Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients

Background

Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting.

Methods

The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained.

Results

Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased.

Conclusions

In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage.

     

Value of the tuberculin skin testing and of an interferon-gamma release assay in haemodialysis patients after exposure to M. tuberculosis

ABSTRACT: BACKGROUND: Patients with end-stage renal disease (ESRD) and Mycobacterium tuberculosis infection pose a high risk of developing active TB disease. It is therefore important to detect latent TB infection (LTBI) to be able to offer treatment and prevent progression to TB disease. We assessed the value of the tuberculin skin test (TST) and of an interferon-gamma release assay (Quantiferon[REGISTERED SIGN]-TB Gold in-Tube, QFT) for diagnosing LTBI in ESRD patients, after prolonged exposure to a highly contagious TB case in a haemodialysis unit. As a high number of patients presented erythema without induration in the TST response, this type of reaction was also analysed. METHOD: The TST and QFT were simultaneously performed twelve weeks after the last possible exposure to a bacilliferous TB patient. If the first TST (TST-1) was negative, a second TST (TST-2) was performed 15 days later to detect a booster response. A comparison was made between the TST responses (including those cases with erythema without induration) and those for the QFT. The correlation with risk of infection and the concordance between tests were both analysed. RESULTS: A total of 52 patients fulfilled the inclusion criteria. Overall, 11 patients (21.2%) had a positive TST response: 3 for TST-1 and 8 for TST-2, and 18 patients (34.6%) showed a positive QFT response (p = 0.065). Erythema without induration was found in 3 patients at TST-1 and in a further 9 patients at TST-2. The three patients with erythema without induration in TST-1 had a positive TST-2 response. Concordance between TST and QFT was weak for TST-1 (kappa = 0.21); it was moderate for overall TST (kappa = 0.49); and it was strong if both induration and erythema (kappa = 0.67) were considered. CONCLUSIONS: In patients with ESRD, erythema without induration in the TST response could potentially be an indicator of M. tuberculosis infection. The QFT shows better accuracy for LTBI diagnosis than the TST.     

Synergistic effect of two combinations of antituberculous drugs against Mycobacterium tuberculosis

Fluoroquinolones such as ofloxacin are promising drugs to treat drug-resistant tuberculosis (TB) and have been proposed for shortening the treatment of TB. The objectives were to study the synergistic effect of the combinations of three drugs and to evaluate the in?vitro interactions of the following combinations against Mycobacterium tuberculosis: A) isoniazid, rifampicin, and ethambutol and B) ofloxacin, rifampicin, and ethambutol using an adaptation of the two-dimensional chequerboard assay. A total of 12 isolates resistant to isoniazid or to isoniazid-streptomycin and 11 drug-susceptible isolates were tested. The fractional inhibitory concentration (FICI) was calculated as follows: FICI?=?FIC(A)?+?FICB?+?FIC(C)?=?A/MIC(A)?+?B/MIC(B)?+?C/MIC(C) where A, B and C were the MICs of each antibiotic in combination and MIC(A), MIC(B) and MIC(C) were the individual MICs. The FICI was interpreted as synergism when the value was ≤0.75. In combination A, 11 drug-susceptible isolates decreased the individual MIC one to three dilutions, showing indifferent activity in 81.8% (FICI?=?0.88-1.6) and synergistic activity in 18.1% (FICI?=?0.6). In combination B, 21 out of the 23 isolates studied (91.3%) showed synergism (FICI?=?0.31-0.62). In conclusion, adaptation of the two-dimensional chequerboard assay is a reliable method to study in?vitro three-drug combinations. Both three-drug combinations tested may be useful against drug-resistant isolates, although the combination including ofloxacin showed better efficacy, being of potential use in drug-susceptible and isoniazid-resistant isolates.     

Impact of incident comorbidity on functional loss in elderly chronic kidney disease patients undergoing hemodialysis

The incidence of end stage renal disease in older persons has been increasing progressively over the last 10 years. Improved survival rates with renal replacement therapy are making this increased prevalence even more pronounced. The usual risks of morbidity and requirements for specialized care associated with older people increase dramatically when they have chronic kidney disease (CKD). It has been seen that the majority of patients in hemodialysis units are over the age of 60, and have significant co-morbidities. The relationship between older age, chronic disorders and functional dependence (FD) is well known. Accordingly, nursing care planning must be designed with this in mind. The aim of this study was to assess whether the comorbidity associated with CKD modifies FD in patients on hemodialysis. We undertook a prospective longitudinal cohort study of hemodialysis outpatients in Málaga, Spain, using the Barthel test to establish FD and the Charlson comorbidity index to quantify comorbidity. All health events were analyzed to select those study patients with incident comorbidity, understood as the appearance of a new disease that could modify the Charlson comorbidity index, and determine the change in FD. Multivariate linear regression showed that the best model for predicting functional loss was that which considered comorbidity adjusted for age, particularly when it occurred as a result of hospital admission, as it was shown to have an important predictive value for the onset of a decrease in functional dependency scores in patients with CKD.     

Impaired circadian variation of platelet activity in patients with sleep apnea

Background  

Cardiovascular diseases are frequent in patients with obstructive sleep apnea (OSAS). There is evidence that the day–night pattern of myocardial infarction and sudden cardiac death observed in the general population is altered in patients with OSAS. This study investigates potential abnormalities in the circadian profiles of platelet activity in OSAS.     

Assessment of the anterior scleral thickness in central serous chorioretinopathy patients by optical coherence tomography

Purpose

To assess the anterior scleral thickness (AST) and describe the presence of a visible supraciliary space (SCS) in central serous chorioretinopathy (CSC) patients by swept-source optical coherence tomography (SS-OCT).

Study design

Cross-sectional comparative study.

Material and Methods

Three groups were studied: 1) 64 eyes of 54 patients with CSC with persistent subretinal fluid (SRF); 2) 42 fellow eyes of CSC patients without SRF; 3) 65 eyes of 65 controls matched by age, sex and axial length (AL). The AST was measured in the temporal and nasal quadrants at 0, 1, and 2 mm from the scleral spur by SS-OCT. The presence of a visible SCS was also assessed.

Results

No differences were observed in the AST0 among the three groups (p≥ 0.665). The temporal AST1 was significantly thicker in the CSC group (530.3 ±67.1 µm) than in the controls (505.5 ±73.9; p=0.041). Mean AST2 was also thicker in the CSC group and the fellow eyes both for the temporal (519.4 ±89.1 µm and 519.8 ±98.5 µm respectively) and nasal quadrants (564.2 ±124.9 µm and 570.5 ±131.0 µm) than in the controls (450.1 ±76.8 and 473.3 ±111.6 µm) (all p≤0.001). A visible SCS was detected in the eyes of 8 CSC patients, in 4 fellow eyes and only in 1 control eye.

Conclusions

AST measured by SS-OCT was significantly greater in CSC eyes than in healthy eyes. Also, a visible SCS was detected in CSC eyes. Thus, thicker sclera in CSC eyes could be associated with the physiopathology of this disease.