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Soluble Urokinase Receptor and Acute Kidney Injury.
Hayek, Salim S; Leaf, David E; Samman Tahhan, Ayman; Raad, Mohamad; Sharma, Shreyak; Waikar, Sushrut S; Sever, Sanja; Camacho, Alex; Wang, Xuexiang; Dande, Ranadheer R; Ibrahim, Nasrien E; Baron, Rebecca M; Altintas, Mehmet M; Wei, Changli; Sheikh-Hamad, David; Pan, Jenny S-C; Holliday, Michael W; Januzzi, James L; Weisbord, Steven D; Quyyumi, Arshed A; Reiser, Jochen.
Afiliação
  • Hayek SS; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Leaf DE; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Samman Tahhan A; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Raad M; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Sharma S; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Waikar SS; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Sever S; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Camacho A; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Wang X; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Dande RR; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Ibrahim NE; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Baron RM; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Altintas MM; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Wei C; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Sheikh-Hamad D; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Pan JS; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Holliday MW; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Januzzi JL; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Weisbord SD; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Quyyumi AA; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
  • Reiser J; From the Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor (S.S.H.); the Divisions of Renal Medicine (D.E.L., S. Sharma, S.S.W.) and Pulmonary and Critical Care Medicine (R.M.B.), Brigham and Women's Hospital, the Section of Nephrology, Department of Medicine, Boston
N Engl J Med ; 382(5): 416-426, 2020 01 30.
Article em En | MEDLINE | ID: mdl-31995687
BACKGROUND: Acute kidney injury is common, with a major effect on morbidity and health care utilization. Soluble urokinase plasminogen activator receptor (suPAR) is a signaling glycoprotein thought to be involved in the pathogenesis of kidney disease. We investigated whether a high level of suPAR predisposed patients to acute kidney injury in multiple clinical contexts, and we used experimental models to identify mechanisms by which suPAR acts and to assess it as a therapeutic target. METHODS: We measured plasma levels of suPAR preprocedurally in patients who underwent coronary angiography and patients who underwent cardiac surgery and at the time of admission to the intensive care unit in critically ill patients. We assessed the risk of acute kidney injury at 7 days as the primary outcome and acute kidney injury or death at 90 days as a secondary outcome, according to quartile of suPAR level. In experimental studies, we used a monoclonal antibody to urokinase plasminogen activator receptor (uPAR) as a therapeutic strategy to attenuate acute kidney injury in transgenic mice receiving contrast material. We also assessed cellular bioenergetics and generation of reactive oxygen species in human kidney proximal tubular (HK-2) cells that were exposed to recombinant suPAR. RESULTS: The suPAR level was assessed in 3827 patients who were undergoing coronary angiography, 250 who were undergoing cardiac surgery, and 692 who were critically ill. Acute kidney injury developed in 318 patients (8%) who had undergone coronary angiography. The highest suPAR quartile (vs. the lowest) had an adjusted odds ratio of 2.66 (95% confidence interval [CI], 1.77 to 3.99) for acute kidney injury and 2.29 (95% CI, 1.71 to 3.06) for acute kidney injury or death at 90 days. Findings were similar in the surgical and critically ill cohorts. The suPAR-overexpressing mice that were given contrast material had greater functional and histologic evidence of acute kidney injury than wild-type mice. The suPAR-treated HK-2 cells showed heightened energetic demand and mitochondrial superoxide generation. Pretreatment with a uPAR monoclonal antibody attenuated kidney injury in suPAR-overexpressing mice and normalized bioenergetic changes in HK-2 cells. CONCLUSIONS: High suPAR levels were associated with acute kidney injury in various clinical and experimental contexts. (Funded by the National Institutes of Health and others.).
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ativador de Plasminogênio Tipo Uroquinase / Angiografia Coronária / Receptores de Ativador de Plasminogênio Tipo Uroquinase / Injúria Renal Aguda / Procedimentos Cirúrgicos Cardíacos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ativador de Plasminogênio Tipo Uroquinase / Angiografia Coronária / Receptores de Ativador de Plasminogênio Tipo Uroquinase / Injúria Renal Aguda / Procedimentos Cirúrgicos Cardíacos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article