Novel kidney injury biomarkers in a large cohort of children with sickle cell anemia.

Aim: The aim of this study was to compare novel kidney injury biomarkers in sickle cell anemia (SCA) children with and without albuminuria or glomerular hyperfiltration. Materials & methods: A total of 358 Brazilian children with SCA were studied. Fifteen kidney injury biomarkers in urine were measured. Albuminuria was defined as urine albumin/creatinine ratio >100 mg/g. Glomerular hyperfiltration was defined as estimated glomerular filtration rate ≥140 ml/min/1.73 m2. Results: After adjustment for age, sex and modifying therapies in use, EGF and collagen IV urinary levels were associated with albuminuria. Renin and clusterin levels were associated with hyperfiltration. Conclusion: Levels of novel kidney injury biomarkers were associated with albuminuria and hyperfiltration in Brazilian children with SCA, suggesting concomitant structural and functional abnormalities.

Biomarkers in vesicoureteral reflux: an overview.

Aim: This article aimed to review the role of cytokines, chemokines, growth factors and cellular adhesion molecules as biomarkers for vesicoureteral reflux (VUR) and reflux nephropathy (RN). Methods: We reviewed articles from 1979 onward by searching PubMed and Scopus utilizing the combination of words: 'VUR' or 'RN' and each one of the biomarkers. Results: Genetic, inflammatory, fibrogenic, environmental and epigenetic factors responsible for renal scarring need to be better understood. TGF-ß, IL-10, IL-6, IL-8 and TNF seem to exert a role in VUR particularly in RN based on the current literature. Serum levels of procalcitonin have been also associated with high-grade VUR and RN. These molecules should be more intensively evaluated as potential biomarkers for renal scarring in VUR. Conclusion: Further studies are necessary to define which molecules will really be of utility in clinical decisions and as therapeutic targets for VUR and RN.

Differences in the immune-inflammatory profiles of unipolar and bipolar depression.

BACKGROUND: Major depressive disorder (MDD) and bipolar depression (BD) both share increased immune-inflammatory activation. However, there are unclear patterns of differences in peripheral immune profiles between them. METHODS: We examined such differences in 245 MDD and 59 BD patients, recruited in the same center, who were in an acute depressive episode of moderate severity. Hierarchical binary logistic regression analyses and generalized linear models were used to compare levels of plasma biomarkers between groups and to predict dichotomous classification. RESULTS: Interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1, IL-12 and IL-10 were significantly higher in MDD than in BD, whereas IL-6, sTNFR2, IL-18, IL-33, ST2 (IL1R Like 1) and KLOTHO were significantly higher in BD than in MDD. Moreover, logistic regression analyses correctly classified BD and MDD patients with 98.1% accuracy, using a combination of IL-6, IL-8, ST2, sTNFR2 (directly associated with BD) and IL-12 and TNF-α (directly associated with MDD). Patients with MDD with melancholic features showed higher IL-1ß levels than those without melancholia. The sTNFR1 / sTNFR2 ratio significantly predicted MDD and state and trait anxiety and negative affect. Results remained significant after covariate adjustment, including drug use. LIMITATIONS: Cross-sectional study. Lack of control comparison group. Differences in exposure to medications among participants. CONCLUSIONS: Differences in immune profiles between BD and MDD patients exist, especially for the compensatory immune-regulatory system (CIRS): increased IL-10 is the primary immune-regulatory mechanism in MDD, while increased sTNFR2 and KLOTHO are the primary regulatory mechanisms in BD.

Cytokines plasma levels during antidepressant treatment with sertraline and transcranial direct current stimulation (tDCS): results from a factorial, randomized, controlled trial.

RATIONALE: The inflammatory hypothesis of depression states that increased levels of pro-inflammatory cytokines triggered by external and internal stressors are correlated to the acute depressive state. This hypothesis also suggests that pharmacotherapy partly acts in depression through anti-inflammatory effects. Transcranial direct current stimulation (tDCS) is a novel, promising, non-invasive somatic treatment for depression, although its antidepressant mechanisms are only partly understood. OBJECTIVES: We explored the effects of tDCS and sertraline over the immune system during an antidepressant treatment trial. METHODS: In a 6-week, double-blind, placebo-controlled trial, 73 antidepressant-free patients with unipolar depression were randomized to active/sham tDCS and sertraline/placebo (2 × 2 design). Plasma levels of several cytokines (IL-2, IL-4, IL-6, IL-10, IL-17a, IFN-γ, and TNF-α) were determined to investigate the effects of the interventions and of clinical response on them. RESULTS: All cytokines, except TNF-α, decreased over time, these effects being similar across the different intervention-groups and in responders vs. non-responders. CONCLUSIONS: tDCS and sertraline (separately and combined) acute antidepressant effects might not specifically involve normalization of the immune system. In addition, being one of the first placebo-controlled trials measuring cytokines over an antidepressant treatment course, our study showed that the decrease in cytokine levels during the acute depressive episode could involve a placebo effect, highlighting the need of further placebo-controlled trials and observational studies examining cytokine changes during depression treatment and also after remission of the acute depressive episode.