Background

An increase in left ventricular mass (LVM) is associated with mortality and cardiovascular morbidity in patients with end-stage renal disease.

Methods and Results

The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to 12 months of 6 times per week daily in-center hemodialysis or conventional hemodialysis; the FHN Nocturnal Trial randomized 87 patients to 12 months of 6 times per week nocturnal hemodialysis or conventional hemodialysis. The main cardiac secondary outcome was change in LVM. In each trial, we examined whether several pre-defined baseline demographic or clinical factors, as well as change in volume removal, blood pressure or solute clearance influenced the effect of frequent hemodialysis on LVM. In the Daily Trial, frequent hemodialysis resulted in a significant reduction in LVM (13.1(95% CI 5.0 to 21.3) g, p=0.002), LVM index (6.9 (2.4 to 11.3) g/m2, p=0.003) and percent change in geometric mean of LVM (7.0 (1.0 to 12.6)%, p =0.02). Similar trends were noted in the Nocturnal Trial but did not reach statistical significance. In the Daily Trial, a more pronounced effect of frequent hemodialysis on LVM was evident among patients with left ventricular hypertrophy at baseline. Changes in LVM were associated with changes in blood pressure (conventional hemodialysis: R=0.28, P=0.01, daily hemodialysis: R=0.54, P<0.001) and were not significantly associated with changes in other parameters.

Conclusions

Frequent in-center hemodialysis reduces LVM. The benefit of frequent hemodialysis on LVM may be mediated by salutary effects on blood pressure.

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/Vurea, a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome.

Background

Poor sleep quality is a common, persistent, and important problem to patients with end-stage renal disease (ESRD). This report examines whether sleep quality is associated with dialysis treatment factors and other modifiable clinical factors in a large group of hemodialysis (HD) patients.

Methods

Cross-sectional analyses were conducted on baseline data collected from participants in the Frequent Hemodialysis Network trials. Sleep quality was measured using the Medical Outcomes Study Sleep Problems Index II (SPI II), a 9-item measure of sleep quality with higher scores reflecting poorer sleep quality.

Results

The participants had an age of 51.2 ± 13.6 years, 61% were male, 38% were black, and 42% had diabetes. Higher pre-dialysis serum phosphorus (per 0.5 mg/ml) (OR 0.91; 95% CI 0.85, 0.96) and depression (OR 0.16; 95% CI 0.10, 0.25) were independently associated with decrements in sleep quality. There was also a difference in time to recovery from dialysis for the fourth versus the first SPI II quartile (5.1 h; p < 0.0001).

Conclusion

These findings underscore the link between sleep and daytime function and suggest that improving sleep may provide an opportunity to improve outcomes in ESRD. Whether sleep problems may be improved by reduction of serum phosphorus or treatment of depression in the HD population merits further investigation.

Background

Many nephrology observational studies use renal registries, which have well known limitations. The Canadian Kidney Disease Cohort Study (CKDCS) is a large prospective observational study of patients commencing hemodialysis in five Canadian centers. This study focuses on delineating potentially reversible determinants of adverse outcomes that occur in patients receiving dialysis for end-stage renal disease (ESRD).

Methods/Design

The CKDCS collects information on risk factors and outcomes, and stores specimens (blood, dialysate, hair and fingernails) at baseline and in long-term follow-up. Such specimens will permit measurements of biochemical markers, proteomic and genetic parameters (proteins and DNA) not measured in routine care. To avoid selection bias, all consenting incident hemodialysis patients at participating centers are enrolled, the large sample size (target of 1500 patients), large number of exposures, and high event rates will permit the exploration of multiple potential research questions.

Preliminary Results

Data on the baseline characteristics from the first 1074 subjects showed that the average age of patients was 62 (range; 50-73) years. The leading cause of ESRD was diabetic nephropathy (41.9%), and the majority of the patients were white (80.0%). Only 18.7% of the subjects received dialysis in a satellite unit, and over 80% lived within a 50 km radius of the nearest nephrologist's practice.

Discussion

The prospective design, detailed clinical information, and stored biological specimens provide a wealth of information with potential to greatly enhance our understanding of risk factors for adverse outcomes in dialysis patients. The scientific value of the stored patient tissue will grow as new genetic and biochemical markers are discovered in the future.

Background

Fluid accumulation in the neck during recumbency might narrow the upper airway (UA) and thereby contribute to its collapse in patients with obstructive sleep apnoea (OSA). It is hypothesised that acute fluid shifts from the legs to the upper body in healthy subjects would increase neck circumference and reduce the cross‐sectional area of the UA (UA‐XSA).

Methods

In 27 healthy non‐obese subjects of mean (SE) age 39 (3) years and body mass index 23.2 (0.6) kg/m2 studied while supine, leg fluid volume was measured using bioelectrical impedance, neck circumference using a mercury strain gauge and mean UA‐XSA between the velum and the glottis using acoustic pharyngometry at end expiration. Measurements were made at baseline after which subjects were randomly assigned to a 5 min time control period or to a 5 min application of lower body positive pressure (LBPP) at 40 mm Hg by anti‐shock trousers, separated by a 15 min washout period. Subjects then crossed over to the opposite arm of the study.

Results

Compared with control, application of LBPP significantly reduced leg fluid volume (p<0.001) and increased neck circumference (p<0.001), both at 1 min and 5 min, and reduced UA‐XSA after both 1 min (−0.15 cm2; 95% CI −0.23 to −0.09, p<0.001) and 5 min (−0.20 cm2; 95% CI −0.33 to −0.09, p<0.001).

Conclusion

In healthy subjects, displacement of fluid from the legs by LBPP causes distension of the neck and narrowing of the UA lumen. Fluid displacement from the lower to the upper body while recumbent may contribute to pharyngeal narrowing and obstruction to airflow in patients with OSA. This may have particular pathological significance in oedematous states such as heart and renal failure.

In the title dinuclear complex, [CuGd(C20H22N2O4)(NO3)3], the CuII ion is located in the inner N2O2 cavity of the Schiff base ligand and adopts a distorted square-planar geometry. The GdIII ion is ten-coordinate being bound to ten O atoms, four from the Schiff base ligand and six from three bidentate nitrate anions. The CuII and GdIII ions are linked by two phenolate O atoms of the Schiff base ligand, with a separation of 3.5185 (9) Å.

Prenatal cocaine exposure produces sustained neurobehavioral and brain synaptic changes closely resembling those of animals with defective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamatergic receptors (AMPARs). We hypothesized that prenatal cocaine exposure attenuates AMPAR signaling by interfering with AMPAR synaptic targeting. AMPAR function is governed by receptor cycling on and off the synaptic membrane through its interaction with GRIP, a PDZ domain protein that is regulated by reversible phosphorylation. Our results show that prenatal cocaine exposure markedly reduces AMPAR synaptic targeting and attenuates AMPAR-mediated synaptic long-term depression (LTD) in the frontal cortex of 21-day-old rats. This cocaine effect is the result of reduced GRIP – AMPAR interaction caused by persistent phosphorylation of GRIP by protein kinase C (PKC) and Src tyrosine kinase. These data support the restoration of AMPAR activation via suppressing excessive PKC-mediated GRIP phosphorylation as a novel therapeutic approach to treat the neurobehavioral consequences of prenatal cocaine.

Natural killer (NK) cells and CD8 T cells require adhesion molecules for migration, activation, expansion, differentiation, and effector functions. DNAX accessory molecule 1 (DNAM-1), an adhesion molecule belonging to the immunoglobulin superfamily, promotes many of these functions in vitro. However, because NK cells and CD8 T cells express multiple adhesion molecules, it is unclear whether DNAM-1 has a unique function or is effectively redundant in vivo. To address this question, we generated mice lacking DNAM-1 and evaluated DNAM-1–deficient CD8 T cell and NK cell function in vitro and in vivo. Our results demonstrate that CD8 T cells require DNAM-1 for co-stimulation when recognizing antigen presented by nonprofessional antigen-presenting cells; in contrast, DNAM-1 is dispensable when dendritic cells present the antigen. Similarly, NK cells require DNAM-1 for the elimination of tumor cells that are comparatively resistant to NK cell–mediated cytotoxicity caused by the paucity of other NK cell–activating ligands. We conclude that DNAM-1 serves to extend the range of target cells that can activate CD8 T cell and NK cells and, hence, may be essential for immunosurveillance against tumors and/or viruses that evade recognition by other activating or accessory molecules.