Reversal of Acute Kidney Injury-Induced Neutrophil Dysfunction: A Critical Role for Resistin.

OBJECTIVES: To assess the reversibility of acute kidney injury-induced neutrophil dysfunction and to identify involved mechanisms. DESIGN: Controlled laboratory experiment and prospective observational clinical study. SETTING: University laboratory and hospital. SUBJECTS: C57BL/6 wild-type mice. PATIENTS: Patients with septic shock with or without acute kidney injury. INTERVENTIONS: Murine acute kidney injury was induced by intraperitoneal injections of folic acid (nephrotoxic acute kidney injury) or by IM injections of glycerol (rhabdomyolysis-induced acute kidney injury). After 24 hours, we incubated isolated neutrophils for 3 hours in normal mouse serum or minimum essential medium buffer. We further studied the effects of plasma samples from 13 patients with septic shock (with or without severe acute kidney injury) on neutrophilic-differentiated NB4 cells. MEASUREMENTS AND MAIN RESULTS: Experimental acute kidney injury significantly inhibited neutrophil migration and intracellular actin polymerization. Plasma levels of resistin, a proinflammatory cytokine and uremic toxin, were significantly elevated during both forms of acute kidney injury. Incubation in serum or minimum essential medium buffer restored normal neutrophil function. Resistin by itself was able to induce acute kidney injury-like neutrophil dysfunction in vitro. Plasma resistin was significantly higher in patients with septic shock with acute kidney injury compared with patients with septic shock alone. Compared with plasma from patients with septic shock, plasma from patients with septic shock and acute kidney injury inhibited neutrophilic-differentiated NB4 cell migration. Even after 4 days of renal replacement therapy, plasma from patients with septic shock plus acute kidney injury still showed elevated resistin levels and inhibited neutrophilic-differentiated NB4 cell migration. Resistin inhibited neutrophilic-differentiated NB4 cell migration and intracellular actin polymerization at concentrations seen during acute kidney injury, but not at normal physiologic concentrations. CONCLUSIONS: Acute kidney injury-induced neutrophil dysfunction is reversible in vitro. However, standard renal replacement therapy does not correct this defect in patients with septic shock and acute kidney injury. Resistin is greatly elevated during acute kidney injury, even with ongoing renal replacement therapy, and is sufficient to cause acute kidney injury-like neutrophil dysfunction by itself.

The development of a feeding, swallowing and oral care program using the PRECEDE-PROCEED model in an orphanage-hospital in Guatemala.

PURPOSE: The purpose of this study was to evaluate a long-term on-going international academic service-learning (I-ASL) intervention. Its goal was to improve swallowing, feeding and oral care technique of medical staff in an orphanage in Guatemala to children who are medically complex and have special needs. METHOD: The PRECEDE-PROCEED model was used as the conceptual framework of the program. Five major target areas were identified during the diagnosis, assessment, implementation and evaluation phases of the model: knowledge and skills, feeding equipment, feeding and oral care technique, positioning and communication. Verbal instruction, modelling and small group training was provided by the research team across all visits. A five-day intervention designed to increase feeders' knowledge of feeding and oral care technique, signs and symptoms and complications of dysphagia and to improve their feeding, positioning and oral care technique was implemented and evaluated. RESULT: Statistical analyses showed significant increases in knowledge and appropriate feeding, positioning and oral care technique. CONCLUSION: As a consequence of the intervention, a trusting and mutually supportive relationship was built between the I-ASL team and the host organization.