Hypoalbuminemia: a risk factor for acute kidney injury development and progression to chronic kidney disease in critically ill patients.

PURPOSE: The increased likelihood of poor outcomes in critically ill patients with hypoalbuminemia is well recognized. However, hypoalbuminemia remains poorly defined as an independent predictor of acute kidney injury (AKI) and stage 4 chronic kidney diseases (CKD4). The aim of this study was to assess the role of hypoalbuminemia as an independent risk factor for AKI and CKD4 in critically ill patients. DESIGN: A retrospective cohort study. SETTING: General intensive care unit (ICU) at Anhui Provincial Hospital, PR China. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We screened patients admitted to the ICU at Anhui Provincial Hospital between January 1, 2008, and October 31, 2011, and included those aged >18 years with available records of serum albumin (SA), baseline serum creatinine, and outcome data. The exclusion criteria were: (1) patients with known AKI and CKD stage 4, 5 before ICU admission; (2) patients lost to follow-up; and (3) patients without research authorization. A total of 588 patients with available data were enrolled in the study, and 62 patients with preexisting CKD stage 4 and CKD stage 5 and 115 with preexisting AKI were excluded. Thirty patients were lost to follow-up. Ultimately, 381 patients were analyzed, 233 (61.2%) of whom developed AKI. Patients with low SA were significantly more likely than those with normal SA (p = 0.0003) to develop AKI, and to progress from AKI to CKD4 (p = 0.0229). More patients in the AKI group than in the non-AKI group had risk factors such as hypotension, mechanical ventilation (MV), proteinuria, sepsis, nephrotoxin exposure, and high-risk surgery (p < 0.01). The difference in duration of MV, ICU days, ICU mortality, hospital days, and hospital mortality between the AKI and non-AKI groups was also significant (p < 0.01). Logistic regression showed that hypoalbuminemia was significantly associated with AKI and CKD4 [odds ratio (OR) 1.810, 95% confidence interval (CI) 1.102-2.992, and OR 2.494, 95% CI 1.231-5.295, respectively]. After 4 years of follow-up, Kaplan-Meier analysis showed that survival in hypoalbuminemia patients was significantly shorter than in patients with normal SA (p = 0.0393). In the Cox proportional hazard model, hypoalbuminemia was an independent predictor of long-term mortality (hazard ratio 1.5, 95% CI 1.042-2.183, p = 0.0291). CONCLUSION: Hypoalbuminemia in critically ill patients is independently associated with an increased risk of development of AKI and AKI progressing to CKD4.

Hyperinsulinemia adversely affects lung structure and function.

There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 µg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of ß-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of ß-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.

Targeting bacterial biofilms via surface engineering of gold nanoparticles.

Bacterial biofilms are associated with persistent infections that are resistant to conventional antibiotics and substantially complicate patient care. Surface engineered nanoparticles represent a novel, unconventional approach for disruption of biofilms and targeting of bacterial pathogens. Herein, we describe the role of surface charge of gold nanoparticles (AuNPs) on biofilm disruption and bactericidal activity towards Staphylococcus aureus and Pseudomonas aeruginosa which are important ventilator associated pneumonia (VAP) pathogens. In addition, we study the toxicity of charged AuNPs on human bronchial epithelial cells. While 100% positively charged AuNP surface was uniformly toxic to both bacteria and epithelial cells, reducing the extent of positive charge on the AuNP surface at moderate concentrations prevented epithelial cell toxicity. Reducing surface charge was however also less effective in killing bacteria. Conversely, increasing AuNP concentration while maintaining a low level of positivity continued to be bactericidal and disrupt the bacterial biofilm and was less cytotoxic to epithelial cells. These initial in vitro studies suggest that modulation of AuNP surface charge could be used to balance effects on bacteria vs. airway cells in the context of VAP, but the therapeutic window in terms of concentration vs. surface positive charge may be limited. Additional factors such as hydrophobicity may need to be considered in order to design AuNPs with specific, beneficial effects on bacterial pathogens and their biofilms.