Restless legs syndrome in end stage renal disease patients undergoing hemodialysis.

BACKGROUND: The prevalence of Restless legs syndrome (RLS) in End Stage Renal Disease (ESRD) patients is higher than that in the general population. However, the associations of RLS within the ESRD population are inconsistent and RLS is usually neglected in dialysis centers, although it impairs the life quality among ESRD patients. We aim to investigate the prevalence of RLS in patients with ESRD undergoing maintenance hemodialysis and evaluate the risk factors of developing RLS and the effect of RLS on quality of life among ESRD patients. METHODS: ESRD patients undergoing maintenance hemodialysis in Shanghai General Hospital dialysis unit from July 2016 to October 2016 were enrolled in the study. RLS was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group (IRLSSG). IRLSSG Severity Scale was used to evaluate the severity of RLS. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and Hospital Anxiety and Depression Scale (HADS) was used to estimate anxiety and depression. Serologic and historic variables were analyzed to determine predictors of RLS in the ESRD population. RESULTS: A total of 137 ESRD patients were enrolled. The prevalence of RLS among the ESRD patients was 20.44%. The risk of RLS was increased significantly in females (OR = 2.729, p = 0.032) and daily alcohol drinkers (OR = 4.716, p = 0.022). RLS increased the risks of sleep disorders (25/28, 89.3% vs 73/109, 67.0%, p = 0.02) and sedative hypnotics intake (7/28, 25.0% vs 10/109, 9.2%, p = 0.047) and impaired the sleep quality (7/109 vs 11/28, p = 0.001) according to PSQI sum scores. CONCLUSION: A high RLS prevalence among the ESRD patients undergoing hemodialysis was confirmed. ESRD patients who are women and drinking alcohol have a higher risk of RLS. The sleep quality was significantly impaired and sleeping medication use was more common among the ESRD patients with RLS.

CKD autophagy activation and skeletal muscle atrophy-a preliminary study of mitophagy and inflammation.

BACKGROUND/OBJECTIVES: Long-lived proteins and organelles, such as mitochondria and the sarcoplasmic reticulum, are degraded by autophagy. However, the specific role of autophagy in chronic kidney disease (CKD) muscle atrophy is still undefined. SUBJECTS/METHODS: This was a cross-sectional study with 20 subjects and 11 controls. Autophagy induction was studied in human skeletal muscle biopsies from CKD patients and controls by comparing the cross-sectional areas of muscle fibers, protein, and mRNA expression of autophagy-related genes and the appearance of autophagosomes. RESULTS: The cross-sectional area of muscle fibers was decreased in CKD patients as compared with the control group. CKD was associated with activated autophagy and mitophagy, as measured by the elevated mRNA and protein expression of BNIP3, (microtubule-associated proteins 1 A/1B light chain 3, also MAP1LC3) LC3, p62, PINK1, and PARKIN in the skeletal muscle and isolated mitochondria of the CKD group. Electron microscopy and immunohistofluorescence analysis showed mitochondrial engulfment by autophagosomes. Mitophagy was further demonstrated by the colocalization of LC3 and p62 puncta with the mitochondrial outer membrane protein TOM20. In addition, degradative FOXO3 (Forkhead box O3) was activated and synthetic mTOR (mammalian target of rapamycin) was inhibited, whereas the upstream mediators VPS34 (class III PI3-kinase) and AKT (protein kinase B, PKB) were activated in CKD patients. CONCLUSIONS: Hyperactive autophagy and mitophagy may play important roles in CKD muscle atrophy. Autophagy was activated by FOXO3 translational factors in the skeletal muscle tissues of CKD patients, which maybe a new way of intervention for CKD muscle atrophy.

Phosphate stimulates myotube atrophy through autophagy activation: evidence of hyperphosphatemia contributing to skeletal muscle wasting in chronic kidney disease.

BACKGROUND: Accelerated muscle atrophy is associated with a three-fold increase in mortality in chronic kidney disease (CKD) patients. It is suggested that hyperphosphatemia might contribute to muscle wasting, but the underlying mechanisms remain unclear. Although evidence indicates that autophagy is involved in the maintenance of muscle homeostasis, it is not known if high phosphate levels can result in activation of autophagy, leading to muscle protein loss. METHODS: Immortalized rat L6 myotubes were exposed to a high concentration of phosphate, with or without autophagy inhibition. Myotube atrophy was examined by phase contrast microscopy. Autophagic activity was assessed by measuring the expression of microtubule-associated protein 1 light chain 3 (LC3) and p62 using quantitative real-time polymerase chain reaction and western blot. RESULTS: Phosphate induced cell atrophy in L6 myotubes in a dose- and time-dependent manner, and these responses were not associated with calcification or osteogenesis. Phosphate also dose- and time-dependently increased the LC3-II/LC3-I ratio. Inhibition of autophagy with wortmannin or knockdown of Atg5 significantly suppressed myotube atrophy caused by high phosphate concentration. CONCLUSIONS: High phosphate concentration induces muscle cell atrophy through the activation of autophagy. Targeting autophagy could be a therapeutic strategy for preventing muscle wasting caused by hyperphosphatemia.

Potassium metabolism in continuous ambulatory peritoneal dialysis patients.

BACKGROUND: Hypokalemia is common and may have contributed to the poor clinical outcome in peritoneal dialysis (PD) patients. In this study, we made a detailed investigation on the potassium metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients and tried to find out the possible factors associated with the high prevalence of hypokalemia in PD patients. METHODS: A cross-sectional survey in 243 clinically stable CAPD patients was made in our PD center in 2010. Patients were divided into four groups according to whether they were anuric or not and different dialysis regimens. Patients' demographic data and data on potassium metabolism including dietary potassium intakes, residual renal potassium, and peritoneal dialysis potassium removal were collected. RESULTS: The average potassium intake in our 243 PD patients was 32.1 ± 11.1 mmol/day. The total potassium removal was significantly higher in non-anuric patients as compared to anuric patients (33.2 ± 9.1 vs. 23.0 ± 4.7 mmol/day for 3 exchanges per day and 35.2 ± 8.9 vs. 28.6 ± 6.3 mmol/day for 4 exchanges per day, respectively, p < 0.01) and in anuric patients dialyzed with 4 exchanges per day as compared to anuric patients dialyzed with 3 exchanges per day (28.6 ± 6.3 vs. 23.0 ± 4.7 mmol/L, p < 0.05). Compared to non-anuric patients dialyzed with 3 exchanges per day, serum potassium level was significantly lower (4.1 ± 0.7 vs. 4.5 ± 0.7 mmol/L, p < 0.05) while the prevalence of hypokalemia was significantly higher (22.2% vs. 9.3%, p < 0.05) in non-anuric patients that dialyzed with 4 exchanges per day. There was a strong correlation between renal potassium removal and renal urea Kt/V (R(2) linear = 0.645, p < 0.05). In a linear multiregression analysis, dietary potassium intake, intracellular water (ICW) significantly positively predicted serum potassium level while dialysis exchanges, residual renal function (RRF), D/P potassium all significantly negatively predicted serum potassium levels. CONCLUSIONS: Our study suggested that if potassium intake was limited in PD patients, we should be aware of the risk of hypokalemia with high doses of PD when patients have good RRF. Our study also suggested that potassium removal in PD patients may not necessarily reflect potassium intake even if serum potassium is normal, the effect of ICW should be considered when evaluating potassium homeostasis.

[Measurement of dissolved organic nitrogen with nanofiltration pretreatment and its distribution characteristics in landscape water].

In this study, we present a nanofiltration (NF90, NF270) pretreatment to increase the precision of dissolved organic nitrogen (DON) measurements in water samples. The variations of DON measurements with and without NF pretreatment were investigated. And the effects on the removal of dissolved inorganic nitrogen (DIN) by NF90 and NF270 were compared. As shown in the results, the average removal rates reached 30.7%, 55.9% of NH4(+)-N, 50.0%, 73.1% of NO3(-) -N and 42.9%, 72.0% of NO2(-)-N for NF90 and NF270 pretreatment, respectively. NF270 was obviously more effective to remove the DIN species. Concentrations of DON measured using traditional methods varied from 0.09 to 0.46 mg x L(-1), with negative concentration (-0.08 mg x L(-1)) at site 2 and the DIN/TDN ratio ranged from 85.3% to 105%; while the concentrations of DON measurements varied from 0.03 to 0.58 mg x L(-1), and the DIN/TDN ratio ranged from 76.1% to 90.6% for NF90 pretreatment and varied from 0.10 to 0.59 mg x L(-1), and the DIN/TDN ratio ranged from 47.5% to 84.5% for NF270 pretreatment. The results indicated that nanofiltration pretreatment could effectively remove the DIN species, decrease the standard deviation of DON measurements and increase the precision of DON measurements. The distribution of DON in water samples of Beijing Olympic Forest Park was investigated. The results showed that there was seasonal variation in the concentrations of DON in landscape water from the Olympic Forest Park. And there was significant difference between the north and south part. The DON concentrations were less than 0.2 mg x L(-1) in November, March and May and higher in July in the north part, while the DON concentrations were lower in May and higher in November and March in the south part, ranging from 0.40-0.65 mg x L(-1).

Fibroblast growth factor-23 and interleukin-6 are risk factors for left ventricular hypertrophy in peritoneal dialysis patients.

BACKGROUND: Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular death in dialysis patients. Fibroblast growth factor-23 (FGF-23) and interleukin-6 (IL-6) were thought to be related to cardiovascular diseases (CVDs) in dialysis. METHODS: To determine the relationship between FGF-23, IL-6 and LVH in continuous ambulatory peritoneal dialysis (CAPD) patients, serum FGF-23 and IL-6 levels as well as standard laboratory parameters were assessed in 62 CAPD patients and 30 healthy controls. LVH was determined by echocardiography in dialysis patients. RESULTS: Serum FGF-23 and IL-6 levels were significantly higher in CAPD patients than in healthy controls, whereas both were higher in patients with LVH than in patients without LVH. FGF-23 was found to be positively associated with left ventricle mass index (LVMI) and serum phosphate. IL-6 level was positively associated with LVMI and negatively correlated with serum albumin and hemoglobin. Serum FGF-23 level was positively correlated with IL-6 level. CONCLUSION: FGF-23 and IL-6 are independent risk factors for LVH in CAPD patients and both collaborated in causing LVH in CAPD.

Lack of an association between a newly identified promoter polymorphism (-1702G > A) of the leukotriene C4 synthase gene and aspirin-intolerant asthma in a Korean population.

Aspirin-intolerant asthma (AIA) is a distinct clinical syndrome that refers to the development of bronchoconstriction in asthmatic individuals following the ingestion of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). It is widely recognized that increased cysteinyl leukotriene (cysLT) biosynthesis is associated with the development and progression of AIA. Leukotriene C4 synthase (LTC4S) is the terminal enzyme in cysLT production and is a strong candidate gene in the pathogenesis of aspirin-intolerant asthma (AIA). In this paper, we report a new single nucleotide polymorphism (SNP) of the LTC4S promoter, -1702G>A, in AIA patients and evaluate its genetic role in the association with the LTC4S-444 A>C polymorphism. We enrolled 110 AIA patients, 125 aspirin-tolerant asthma (ATA) patients, and 125 normal controls. SNP genotyping of the LTC4S-1702G>A and -444A>C polymorphisms was performed using SNP-IT assays. Haplotype analyses were performed using Haploview version 2.05, which is based on an estimation-maximization (EM) algorithm. There were no significant differences in the allele or genotype frequencies of the LTC4S-1702G>A and -444A>C polymorphisms among the three groups (p > 0.05), with no significant differences in the observed haplotype frequencies (p > 0.05). Moreover, no significant associations were found between the genotype of each SNP in AIA patients with the clinical characteristics, including a forced expiratory volume in one second (FEV1) %, a provocation concentration of methacholine to induce more than 20% decrease of FEV1 (PC20) to methacholine, and serum total IgE levels (p > 0.05). These results indicate that there is no association between these two promoter polymorphisms of LTC4S and the phenotype of AIA in a Korean population.