Chronic kidney disease (CKD) is characterized by loss of renal function and a consequent increase of serum uremic toxins, which contribute to inflammation status. Deficiency of 25-vitamin D, often found in patients with CKD, has been included as an inflammatory factor since it might modulate the immune system. The aim of this study was to investigate the role of 25-vitamin D on inflammatory pathways in healthy and uremic environment. Toll-like receptor 4 (TLR4), oxidative stress (ROS), vitamin D receptor (VDR), 1-α hydroxylase (CYP27), 24 hydroxylase, cathelicidin, and MCP-1 were evaluated in monocytes exposed to a uremic serum pool compared with healthy pool. The human monocytes lineage (U937) was incubated with or without 25-vitamin D (50 ng/ml for 24 hours). TRL4, VDR, CYP27, CYP24, and ROS were evaluated by flow cytometry. We used ELISA to measure IL-6, TNF-α, IL-10, cathelicidin, and MCP-1 in the cell culture supernatant. We observed a higher expression of TRL-4, IL-6, TNF-α, IL-10, cathelicidin and MCP-1 in monocytes incubated with uremic serum when compared with serum from healthy individuals. Supplementation of 25-vitamin D was able to reduce the expression of TRL4, cathelicidin, and MCP-1 in the uremic environment. There was no difference in the expression of VDR, CYP27 and CYP24 intracellular enzymes. This in vitro study showed that the uremic pool activates inflammatory response in monocytes, which was reversed by 25-vitamin D supplementation; this finding suggests that 25-vitamin D has an anti-inflammatory role in the uremic environment. Chronic Kidney disease (CKD) is characterized by the loss of glomerular filtration rate resulting in serum accumulation of toxic substances, called uremic toxins 1. The accumulation of these compounds is defined as the uremic environment. It has been shown that uremic toxins are capable to induce an inflammatory response in patients with CKD 2-4. Uremic toxins can cause oxidative stress and stimulate the production of proinflammatory cytokines in this population. Several studies have been reported a relationship between uremic toxins (mainly indoxyl sulfate, p-cresyl sulfate, and indole-3-acetic acid) and inflammation 3,5,6. The indoxyl sulfate has been described to activate NF-ĸB, NADPH oxidase, upregulated mRNA and expression of intercellular adhesion molecule-1 (ICAM-1) 7-9 , and is also capable to induce endothelial injury with the formation of microvesicles that contribute to endothelial cell progenitors dysfunction 10. The p-cresyl sulfate and indole-3-acetic acid are associated with increased IL-6 and CRP, respectively, in patients with CKD 3,11. When renal function deteriorates to <15 ml/min/1,73 m 2 , patients usually need dialysis support. However, despite the technological advances in the dialysis procedures, thrice weekly conventional hemodialysis is not able to remove all toxins, particularly those too large and/or protein-bounded 12. Therefore, patients on dialysis still have serum circulating uremic toxins. Some studies have demonstrated a direct relati...

Anemia is a common complication that is associated with mortality in patients with chronic kidney disease (CKD). Despite the use of erythropoiesis-stimulating agents (ESAs) to correct anemia, some patients are hyporesponsive due to the state of micro-inflammation caused by uremic toxins and hepcidin, a hormone that plays a central role in iron homeostasis. Hemodiafiltration (OL-HDF) has been associated with better clearance of uremic toxins, such as indoxyl sulfate (IS), p-cresyl sulfate (PCS) and indole acetic ascorbic (IAA) than conventional hemodialysis (HD). The aim of the study was to evaluate the effect of OL-HDF treatment on the concentration of IS, PCS, IAA, hepcidin and inflammatory biomarkers in CKD patients. Thirty-one patients (> 65 years old) incident in OL-HDF were followed for 6 months. IS, PCS, IAA, biochemical parameters, hepcidin and inflammatory cytokines were evaluated at baseline and after 6 months. We observed a significant decrease in IS and CRP plasma concentration, an increase in hemoglobin and hematocrit after 6 months of treatment with OL-HDF (p <0.05). This prospective observational study demonstrated that OL-HDF was capable to reduce IS and CRP in older patients. Whether this reduction may have an impact on clinical outcomes must be investigated in a future study.

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IntroductionSarcopenia is a syndrome characterized by progressive loss of skeletal muscle mass, decreased strength, decreased physical performance, increased risk of falls, fractures, hospitalization, and mortality. In patients with chronic renal disease on dialysis (CKD) approximately 40% present sarcopenia due to the effect of toxic substances that are not excreted and induce activation of the inflammatory response that contributes to muscle catabolism, mitochondrial alterations, decrease of satellite cells, changes hormones and loss of neuromuscular junctions. Sarcopenia is well documented in patients with CKD, where the diagnosis is made by measuring the skeletal muscle index, measuring the strength of the wrist and low speed in walking.However, in patients with acute kidney injury (AKI) who abruptly lose kidney function; sarcopenia has not yet been investigated. In addition, because these are hospitalized in intensive care units, the classic characterization of sarcopenia by measuring skeletal muscle mass is not possible; requiring the use of serum biomarkers that represent the loss of muscle mass.ObjectiveObjective of this study was to investigate sarcopenia through serum markers of muscle mass loss in AKI patients.Material and MethodsWe included 77 severe patients without AKI and 83 severe AKI patients all admitted to the Intensive Care Unit. Patients with AKI were characterized by AKIN criteria that used a 0.3 mg/dL increase in serum creatinine within seven days of admission in the hospital. Serum markers of sarcopenia: growth factor like insulin‐1 (IGF‐1), myostatin, interleukin‐6 (IL‐6), tumor necrosis factor alpha (TNF‐α) and interleukin‐15 (IL‐15) were studied by enzyme‐linked immunosorbent assay (ELISA). Results are expressed as median. Mann‐Whitney test was used to analyze the groups.ResultsAll AKI patients presented serum creatinine> 3.1 mg/dL (reference value 0.8 – 1.3 mg/dL). We observed increased serum IL‐6 (pg/mL) levels [AKI 21 (11 – 32) vs. No‐AKI 12 (7–19); p <0.001], TNF‐α (pg/mL) [AKI 8.2 (6.7 – 10.5) vs. No‐AKI 7.0 (6.2–7.9); p <0.001], IL‐10 (pg/mL) [AKI 1.1 (0.8 – 1.6) vs. No‐AKI 0.8 (0.7 – 1.0); p <0.001], and IL‐15 (pg/mL) [AKI 5.8 (3.3 – 7.7) vs. No‐AKI 4.5 (2.8 – 6.1); p = 0.04] and we did not observe differences in IGF‐1 (ng/mL) [AKI 0.3 (0.1 – 0.5) vs. No‐AKI 0.3 (0.2 – 0.4); p = 0.53] and myostatin (ng/mL) [AKI 33 (19 – 57) vs. No‐AKI 37 (20–59); p = 0.30].ConclusionAKI patients presented higher inflammation characterized by increased serum levels of IL‐6, TNF‐α and IL‐15, which may contribute to sarcopenia. However, myostatin and IGF‐1 did not behave as a marker of muscle loss in this population studied.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

individuals, 18-63 years of age, with at least 18 months of continuous eligibility and a primary care or emergency department visit for LBP. Baseline covariates were captured in in the six-month period prior to their initial LBP diagnosis (index date) and opioid use was captured in the 12-month follow up period. Long-term opioid use was defined as at least 90 days of opioid use. PT and chiropractic were assessed in the 30-day period after index date. Multivariable logistic regression models were estimated to explore the influence of PT and chiropractic care adjusted for patient demographics and comorbidities. Results: 40,929 individuals met inclusion/exclusion criteria. Average age was 41 years, 64.5% were female and 79.9% had commercial health insurance coverage. PT and chiropractic care was used by 5.4% and 5.9% of the sample, respectively. Any opioid use after LBP diagnosis was observed in 54.3% of subjects, 4.4% used opioids long-term. PT was not associated with any opioid use (OR: 1.07; 95% CI: 0.98-1.18) or long-term opioid use (OR: 1.19; 95% CI: 0.97-1.45). Persons who received chiropractic care were less likely to be prescribed an opioid (OR: 0.88; 95% CI: 0.80-0.97) or to use opioids long-term (OR: 0.56; 95% CI: 040-0.77). Conclusions: Utilization of PT or chiropractic care in early management of back pain was low. Chiropractic care but not PT was associated with a lower likelihood of opioid use and long term opioid use.