ca2+]i and an impaired response to AngII-induced rise in [Ca2+]i. LPS significantly increased AT2R levels, but did not cause significant alterations of RAS components. PD123319 restored both basal and AngII-induced [Ca2+]i peak, suggesting an involvement of AT2R in these responses. The expected increase in NO production was significant only after 72 h of LPS incubation and it was unaffected by PD123319. Results showed that LPS reduced the reactivity of HMCs to AngII and suggest that the vasodilatation induced by AT2R is a potential mediator of this response through a pathway independent of NO.
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Affiliation(s)
- Edgar Maquigussa
- Department of Medicine, Renal Division – Federal University of São Paulo, São Paulo, Brazil
| | - Carine P Arnoni
- Department of Medicine, Renal Division – Federal University of São Paulo, São Paulo, Brazil
| | - Priscila C Cristovam
- Department of Medicine, Renal Division – Federal University of São Paulo, São Paulo, Brazil
| | - Andrea S de Oliveira
- Department of Medicine, Renal Division – Federal University of São Paulo, São Paulo, Brazil
| | - Elisa M S Higa
- Department of Medicine, Renal Division – Federal University of São Paulo, São Paulo, Brazil
| | - Mirian A Boim
- Department of Medicine, Renal Division – Federal University of São Paulo, São Paulo, Brazil
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11
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Anzai A, Anzai T, Naito K, Kaneko H, Mano Y, Jo Y, Nagatomo Y, Maekawa Y, Kawamura A, Yoshikawa T, Ogawa S. Prognostic Significance of Acute Kidney Injury After Reperfused ST-Elevation Myocardial Infarction: Synergistic Acceleration of Renal Dysfunction and Left Ventricular Remodeling. J Card Fail 2010; 16:381-9. [DOI: 10.1016/j.cardfail.2009.12.020] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2009] [Revised: 12/18/2009] [Accepted: 12/30/2009] [Indexed: 01/18/2023]
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12
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Kamimoto M, Mizuno S, Ohnishi H, Mizuno-Horikawa Y. Type 2a sodium-phosphate co-transporter serves as a histological predictor of renal dysfunction and tubular apical damage in the kidneys of septic mice. ACTA ACUST UNITED AC 2009; 30:251-8. [PMID: 19729856 DOI: 10.2220/biomedres.30.251] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Acute renal failure (ARF) occurs in septic patients and is histologically characterized by tubular apical damages, including brush border breakdown. Nevertheless, little information is available to identify the apical injury at a molecular level. Type 2a Na-phosphate (Pi) co-transporter (NaPiT2a) is constitutively expressed by brush borders of proximal tubules under a healthy condition. Therefore, we investigated if NaPiT2a could be used as a negative marker to predict the renal dysfunction, using an animal model of septic ARF. After the treatment of lipopolysaccharide (LPS), mice manifested the tubular apical injury and renal dysfunction, as evidenced by the increase in blood urea nitrogen (BUN) levels. Immunohistochemical examination revealed that the expression of NaPiT2a by renal proximal tubules became faint, being reciprocal to the development of tubular hypoxia during sepsis. Inversely, the loss in apical NaPiT2a was restored in a regenerating stage, associated with the recovery from renal hypoxia. Overall, there was a negative correlation between the NaPiT2a expression and BUN levels or tubular injury scores in septic mice. Our data indicate that the loss of NaPiT2a is a reliable marker for predicting the progression of septic ARF, while local hypoxia might be involved in the decrease of NaPiT2a expression.
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Affiliation(s)
- Miyuki Kamimoto
- Department of Biochemistry and Molecular Biology, Osaka University, Japan
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13
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Nakamura A, Niimi R, Yanagawa Y. Protection from sepsis-induced acute renal failure by adenoviral-mediated gene transfer of 2-adrenoceptor. Nephrol Dial Transplant 2009; 25:730-7. [DOI: 10.1093/ndt/gfp561] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
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14
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Höcherl K, Schmidt C, Kurt B, Bucher M. Inhibition of NF-kappaB ameliorates sepsis-induced downregulation of aquaporin-2/V2 receptor expression and acute renal failure in vivo. Am J Physiol Renal Physiol 2009; 298:F196-204. [PMID: 19828675 DOI: 10.1152/ajprenal.90607.2008] [Citation(s) in RCA: 70] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Acute renal failure (ARF) is frequently associated with polyuria and urine concentration defects and it is a severe complication of sepsis because it increases the mortality rate. Inhibition of NF-kappaB activation has been suggested to provide a useful strategy for the treatment of septic shock. However, the impact on sepsis-induced ARF is still unclear. Therefore, we examined the effect of pyrrolidine dithiocarbamate (PDTC) and of small interfering RNA (siRNA) silencing NF-kappaB p50/p105 on sepsis-induced downregulation of vasopressin V(2) receptors and aquaporin (AQP)-2 channels using a cecal ligation and puncture (CLP) mouse model. CLP caused a time-dependent downregulation of renal vasopressin V(2) receptor and of AQP2 expression without alterations in plasma vasopressin levels. Renal activation of NF-kappaB in response to CLP was attenuated by PDTC pretreatment, which also attenuated the downregulation of V(2) receptor and AQP2 expression. Furthermore, a strong nuclear staining for the NF-kappaB p50 subunit throughout the whole kidney in response to CLP was observed. siRNA against NF-kappaB p50 attenuated the CLP-induced nuclear translocation of the p50 subunit and the CLP-induced downregulation of V(2) receptor and AQP2 expression. Additionally, PDTC and siRNA pretreatment inhibited the CLP-induced increase in renal TNF-alpha and IL-1beta concentration and NOS-2 mRNA abundance. Moreover, PDTC and siRNA pretreatment ameliorated CLP-induced hypotension and ARF. Our findings suggest that NF-kappaB activation is of importance for the downregulation of AQP2 channel and vasopressin V(2) receptor expression during sepsis. In addition, our data indicate that NF-kappaB inhibition ameliorates sepsis-induced ARF.
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Affiliation(s)
- Klaus Höcherl
- Institut für Physiologie, Universität Regensburg, Universitätsstr. 31, D-93040 Regensburg, Germany.
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15
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Affiliation(s)
- J Gary Abuelo
- Division of Kidney Disease and Hypertension, Department of Medicine, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
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16
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Kadiroglu AK, Sit D, Atay AE, Kayabasi H, Altintas A, Yilmaz ME. The evaluation of effects of demographic features, biochemical parameters, and cytokines on clinical outcomes in patients with acute renal failure. Ren Fail 2007; 29:503-8. [PMID: 17497476 DOI: 10.1080/08860220701274991] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
AIM To evaluate the effects of cytokines, biochemical parameters and demographic features on clinical outcomes of acute renal failure (ARF). PATIENTS AND METHODS 59 patients with acute renal failure (28 men, 31 women) were enrolled to the study. Cytokines, biochemical parameters, and complete blood count were measured. Patients were divided into two groups: as survivors (group 1, n = 46) and nonsurvivors (group 2, n = 13). RESULTS Mean age of patients were 52.3 +/- 17.9 years. 46 patients survived (77.9%) and 13 patients died (22.1%). There was a statistically significant relationship between IL-2R, IL-6, and TNF-alpha levels and mortality rates (p = 0.004, p = 0.016, p = 0.020, respectively) and between TC levels and mortality rates (p = 0.041). In multivariable logistic regression analysis, the effects of proinflammatory cytokines (IL-1beta, IL-2R, IL-6, TNFalpha, CRP, and ESR) on the clinical outcomes in ARF was observed to be statistically significant (r = 0.341, p = 0.005). CONCLUSION We realized that in totally demographic features (male gender, advanced age, poor nutritional status), biochemical parameters (TC, albumin, and hemoglobin) and cytokine levels (IL-2R, IL-6, TNF-alpha), CRP and ESR may be predictive factors for mortality in patients with ARF.
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Affiliation(s)
- Ali Kemal Kadiroglu
- Department of Internal Medicine, Medicine Faculty of Dicle University, Diyarbakir, Turkey.
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17
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Kohli HS, Bhat A, Jairam A, Aravindan AN, Sud K, Jha V, Gupta KL, Sakhuja V. Predictors of mortality in acute renal failure in a developing country: a prospective study. Ren Fail 2007; 29:463-9. [PMID: 17497470 DOI: 10.1080/08860220701260651] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
Acute renal failure (ARF) occurs in wide range of conditions, making the evaluation of its prognosis a difficult task. Data regarding prognostic factors in ARF in a general population in developing countries are scarce. The objective of the study was to describe predictors of mortality in ARF that are relevant in the developing world. This prospective study was carried out over a one-year period; all hospitalized adults with ARF were included in the study. Predictors of mortality studied included causes of ARF, pre-existing diseases, and severity as well as complications of ARF. Of 33,301 patients admitted during the study period, 294 (0.88%) were either admitted with or developed ARF after hospitalization. Mean age was 43.9 +/- 16.9 (18-86 yrs). Sepsis was the most common cause (63.26%). Pre-existing diseases like cardiovascular disease (CVSD), respiratory system disease (RSD), central nervous system disease (CNSD), hypertension, diabetes mellitus (DM), and malignancy were significantly higher in elderly as compared to younger patients. On univariate analysis sepsis, hypoperfusion as a cause of ARF and hospital-acquired ARF were associated with higher mortality. Pre-existing diseases viz. RSD, CVSD, CNSD, and DM had higher mortality. Among the severity and complications of ARF, oliguria, bleeding and infection during the course of ARF and critical illness were predictors of poor outcome. Age > 60 yrs was associated with significantly higher mortality. However, on multivariate analysis, only critical illness (odds ratio 37.3), age > 60 years (odds ratio of 5.6), and sepsis as cause of ARF (odds ratio of 2.6) were found to be independent predictors of mortality.
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18
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Tracz MJ, Juncos JP, Grande JP, Croatt AJ, Ackerman AW, Rajagopalan G, Knutson KL, Badley AD, Griffin MD, Alam J, Nath KA. Renal hemodynamic, inflammatory, and apoptotic responses to lipopolysaccharide in HO-1-/- mice. THE AMERICAN JOURNAL OF PATHOLOGY 2007; 170:1820-30. [PMID: 17525251 PMCID: PMC1899452 DOI: 10.2353/ajpath.2007.061093] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Lipopolysaccharide (LPS) induces the stress-responsive gene heme oxygenase-1 (HO-1). The present study examined the significance of HO-1 in response to LPS. In HO-1(-/-) mice, as compared with HO-1(+/+) mice, LPS provoked a greater reduction in glomerular filtration rate and renal blood flow, increased renal cytokine expression, and increased activation of nuclear factor (NF)-kappaB. Conversely, HO-1-overexpressing renal epithelial cells, exposed to LPS, exhibited a blunted activation of NF-kappaB and less phosphorylation of its inhibitor, IkappaB. In HO-1(-/-) mice, as compared with HO-1(+/+) mice, LPS provoked markedly greater elevations in serum levels of Th1 cytokines, Th2 cytokines, chemokines, and cytokines that stimulate bone marrow progenitors. The liver, a major source of serum cytokines, showed an increased activation of NF-kappaB in LPS-treated HO-1(-/-) mice. In addition, LPS provoked widespread apoptosis of immune cells in the spleen and thymus in HO-1(-/-) mice but not in HO-1(+/+) mice. We conclude that HO-1 deficiency exhibits a heightened and dysregulated inflammatory response to LPS accompanied by greater impairment in renal hemodynamic response and widespread apoptosis of immune cells. Because polymorphisms in the HO-1 gene with diminished HO activity predispose to human disease, we speculate that our findings may be relevant to the clinical outcome in patients with sepsis syndromes.
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Affiliation(s)
- Michal J Tracz
- Division of Nephrology and Hypertension, Department of Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
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Kohli HS, Bhat A, Sud K, Jha V, Gupta KL, Sakhuja V. Spectrum of renal failure in elderly patients. Int Urol Nephrol 2007; 38:759-65. [PMID: 17245550 DOI: 10.1007/s11255-006-0089-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2005] [Accepted: 03/28/2006] [Indexed: 11/30/2022]
Abstract
This prospective study was undertaken to study the spectrum of renal failure and the outcome in elderly patients. Patients included in the study group were elderly (age>60 years) who either attended outpatient renal clinic and or were hospitalized. Renal failure was classified as acute renal failure (ARF), rapidly progressive renal failure (RPRF) and chronic renal failure (CRF). A total of 4255 elderly patients were seen, of these 236 (5.5%) had renal failure. Mean age was 65.1+/-4.2 years (60-86 years). CRF was the commonest, seen in 137 (58.1%) followed by ARF 69 (29.2%) and RPRF in 30 (12.7%) patients. Diabetic nephropathy was the commonest cause of CRF, seen in 58.4% followed by chronic interstitial nephritis in 9.5% and chronic glomerulonephritis in 8.7% of patients. Of 137 patients 53 (38.7%) presented in end stage renal disease (ESRD). Of these 41 (77.3%) were initiated on maintenance hemodialysis and 12 (22.6%) on continuous ambulatory peritoneal dialysis. Only 15 patients were on dialytic support at the end of 1 year. Sepsis contributed to ARF in 75.4% of cases. Forty of 69 patients (57.9%) needed dialytic support. Forty (57.9%) were critically ill, defined as presence of two or more organ system failures (excluding renal failure). Forty two patients (60.9%) died patients. Acute interstitial nephritis (AIN) was the commonest cause of RPRF seen in 10 (33.3%) patients followed by vasculitis in 7 (23.3%). Myeloma cast nephropathy contributed towards RPRF in 20% of patients. Of 30 patients, 10 (33.3%) reached ESRD at end of 3 months of follow up, 4 (13.3%) died due to sepsis. Only 2 showed complete recovery while 14 (46.6%) had partial improvement. AIN patients had a relatively better outcome.
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20
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Kohli HS, Bhat A, Aravindan AN, Sud K, Jha V, Gupta KL, Sakhuja V. Predictors of mortality in elderly patients with acute renal failure in a developing country. Int Urol Nephrol 2007; 39:339-44. [PMID: 17203349 DOI: 10.1007/s11255-006-9137-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2006] [Accepted: 10/22/2006] [Indexed: 01/31/2023]
Abstract
This prospective study was undertaken to systematically analyze the predictors of mortality in the elderly in a developing country. All elderly patients with ARF hospitalized at this tertiary care centre over 1 year were studied. Various predictors analyzed were hospital-acquired ARF, causative factors of ARF, preexisting hypertension and diabetes mellitus, severity of renal failure (initial and peak serum creatinine, need for dialysis), and complications of ARF: infection during the course of illness; serum albumin levels and critical illness defined as presence of two or more organ system failures excluding renal failure. Of 33,301 patients admitted, 4,255 (12.7%) were elderly. Of these 69 (1.6%) had ARF. On analysis of the whole group, both young and elderly, age >60 years had an independent predictor of mortality (odds ratio 5.6, P = 0.001). Forty-two of the 69 (60.9%) elderly ARF patients died. The mortality was significantly increased in those elderly with hospital-acquired ARF (79.2%, P = 0.027), those with sepsis as a cause of ARF (71.2%, P = 0.004), those who required dialysis (72.5%, P = 0.022), those developing an infection during the course of ARF (87.9%, P = 0.000) and in those with a critical illness (90.0%, P = 0.00). On logistic regression analysis of those variables that were significant on univariate analysis, only critical illness (odds ratio 9.97) and infection during course (odds ratio 9.72) were the independent predictors of mortality. To conclude, ARF complicates only 1.6% of hospitalized elderly patients but is associated with a high mortality rate of 61%. Infection during the course of illness and critical illness were the independent predictors of mortality.
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21
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Silva Júnior GBD, Daher EDF, Mota RMS, Menezes FA. Risk factors for death among critically ill patients with acute renal failure. SAO PAULO MED J 2006; 124:257-63. [PMID: 17262155 PMCID: PMC11068301 DOI: 10.1590/s1516-31802006000500004] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2005] [Accepted: 08/07/2006] [Indexed: 11/21/2022] Open
Abstract
CONTEXT AND OBJECTIVE Acute renal failure is a common medical problem, with a high mortality rate. The aim of this work was to investigate the risk factors for death among critically ill patients with acute renal failure. DESIGN AND SETTING Retrospective cohort at the intensive care unit of Hospital Universitário Walter Cantídio, Fortaleza. METHODS Survivors and non-survivors were compared. Univariate and multivariate analyses were performed to establish risk factors for death. RESULTS Acute renal failure occurred in 128 patients (33.5%), with mean age of 49 +/- 20 years (79 males; 62%). Death occurred in 80 (62.5%). The risk factors most frequently associated with death were hypotension, sepsis, nephrotoxic drug use, respiratory insufficiency, liver failure, hypovolemia, septic shock, multiple organ dysfunction, need for vasoactive drugs, need for mechanical ventilation, oliguria, hypoalbuminemia, metabolic acidosis and anemia. There were negative correlations between death and: prothrombin time, hematocrit, hemoglobin, systolic blood pressure, diastolic blood pressure, arterial pH, arterial bicarbonate and urine volume. From multivariate analysis, the independent risk factors for death were: need for mechanical ventilation (OR = 3.15; p = 0.03), hypotension (OR = 3.48; p = 0.02), liver failure (OR = 5.37; p = 0.02), low arterial bicarbonate (OR = 0.85; p = 0.005), oliguria (OR = 3.36; p = 0.009), vasopressor use (OR = 4.83; p = 0.004) and sepsis (OR = 6.14; p = 0.003). CONCLUSIONS There are significant risk factors for death among patients with acute renal failure in intensive care units, which need to be identified at an early stage for early treatment.
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Affiliation(s)
- Geraldo Bezerra da Silva Júnior
- Intensive Care Unit of Hospital Universitário Walter Cantídio, School of Medicine, Universidade Federal do Ceará, Rua Mário Alencar Araripe 61, Fortaleza, Ceará, Brazil.
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22
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Nakamura A, Imaizumi A, Niimi R, Yanagawa Y, Kohsaka T, Johns EJ. Adenoviral delivery of the β2-adrenoceptor gene in sepsis: a subcutaneous approach in rat for kidney protection. Clin Sci (Lond) 2005; 109:503-11. [PMID: 16076286 DOI: 10.1042/cs20050088] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Successful gene therapy requires gene delivery that is efficient, has an optimal route of administration and has biosafety. The aims of the present study were to evaluate the safety and applicability of the subcutaneous delivery route for adenoviral transgenes containing the human β2-adrenoceptor (adeno-β2-AR) and to investigate whether this approach prevented renal dysfunction in a rat model of endotoxaemic shock induced by LPS (lipopolysaccharide). Subcutaneous administration of adeno-β2-AR (a total of 1010 viral particles) significantly increased β-AR density in the kidney, lung and liver, but was without effect on physiological and plasma biochemical parameters. Moreover, this dose of virus did not cause any of the potential toxic responses of viral administration, such as inflammation and tissue TNF (tumour necrosis factor)-α expression. Although the LPS challenge caused a decrease in glomerular filtration rate, fractional excretion of sodium and renal β-AR density in all groups, the reduction in renal function was significantly less in the rats given adeno-β2-AR compared with non-treated rats. Thus, although further evaluation will be required, this initial study demonstrated that the subcutaneous injection of adeno-β2-AR was efficient, comparatively non-pathogenic and potentially therapeutic to deal with acute renal failure associated with sepsis.
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Affiliation(s)
- Akio Nakamura
- Department of Paediatrics, Teikyo University School of Medicine, Tokyo 173, Japan.
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Abstract
Despite the commonly accepted indications for hemodialysis and extracorporeal depuritive techniques, some clinicians have come to rely on blood purification for clinical states where the targeted substance for removal differs from uremic waste products. Over the last decade, a number of studies have emerged to help define the application of extracorporeal blood purification (ECBP) to these "nonuremic" indications. This review describes the application of extracorporeal blood purification in clinical states including sepsis, rhabdomyolysis, congestive heart failure, hepatic failure, tumor lysis syndrome, adult respiratory distress syndrome, intravenous contrast exposure, and lactic acidosis. Additional comments are provided to review existing literature on thermoregulation and osmoregulation, including acute brain injury.
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Affiliation(s)
- Andrew E Briglia
- Department of Medicine, Division of Nephrology, University of Maryland, Baltimore, Maryland 21201, USA.
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Molitoris BA. Renal blood flow in sepsis: a complex issue. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2005; 9:327-8. [PMID: 16137373 PMCID: PMC1269462 DOI: 10.1186/cc3740] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The clinical complexity of sepsis and the regional variability in renal blood flow present a difficult challenge for the clinician or investigator in understanding the role and clinical importance of reduced blood flow in the pathophysiology of sepsis-induced acute renal failure. Understanding the role of regional microvasculature flow and interactions between endothelium and white blood cells in the local delivery of oxygen and substrates is of critical importance. Therefore, measuring total renal blood flow may not permit an adequate understanding of the role of altered hemodynamics in septic patients who develop acute renal failure.
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Affiliation(s)
- Bruce A Molitoris
- Division of Nephrology, Department of Medicine and the Indiana Center for Biological Microscopy, Indiana University School of Medicine, Indianapolis, IN, USA.
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25
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d'Avila DO, Cendoroglo Neto M, dos Santos OFP, Schor N, Poli de Figueiredo CE. Acute renal failure needing dialysis in the intensive care unit and prognostic scores. Ren Fail 2004; 26:59-68. [PMID: 15083924 DOI: 10.1081/jdi-120028552] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
BACKGROUND Generic prognostic scores used in acute renal failure (ARF) give imprecise results; disease-specific indices applied to distinct populations or intensive care practices becomes inaccurate. The current study evaluates the adequacy of prognostic scores, in patients with severe ARF needing dialysis. METHODS Known generic (APACHE II) and disease-specific (ATN-ISS) indices were applied to a cohort (n = 280) with ARF needing dialysis, under intensive care. Possible risk factors as causal factors, organ dysfunctions and clinical variables were examined, and a local index assembled by multivariate logistic regression analysis. Area under the receiver operating characteristics (ROC) curves evaluated the indices discriminating capacity. Goodness-of-fit testing and linear regression analysis appraised calibration. Validation was accomplished by the bootstrapping technique. The end-point was hospital mortality. RESULTS Overall mortality was 85%. Female gender < 44 years (OR: 0.29; 95% CI: 0.10-0.84), liver/obstructive biliary disease (OR: 6.03; 95% CI: 1.65-22.08), being conscious (OR: 0.49; 95% CI: 0.21-1.14), use of vasoactive drug (OR: 3.13; 95% CI: 1.25-7.83), respiratory dysfunction (OR: 5.20; 95% CI: 1.25-7.83) or sepsis (OR: 2.62; 95% CI: 1.14-6.02) were associated with outcome. Areas under the ROC curve of 0.815, 0.652 and 0.814; Goodness-of-fit test P = 0.593, P < 0.001 and P = 0.002; and linear regression R2 = 0.973, R2 = 0.526 and R2 = 0.919 for the local index, APACHE II and ATN-ISS, respectively, indicate better performance by the local index. The local index median area under the ROC curve, by bootstrapping, was 0.820 (95% CI: 0.741-0.907). CONCLUSIONS APACHE II score was inaccurate, and ATN-ISS poorly calibrated. When mortality or intensive care practices significantly deviate, local scores may better evaluate prognosis in severe ARF.
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Affiliation(s)
- Domingos O d'Avila
- Programa de Pós-Graduação em Clínica Médica (Nefrologia), Faculdade de Medicina, PUCRS, Porto Alegre, Brazil.
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26
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Affiliation(s)
- Robert W Schrier
- Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
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27
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Affiliation(s)
- N Lameire
- Renal Division, University Hospital, Ghent, Belgium.
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28
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Yegenaga I, Hoste E, Van Biesen W, Vanholder R, Benoit D, Kantarci G, Dhondt A, Colardyn F, Lameire N. Clinical characteristics of patients developing ARF due to sepsis/systemic inflammatory response syndrome: results of a prospective study. Am J Kidney Dis 2004; 43:817-24. [PMID: 15112172 DOI: 10.1053/j.ajkd.2003.12.045] [Citation(s) in RCA: 127] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
BACKGROUND Acute renal failure (ARF) in patients with sepsis provokes high mortality and financial cost. In this prospective study, we collected characteristics of patients in the intensive care unit (ICU) who developed sepsis/systemic inflammatory response syndrome (SIRS) to analyze differences between those who subsequently did or did not develop ARF. METHODS All patients admitted to the ICU of the University Hospital Gent, Belgium, between January 1, 2001, and December 31, 2001, who developed sepsis/SIRS were included if they had a serum creatinine level less than 2 mg/dL (<177 micromol/L). RESULTS Of 2,442 patients admitted to the ICU, 257 patients developed sepsis/SIRS. Of those, 29 patients (11%) developed ARF. In a univariate analysis, age, central venous pressure (CVP), and serum creatinine and blood urea nitrogen levels were greater (P = 0.003, P = 0.006, P < 0.001, and P < 0.001, respectively), whereas mean arterial and diastolic blood pressures, 24-hour urinary output, arterial pH, bicarbonate level, thrombocyte count, albumin level, and prothrombin time were lower (P = 0.05, P = 0.004, P = 0.005, P = 0.03, P = 0.009, P = 0.037, P = 0.05, and P = 0.006, respectively) in the ARF group. Prevalence of diabetes, sex, and need for ventilation were not different between the ARF and no-ARF groups, but in the ARF group, diuretic use, vasopressor use, and presence of primary hepatic failure were more prevalent (P = 0.001 for each). In a multivariate analysis, age, serum creatinine level, CVP, and presence of liver failure significantly contributed to a logistic regression model for ARF. CONCLUSION Several parameters already were disturbed at the first day of SIRS/sepsis in patients who later developed ARF. Older age, elevated serum creatinine level despite elevated CVP, and presence of hepatic failure are predictive for ARF in septic patients.
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Affiliation(s)
- Itir Yegenaga
- Department of Nephrology, Internal Medicine, Kocaeli University Medical School, Izmit, Turkey
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Yelken BB, Görenek ES, Uzuner K, Aydin Y, Elmas C. Effects of Dopexamine on Rat Cardiorenal Functions during Lipopolysaccharide-Induced Experimental Sepsis. J Int Med Res 2004; 32:109-17. [PMID: 15080013 DOI: 10.1177/147323000403200202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
We aimed to test the protective effect of dopexamine on renal function and systemic haemodynamics in rats with induced sepsis. Female Sprague-Dawley rats were randomized into three equal groups: group 1 (control, received 3% creatinine throughout the experiment); group 2 (sepsis, received 3% creatinine and Escherichia coli lipopolysaccharide [LPS] endotoxin [8 mg/kg per h]); and group 3 (sepsis plus dopexamine, received 3% creatinine, E. coli LPS and dopexamine [1 μg/kg per min]). Time-adjusted heart rate, systolic, diastolic and mean arterial pressures, urine volume and glomerular filtration rate (from creatinine clearance) were recorded. After bacterial infusion heart rate increased and mean arterial pressure decreased; the fall in mean arterial pressure was less pronounced with dopexamine (group 3) than without (group 2). Dopexamine also induced significant and moderate increases in urine volume and heart rate, respectively. We concluded that dopexamine has some positive inotropic-chronotropic effects and induces favourable responses in renal function.
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Affiliation(s)
- B B Yelken
- Department of Anesthesiology and ICU, Medical Faculty, Osmangazi University, Eskisehir, Turkey.
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Abstract
PURPOSE OF REVIEW Acute renal failure is commonly present in patients with sepsis, shock, trauma, burn injury, or multi-organ dysfunction syndrome. Acute renal failure is an independent risk factor contributing to increased hospital mortality. The major complications associated with acute renal failure include metabolic derangement and protein catabolism. The purpose of this article is to review the literature between 2001 and December 2003, to determine whether newer studies have provided a better understanding of the optimization of caloric and protein delivery to critically ill patients with acute renal failure receiving continuous renal replacement therapy. RECENT FINDINGS Continuous renal replacement therapy is now widely used in the intensive care unit to manage patients with acute renal failure, because it is better tolerated than intermittent hemodialysis by patients who are hemodynamically unstable. Although continuous renal replacement therapy is highly efficient in the removal of toxins and metabolic wastes, it may also lead to an excessive loss of nutrients, which include intact protein and amino acids. Data describing the optimal nutritional support regimen for patients receiving continuous renal replacement therapy are very limited. SUMMARY The results and findings from this review may help clinicians to individualize caloric and protein delivery for patients with acute renal failure. The ultimate goal is to tailor the regimen towards the needs of each individual patient in order to maximize the benefit of nutritional support, in the hope of improving patient survival.
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Affiliation(s)
- Lingtak-Neander Chan
- Departments of Pharmacy Practice and Medicine, Section of Respiratory and Critical Care Medicine, Colleges of Pharmacy and Medicine, University of Illinois at Chicago, 833 South Wood Street (MC 886), Chicago, IL 60612, USA.
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31
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Affiliation(s)
- Ravindra L Mehta
- Divisions of Nephrology, Departments of Medicine, University of California San Diego for the PICARD Study Group,USA.
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Watanabe T, Yoshikawa H, Abe Y, Yamazaki S, Uehara Y, Abe T. Renal involvement in children with influenza A virus infection. Pediatr Nephrol 2003; 18:541-544. [PMID: 12698331 DOI: 10.1007/s00467-003-1143-z] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2002] [Revised: 01/28/2003] [Accepted: 01/30/2003] [Indexed: 12/29/2022]
Abstract
Renal involvement in influenza A virus infection has been rarely reported. To define the clinical characteristics and the factors contributing to the development of renal involvement in influenza A virus infection, we reviewed the clinical characteristics, laboratory data, pediatric risk of mortality (PRISM) score, and the number of systemic inflammatory response syndrome (SIRS) criteria and dysfunctional organs in 45 hospitalized children with influenza A virus infection. Eleven (24.4%) patients had renal involvement. All patients with renal involvement suffered from sepsis and multiple organ dysfunction syndrome (MODS) and 5 developed acute renal failure (ARF). The incidences of dehydration, hypotension, disseminated intravascular coagulation (DIC), and rhabdomyolysis were significantly higher in patients with renal involvement. PRISM scores, the numbers of SIRS criteria and dysfunctional organs, and mortality rate were also higher in patients with renal involvement. Influenza A RNA was absent in the renal tissues of 3 patients with ARF. These results suggested that renal involvement in influenza A virus infection occurred in patients with sepsis and MODS; dehydration, hypotension, DIC, and rhabdomyolysis were factors contributing to its development; direct viral injury to the kidney did not seem to occur in influenza A virus infection.
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Affiliation(s)
- Toru Watanabe
- Department of Pediatrics, Niigata City General Hospital, Niigata, Japan.
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Formica M, Olivieri C, Livigni S, Cesano G, Vallero A, Maio M, Tetta C. Hemodynamic response to coupled plasmafiltration-adsorption in human septic shock. Intensive Care Med 2003; 29:703-8. [PMID: 12665998 DOI: 10.1007/s00134-003-1724-0] [Citation(s) in RCA: 68] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2002] [Accepted: 02/17/2003] [Indexed: 12/22/2022]
Abstract
OBJECTIVE The objective was to examine the effect of repeated applications of coupled plasmafiltration-adsorption on the hemodynamic response in septic shock patients hospitalized in intensive care units (ICUs). DESIGN Prospective, intention-to-treat. SETTING General ICU of a tertiary care, non-teaching, 400-bed, city hospital. PATIENTS AND PARTICIPANTS Twelve consecutive mechanically ventilated septic shock patients, with or without concomitant acute renal failure (ARF). INTERVENTION A median of 10 consecutive sessions (prescribed treatment time: 10 h/session; delivered duration: 8.43+/-1.37 h/min) of coupled plasmafiltration-adsorption for each patient. MEASUREMENTS AND RESULTS Mean arterial pressure (77.2+/-12.5 [CI 95%; 74.5-79.8] vs. 83.3+/-14.1 [CI 95%; 80.3-86.3] mm Hg; [ p<0.001]), cardiac index (4.03+/-0.89 [CI 95%; 3.83-4.22] vs. 3.46+/-0.82 [CI 95%; 3.28-3.64] L/m(2)/min; [ p<0.001]), systemic vascular resistance index (1,388+/-496 [CI 95%; 1,278-1,497] vs. 1,753+/-516 [CI 95%; 1,639-1,867] dynes x s/cm(5); [ p<0.001]), PO2/FIO2 ratio (204+/-87 [CI 95%; 185-223] vs. 238+/-82 [CI 95%; 220-256]; [ p<0.001]), significantly improved during 100 global treatments (pre- vs. post-treatment values). Intra-thoracic blood volume and extra-vascular lung water did not change across treatments. Vasopressor requirement was reduced: norepinephrine decrease from an infusion rate of 0.13+/-0.07 (CI 95%; 0.06-0.16) to 0 gamma/kg/min after a mean of 5.3+/-2.7 sessions. C reactive protein (CRP) significantly decreased (from 29.3+/-7.3 vs. 7.9+/-4.8; p<0.0001) during treatment. Survival was 90% at day 28 and 70% at day 90. CONCLUSION Coupled plasmafiltration-adsorption was a feasible and safe extracorporeal treatment and exerted a remarkable improvement in the hemodynamics, the pulmonary function, and the outcome in septic shock patients with or without concomitant ARF.
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Affiliation(s)
- Marco Formica
- Divisione di Nefrologia e Dialisi, Ospedale Torino Nord Emergenza, San Giovanni Bosco, Turin, Italy.
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Abstract
Acute renal failure (ARF) is associated with morbidity and mortality in excess of 50% in the intensive care unit (ICU) setting. A variety of outcome measures have been described in published reports of ARF, however, the studies often do not distinguish between clinical outcomes and surrogate endpoints. Multiple factors can influence these outcomes, including variations in practice. It is important to be aware of the potential effects of these factors when clinical trials are planned and executed for ARF patients. For any intervention trial, knowledge of the natural history of the disease and process of care informs the design and conduct of the trial. Standardization of a definition for ARF and of the criteria for initiation, frequency, duration, and withdrawal of dialysis support would be of great benefit. This article provides a critical appraisal of outcomes research in ARF and describes an approach for selecting appropriate endpoints for future clinical research in ARF.
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Affiliation(s)
- Ravindra L Mehta
- Department of Medicine, University of California, San Diego, CA, USA.
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Avasthi G, Sandhu JS, Mohindra K. Acute renal failure in medical and surgical intensive care units--a one year prospective study. Ren Fail 2003; 25:105-13. [PMID: 12617338 DOI: 10.1081/jdi-120017473] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
The spectrum of acute renal failure is different in intensive care unit (ICU) vs. non-ICU population. This one year prospective study carried out in medical and surgical intensive care units showed an incidence of 8.6% of acute renal failure. The incidence of acute renal failure was highest in medical ICU (17.2%) followed by burns ICU (5.3%), pulmonary ICU (5.2%), stroke ICU (4.4%), surgical ICU (3.1%) and least in coronary ICU (1.3%). The acute renal failure was attributable to medical causes in 68% followed by surgery and trauma in 21.2%, burns in 5.6% and pregnancy related in 5.1%. In majority, acute renal failure was multifactorial. Septicemia was the commonest cause in both medical (50%) and surgical (86%) ICUs. Multi organ system failure was present in 77.3% of patients with acute renal failure. Approximately 40% required dialysis. The mortality of acute renal failure was 62% and the mortality was correlated with the number of organ system failures, presence of oliguria and septicemia. The mean ICU stay was significantly shorter in the non-survivors.
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Affiliation(s)
- Gurcharan Avasthi
- Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
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36
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Affiliation(s)
- Biff F Palmer
- Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical School, Dallas 75390-8856, USA.
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Wang W, Falk SA, Jittikanont S, Gengaro PE, Edelstein CL, Schrier RW. Protective effect of renal denervation on normotensive endotoxemia-induced acute renal failure in mice. Am J Physiol Renal Physiol 2002; 283:F583-7. [PMID: 12167611 DOI: 10.1152/ajprenal.00270.2001] [Citation(s) in RCA: 65] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Acute renal failure (ARF) contributes substantially to the high morbidity and mortality observed during endotoxemia. We hypothesized that selective blockade of the renal nerves would be protective against ARF during the early (16 h) stage of endotoxemia [5 mg lipopolysaccharide (LPS)/kg ip in mice]. At 16 h after LPS, there was no change in mean arterial pressure, but plasma epinephrine (4,604 +/- 719 vs. 490 +/- 152 pg/ml, P < 0.001), norepinephrine (2,176 +/- 306 vs. 1,224 +/- 218 pg/ml, P < 0.05), and plasma renin activity (40 +/- 5 vs. 27 +/- 2 ng x ml(-1) x h(-1), P < 0.05) were higher in the LPS-treated vs. control mice. The high plasma renin activity level decreased to the control level with renal denervation in endotoxemic mice. After intravenous injection of phentolamine (200 microg/kg), the decrement in mean arterial pressure was significantly greater in LPS-treated vs. control mice (19.4 +/- 3.5 vs. 8.1 +/- 1.5 mmHg, P < 0.01). Sixteen hours after LPS administration, there were significant decreases in glomerular filtration rate (52 +/- 18 vs. 212 +/- 23 microl/min, P < 0.01) and renal blood flow (0.58 +/- 0.08 vs. 0.85 +/- 0.06 ml/min, P < 0.01) in sham-operated mice. The decrement in glomerular filtration rate during endotoxemia was significantly attenuated in mice with denervated kidneys (32 vs. 79%). Moreover, there was no change in renal blood flow during endotoxemia in mice with renal denervation. The present results therefore demonstrate a protective role of renal denervation during normotensive endotoxemia-related ARF in mice, an effect that may be, at least in part, due to a diminished activation of the renin-angiotensin system.
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Affiliation(s)
- Wei Wang
- Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
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