Predialysis hypernatremia is a prognostic marker in acute kidney injury in need of renal replacement therapy.

BACKGROUND AND OBJECTIVES: The present study aimed to evaluate the prognostic impact of predialysis dysnatremia in patients with acute kidney injury requiring renal replacement therapy (RRT). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: A secondary analysis of a prospective multicenter cohort study was performed. Serum sodium (Na) concentrations were categorized immediately before the first RRT as normonatremia (135≤Na ≤145mEq/L), hyponatremia (mild [130≤Na ≤134mEq/L] or severe [Na ≤129mEq/L]), and hypernatremia (mild [146≤Na ≤155mEq/L] or severe [Na ≥156mEq/L]). Multivariable logistic regression was used to estimate the impact of sodium levels categories on hospital mortality. RESULTS: Dysnatremia occurred in 47.3% of 772 included patients. Hypernatremia was more frequent than hyponatremia (33.7% vs 13.6%, P=.001). Intensive care unit (ICU) and hospital mortality rates were 64.6% and 69%, respectively. Hospital mortality was higher in severe hypernatremia (89.1% [95% confidence interval {CI}, 78.7%-95.8%] vs 64.6% [CI, 59.8%-69.2%], P<.001, in normonatremia). Older patients, clinical admission, number of comorbidities, length of ICU stay before the beginning of RRT, and the number of organ dysfunctions were associated with higher hospital mortality. In multivariate analysis, severe hypernatremia (odds ratio, 2.87; 95% CI, 1.2-6.9), poor chronic heath status, severity of illness, sepsis, and lactate were independently associated with outcome. CONCLUSION: Almost 50% of patients with acute kidney injury in need of RRT in the ICU had mild or severe dysnatremia before dialysis initiation. Hypernatremia was the main sodium disturbance and independently associated with poor outcome in the study population.

Evaluation of immunoprotective activity of six leptospiral proteins in the hamster model of leptospirosis.

Leptospirosis is a worldwide zoonosis caused by pathogenic Leptospira. The whole-genome sequence of L. interrogans serovar Copenhageni together with bioinformatics tools represent a great opportunity to search for novel antigen candidates that could be used as subunit vaccine against leptospirosis. We focused on six genes encoding for conserved hypothetical proteins predicted to be exported to the outer membrane. The genes were amplified by PCR from Leptospira interrogans genomic DNA and were cloned and expressed in Escherichia coli. The recombinant proteins tagged with N-terminal hexahistidine were purified by metal-charged chromatography. The immunization of hamsters followed by challenge with lethal dose of virulent strain of Leptospira showed that the recombinant proteins Lsa21, Lsa66 and rLIC11030 elicited partial protection to animals. These proteins could be used combined or in a mixture with novel adjuvants in order to improve their effectiveness.

Plasminogen binding proteins and plasmin generation on the surface of Leptospira spp.: the contribution to the bacteria-host interactions.

Leptospirosis is considered a neglected infectious disease of human and veterinary concern. Although extensive investigations on host-pathogen interactions have been pursued by several research groups, mechanisms of infection, invasion and persistence of pathogenic Leptospira spp. remain to be elucidated. We have reported the ability of leptospires to bind human plasminogen (PLG) and to generate enzimatically active plasmin (PLA) on the bacteria surface. PLA-coated Leptospira can degrade immobilized ECM molecules, an activity with implications in host tissue penetration. Moreover, we have identified and characterized several proteins that may act as PLG-binding receptors, each of them competent to generate active plasmin. The PLA activity associated to the outer surface of Leptospira could hamper the host immune attack by conferring the bacteria some benefit during infection. The PLA-coated leptospires obstruct complement C3b and IgG depositions on the bacterial surface, most probably through degradation. The decrease of leptospiral opsonization might be an important aspect of the immune evasion strategy. We believe that the presence of PLA on the leptospiral surface may (i) facilitate host tissue penetration, (ii) help the bacteria to evade the immune system and, as a consequence, (iii) permit Leptospira to reach secondary sites of infection.