ABSTRACT
<p><b>BACKGROUND</b>With the increase in hemodialysis (HD) patients, the blood dialysis patient's quality of life (QoL) and long-term survival are still a challenge for clinicians. Recent studies have found that most of the HD patients have sleep disorders, which have a certain correlation with long-term survival and QoL. But there are few studies of Chinese in this field. This study aimed to investigate whether increasing the dialysis dose can improve sleep quality, so we treated HD patients on long intermittent hemodialysis (LIHD).</p><p><b>METHODS</b>Forty patients who were treated by conventional HD at the Beijing Friendship Hospital Blood Purification Center were offered the option of LIHD. The patients' laboratory data, medication use, and questionnaire answers were analyzed. Conventional HD was delivered thrice weekly with 4 hours per treatment, and LIHD was delivered thrice weekly with 8 hours per treatment. The study lasted 6 months. Questionnaires included sleep quality survey and QoL SF-36; the former includes the Athens Insomnia Scale, Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS).</p><p><b>RESULTS</b>After conversion to LIHD the dialysis efficiency (Kt/V) significantly increased than before (P < 0.05) and clearance rate of urea nitrogen also increased from 67 to 78% (P < 0.01). After conversion, median values for Hb increased from 108.95 to 126.55 g/L (P < 0.01); albumin increased from 38.85 to 40.05 g/L (P < 0.01). Phosphorus decreased from 2.69 to 1.54 mmol/L (P < 0.01), but there was no alteration in blood calcium; phosphorus and calcium-phosphate product levels were under more control, but parathyroid hormone (iPTH) level did not change after conversion to LIHD. After conversion, blood pressure (BP) was better controlled than before and the mean number of antihypertensive drugs prescribed declined from 2.9 to 0.5 (P < 0.01). There was a significant reduction in the use of erythropoietin-stimulating agent of 5250 U/w (P < 0.01). Sleep quality significantly improved in the 2 months after conversion to LIHD, and the PSQI score decreased from 10.80 to 5.45 and the ESS score decreased from 12.05 to 5.30 (P < 0.01). However, sleep quality started to decline after 2 months on LIHD. QoL SF-36 score increased from 410.92 to 592.53 (P < 0.01).</p><p><b>CONCLUSION</b>LIHD offers an effective improvement in dialysis adequacy for Chinese maintenance HD patients, but it improves sleep quality only briefly which may be related to loss of serum calcium and parathyroid dysfunction.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Calcium , Blood , Kidney Failure, Chronic , Blood , Therapeutics , Phosphorus , Blood , Quality of Life , Renal Dialysis , Reference StandardsABSTRACT
<p><b>BACKGROUND</b>Numerous studies have shown that reducing the level of tumor necrosis factor-alpha (TNFα) through the use of anti-TNF antibodies or soluble TNF receptor is a safe and efficacious treatment to inflammatory diseases such as rheumatoid arthritis. Therefore, novel approaches to achieve this outcome are desired. The aim of this study was to investigate the characterization of a small molecule inhibitor, Y316, which blocks TNF mRNA upregulation and TNF production by lipopolysaccharides (LPS) stimulated monocytes.</p><p><b>METHODS</b>Peripheral blood mononuclear cells (PBMC) from healthy volunteers were plated in 24-well plates and stimulated with LPS (1 µg/ml), phorbol-12-myristate-13-acetate (PMA) (100 ng/ml), zymosan (10 µg/ml) and Tsst (100 ng/ml). Supernatants were collected after 4-hour culture at 37°C, and quantitative determination of TNFα, interleukin-1β (IL-1β), IL-6, IL-8, IL-10 and IL-2 production in the supernatants was performed by colorimetric enzyme-linked immunosorbent assay (ELISA). Total RNA of PBMC was isolated and cytokine mRNA quantitation was performed by using a RNA level measuring kit (R & D Systems). PBMC were pretreated with Y316 (10 µmol/L, 1 µmol/L, 0.1 µmol/L, 0.01 µol/L and 0.001 µmol/L) or dimethyl sulfoxide at 37°C for 10 minutes, and then stimulated with LPS or PMA, protein concentrations of p44.42, IKBα, P38 and Jun NH2-terminal kinase were determined by Western blotting. Cyclic adenosine-3',5'-monophosphate (cAMP) of PBMC was measured by enzyme immunoassay kit (Amersham Pharmacia Biotech).</p><p><b>RESULTS</b>Y316 blocked TNF production and inhibited the upregulation of TNF mRNA levels in response to LPS, and also prevented the production of IL-1 and IL-6. In contrast, Y316 augmented the production of IL-10 in LPS-stimulated monocytes. Y316 failed to prevent the production of IL-2 and TNF in antigen-stimulated T cells, suggesting that its effects may be cell-type specific. Y316 prevented the phosphorylation and activation of the MAPK, ERK, and therefore appeared to mediate its effects on TNF by acting at an early point in the signaling cascade induced in response to LPS. There was no effect of Y316 on cAMP levels either alone or in the presence of LPS.</p><p><b>CONCLUSIONS</b>Y316 appears to be a small molecule inhibiting TNF production, which may act via a novel mechanism. Identification of the target of Y316 may lead to the development of alternative strategies for achieving selective cytokine inhibition.</p>