A single center,open‐label,randomized, parallel group study assessing the relationship between asymptomatic bacteriuria and inflammation in maintenance hemodialysis patients

Introduction: The significance of asymptomatic bacteriuria in maintenance hemodialysis (MHD) patients remains controversial. We hypothesized that the presence of asymptomatic bacteriuria as a sole clinical manifestation of urinary tract infection (UTI) in asymptomatic MHD patient may contribute to the chronic inflammatory response. Our aim was to explore the relationship between asymptomatic bacteriuria and elevated levels of inflammatory markers in MHD patients. Methods: A randomized open‐label single center study of 114 MHD patients was conducted. Forty‐six patients presented negative urine culture and 41 subjects were excluded due to different reasons. The remaining 27 patients (mean age of 71.5 ± 12.2 years, 63% men), fulfilling the criteria for having asymptomatic bacteriuria, were randomly assigned to either the treatment group (13 patients) or the observational group (14 subjects). The treatment group received 7 days of antibiotic treatment given according to bacteriogram sensitivity. After 3 months of follow‐up all measurements of the study were repeated. The primary end point was change in inflammatory biomarkers from baseline by the end of the study. Findings: There were no statistically significant differences in white blood cell changes (P = 0.27), ferritin (P = 0.09), C‐reactive protein (P = 0.90), and interleukin‐6 (P = 0.14) levels between the groups from baseline to the end of study or at the end of the study. Analyzing cross‐sectional data, asymptomatic bacteriuria was found to not be a predictor of higher levels of inflammatory parameters at baseline. Discussion: Asymptomatic bacteriuria is not a modifiable risk factor for chronic inflammation in the MHD population.     

Predialysis volume overload and patient‐reported sleep duration and quality in patients receiving hemodialysis

Introduction: Previous studies of patients with end‐stage renal disease have examined the role of fluid shifts on apnea‐hypopnea episodes, but the association between volume overload and patient‐reported sleep quality or duration has not been well‐established. Methods: We studied the association between predialysis bioimpedance spectroscopy‐derived volume estimates and self‐reported sleep quality and duration in 638 patients in the United States Renal Data System ACTIVE/ADIPOSE study receiving hemodialysis from 2009 to 2011. We used questionnaires to assess self‐reported sleep duration and quality. We used relative hydration status (fluid overload/extracellular water; FO/ECW) as the primary predictor and examined associations with hours of sleep duration using linear regression. We used multivariable ordinal logistic regression to determine the association between categories of relative hydration status (normal hydration [FO/ECW < 6.8%], mild overhydration [FO/ECW 6.8%–15%], and hyperhydration [FO/ECW > 15%]) and four levels of difficulty with falling asleep, waking, and returning to sleep. Findings: Higher relative hydration status was associated with fewer hours of sleep (?0.31 hours per 10%, 95% confidence interval (CI) ?0.49 to ?0.13). Compared to the normal hydration group, there was a statistically significant association between higher relative hydration status category and more frequent nighttime waking (OR: mild overhydration 1.92 [95% CI 1.23–2.99], hyperhydration 1.87 [95% CI 1.16–2.99]), a trend toward more difficulty returning to sleep (OR: mild overhydration 1.46 [95% CI 0.94–2.27], hyperhydration 1.52 [95% CI 0.95–2.43]), and no association between relative hydration category and difficulty falling asleep. Discussion: Hydration status was associated with self‐reported sleep duration in patients on dialysis. Future studies should prospectively examine the effects of optimizing fluid status on sleep duration and quality.     

Correlation between physical functioning and sleep disturbances in hemodialysis patients

The study set out to investigate the relationship between physical functioning, inflammatory status, and sleep disturbance in a chronic hemodialysis (HD) population. Forty-six maintenance HD patients from the McGill University Health Centre were enrolled in this study between October 2005 and 2006. The well-validated Human Activity Profile (HAP) questionnaire and the RAND 36-item survey were used to assess physical functioning. Subjects were given the Pittsburgh Sleep Quality Index (PSQI) survey to evaluate the degree of sleep disturbance. Inflammatory status was assessed with the average value of serial C-reactive protein (CRP) levels for each patient, over a period of 12 months before their enrollment in the study. A multivariate logistic regression model was created for these analyses to control for potential confounders, including dialysis adequacy, inflammation, and hemoglobin. Seventy-six percent of the study population had poor sleep as per the Pittsburgh Sleep Quality Index (PSQI score > or = 5). In addition, 65% of subjects had high CRP values (>5 mg/L). On univariate analysis, both a CRP >5 mg/L and a lower adjusted activity score (AAS) on the HAP were significantly associated with poor sleep (PSQI score > or = 5). Multivariate logistic analysis demonstrated that the AAS remained significantly associated with poor sleep, with a 6% decrease in the odds of poor sleep for each score increase in the AAS of the HAP. Poor physical functioning in chronic HD patients, as measured by the HAP, is associated with sleep disturbance, after controlling for inflammation and dialysis adequacy.     

Clinical and psychosocial factors predicting health‐related quality of life in hemodialysis patients

Many patients with end‐stage renal disease have significant impairment in health‐related quality of life (HRQoL). Most previous studies have focused on clinical factors; however, quality of life can also be affected by psychosocial factors. The aim of this study was to identify the possible predictors of HRQoL among clinical and psychosocial factors in hemodialysis (HD) patients. The study included 101 patients who were undergoing HD. Psychosocial factors were evaluated using the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Montreal Cognitive Assessment, and Pittsburgh Sleep Quality Index. We also assessed laboratory and clinical factors, including albumin, Kt/V as a marker of dialysis adequacy, normalized protein catabolic rate, and duration of HD. The Euro Quality of Life Questionnaire 5‐Dimensional Classification (EQ‐5D) was used to evaluate HRQoL. The mean EQ‐5D index score was 0.704 ± 0.199. The following variables showed a significant association with the EQ‐5D index: age (P < 0.001), depression (P < 0.001), anxiety (P < 0.001), support from friends (P < 0.001), cognitive function (P < 0.001), duration of HD (P = 0.034), triglyceride (P = 0.031), total iron‐binding capacity (P = 0.036), and phosphorus (P = 0.037). Multiple regression analysis showed that age (95% confidence interval [CI] ?0.008 to ?0.002), anxiety (95% CI ?0.025 to ?0.009), and support from friends (95% CI 0.004 to 0.018) were independent predictors of impaired HRQoL. This study explored determinants of impaired HRQoL in HD patients. We found that impaired HRQoL was independently associated with age, anxiety, and support from friends. We should consider psychosocial as well as clinical factors when evaluating ways to improve HRQoL in HD patients.     

Self‐perceived quality of sleep and mortality in Norwegian dialysis patients

Sleep complaints are prevalent and associated with poor health‐related quality of life (HRQoL), depression and possibly mortality in dialysis patients. This study aimed to explore possible associations between sleep quality, daytime sleepiness and mortality in dialysis patients. In this study, 301 dialysis patients were followed up to 4.3 years. HRQoL was evaluated at baseline with the Kidney Disease and Quality of Life—Short Form (KDQoL‐SF), depression with Beck Depression Inventory (BDI), sleep quality with Pittsburgh Sleep Quality Index and daytime sleepiness with Epworth Sleepiness Scale. The single item “on a scale from 0–10, how would you evaluate your sleep?” in the sleep subscale in KDQoL‐SF was used to identify poor (0–5) and good sleepers (6–10). A total of 160 patients (53.3%) were characterized as poor sleepers. They were younger (r = 0.241, P < 0.001), had more depression (BDI: 8.72 ± 6.79 vs. 13.60 ± 8.04, P < 0.001), a higher consumption of hypnotics and antidepressants and reduced HRQoL (Mental Component Summary score: 45.4 ± 11.0 vs. 50.0 ± 10.4, P < 0.001. Physical Component Summary score: 35.0 ± 9.9 vs. 38.5 ± 10.5, P = 0.004). In multivariate analyses, poor sleepers had nearly a twofold increase in mortality risk (hazard ratio [HR] 1.92, confidence interval [CI] 1.10‐3.35, P = 0.022). Daytime sleepiness was not related to mortality (HR 1.01, CI 0.95‐1.08, P = 0.751). Sleep complaints predicted increased mortality risk in dialysis patients and should therefore be routinely assessed. Further studies are needed to find suitable treatment options for poor sleep in dialysis patients as it may affect both HRQoL and survival.     

Cultural comparison of symptoms in patients on maintenance hemodialysis

Although symptoms are common and frequently severe in patients on maintenance hemodialysis, little is known about the relationship between cultural background and symptom burden. The aim of this study was to explore differences in the prevalence and severity of symptoms between American and Italian hemodialysis patients. We administered the 30‐item Dialysis Symptom Index to American and Italian patients receiving maintenance hemodialysis during routine dialysis sessions. The prevalence and severity of individual symptoms were compared between patient populations, adjusting for multiple comparisons. Multivariable logistic regression and ordinal logistic regression were used to assess the independent associations of cultural background with the prevalence and severity of symptoms, respectively. We enrolled 75 American and 61 Italian patients. American patients were more likely to be black (36% vs. 0%, P<0.001) and diabetic (53% vs. 13%, P<0.001). Italian patients were more likely to report decreased interest in sex, decreased sexual arousal, feeling nervous, feeling irritable, and worrying (P<0.001, respectively). Adjustment for demographic and clinical variables had no impact on these cultural differences in symptom prevalence. The median severity of 11 symptoms including muscle soreness, muscle cramps, and itching was greater among Americans (P<0.001, respectively), although nearly all of these differences were rendered nonstatistically significant with adjustment for race, diabetes, and/or Kt/V. Italian patients receiving chronic hemodialysis report a greater burden of symptoms than American patients, particularly those related to sexual dysfunction and psychosocial distress. These findings suggest that cultural background may affect adaptation to chronic hemodialysis therapy.     

Associations among nocturnal sleep,daytime intradialytic sleep,and mortality risk in patients on daytime conventional hemodialysis: US Renal Data System special study data

Fragmented nocturnal sleep is commonly reported by patients undergoing daytime conventional hemodialysis (CHD) and may be associated with higher mortality risk. Subjective sleepiness during CHD is also frequently observed. We examined the association of reported sleep fragmentation and nocturnal and daytime (intradialytic) sleep durations with survival in a national cohort of 1440 CHD patients who were interviewed in 2005–2007 in a phone survey conducted by the US Renal Data System. Patient survival was followed through September 30, 2010 in the US Renal Data System. A total of 76% of patients reported that they typically dozed off or slept during their treatment, and intradialytic dozing was especially common among patients whose treatment shift started before 1000 hours. There was a trend for patients who reported dozing during CHD to report nocturnal sleep fragmentation (60.4% vs. 55.1%; P = 0.07). With adjustment for intradialytic sleep and other covariates, nocturnal sleep fragmentation was not associated with survival. Mortality risk was higher for patients who reported sleeping 9 or more hours/night compared with the referent category of nocturnal sleep equal to 6–7 hours (hazard ratio: 1.50 [95% confidence interval: 1.04–2.17]; P = 0.03). Continued investigation of the association of timing and duration of sleep with hemodialysis patient outcomes is warranted.     

Correlation between coping style and quality of life among hemodialysis patients from a low‐income area in Brazil

Quality of life (QOL) is an important outcome among end‐stage renal disease patients and can be associated with modifiable behaviors. We analyzed the correlation between coping style and QOL among hemodialysis patients. We studied 166 end‐stage renal disease patients undergoing hemodialysis. They were older than 18 years, under hemodialysis for at least 3 months, and had never received a transplant. Quality of life was assessed by SF‐36 and coping style was scored by the Jalowiec Coping Scale. Emotion‐oriented coping and problem‐oriented coping scores were compared according to sex, comorbidity, and socioeconomic status by the Mann‐Whitney test. Correlations between QOL and 2 coping styles (emotion‐oriented coping and problem‐oriented coping) were adjusted for age, time on dialysis, hemoglobin, creatinine, albumin, calcium–phosphorus product, and Kt/V by backward stepwise linear regression. There was no difference between coping scores according to sex, comorbidity, and socioeconomic status. Emotion‐oriented coping was independently and negatively associated with 4 QOL dimensions: physical functioning, role‐physical, role‐emotional, and mental health. Our results indicate that patients with high emotion‐oriented coping scores should be seen at risk for poor QOL. Patient education in coping skills may be used to change the risk of poor QOL.     

Association of serum alkaline phosphatase and bone mineral density in maintenance hemodialysis patients

Recent studies indicate that serum alkaline phosphatase (AlkPhos), a surrogate of high turnover bone disease, is associated with coronary artery calcification and death risk in maintenance hemodialysis (MHD) patients. The association between AlkPhos and bone mineral density (BMD) is not well studied. We studied the association between AlkPhos and dual‐energy X‐ray absorptiometry‐assessed BMD in a group of MHD patients in Southern California. In 154 MHD patients, aged 55.3 ± 13.6 years, including 42% women, 38% Hispanics, 42% African Americans, and 55% diabetics, the mean serum AlkPhos was 121 ± 63 U/L (median: 101, Q_25–75: 81–141); 36% had AlkPhos≥120 U/L and 50% had a total T‐score≤?1. Whereas the total BMD did not correlate with age (r=0.01, P=0.99) or body mass index (r=0.10, P=0.22), it correlated negatively with AlkPhos (r=?0.25, P=0.002), including after multivariate adjustment (r=?0.24, P=0.003). The proportion of patients with a high coronary artery calcification score>400 was incrementally higher across worsening BMD tertiles (P trend=0.04). The BMD was significantly worse in MHD patients with serum AlkPhos≥120 U/L compared with <120 U/L (1.01 ± 0.016 vs. 1.08 ± 0.013 g/cm², respectively, P<0.001). The multivariate adjusted odds ratio of AlkPhos≥120 U/L for having a total T‐score相似文献   

Anti‐inflammatory effects of linagliptin in hemodialysis patients with diabetes

Inflammation and glycemic control are important prognosis‐related factors for hemodialysis (HD) patients; moreover, inflammation affects insulin secretion. Here, we evaluated the anti‐inflammatory effects of monotherapy with linagliptin—a dipeptidase‐4 inhibitor—in HD patients with type 2 diabetes. We examined 21 diabetic HD patients who were not receiving oral diabetes drugs or insulin therapy and with poor glycemic control (glycated albumin [GA] level, >20%). Linagliptin (5 mg) was administered to the patients daily. The levels of prostaglandin E2 (PGE2), interleukin‐6 (IL‐6), high‐sensitivity C‐reactive protein, GA, blood glucose, and active glucagon‐like peptide‐1 were determined before and 6 months after treatment. Body weight and serum levels of albumin, hemoglobin, total cholesterol, and low‐density lipoprotein cholesterol were also recorded before and after treatment. The levels of PGE2 and GA were significantly decreased 1 month after starting linagliptin therapy, whereas the IL‐6 levels were significantly decreased 6 months after starting linagliptin therapy. After 6 months of treatment, the PGE2 levels decreased from 188 ± 50 ng/mL to 26 ± 5 ng/mL; IL‐6 levels, from 1.5 ± 0.4 pg/mL to 0.6 ± 0.1 pg/mL; and GA levels, from 21.3% ± 0.6% to 18.0% ± 0.6%. Glucagon‐like peptide‐1 levels increased 2.5‐fold during the treatment. Over the 6‐month treatment period, body weight and levels of high‐sensitivity C‐reactive protein, blood glucose, albumin, hemoglobin, and cholesterol did not change; none of the patients exhibited hypoglycemia. The anti‐inflammatory effects of linagliptin monotherapy indicate that it may serve as a useful glucose control strategy for HD patients with diabetes.     

Association between afebrile status and in‐hospital mortality among adult chronic hemodialysis patients with bacteremia

Aim: We aimed to compare the in‐hospital mortality between febrile and afebrile chronic hemodialysis (HD) patients with bacteremia and analyze the blood culture positive rate according to the C‐reactive protein (CRP) level. Methods: We collected data from 2006 to 2014. One hundred ninety bacteremic events were assigned to the “febrile group” (n = 162) and “afebrile group” (n = 28) based on the presence of fever. Fever was defined as a tympanic temperature >37.5°C or axillary temperature >37.0°C. Results: In‐hospital mortality (41.4% vs. 6.1%) was higher; and the interval between admission and blood culture was longer (3 vs. 1 h) in the afebrile group than in the febrile group. The mean reason for blood culture in the afebrile group was a high CRP level. Conclusions: An afebrile status in HD patients with bacteremia is associated with higher in‐hospital mortality. Blood culture and empirical antibiotic administration, irrespective of the fever status, should be considered in HD patients with a CRP ≥ 5 mg/dL.     

Coenzyme Q10 supplementation and diastolic heart functions in hemodialysis patients: A randomized double‐blind placebo‐controlled trial

Coenzyme Q10 (CoQ10) supplementation has been shown to improve diastolic heart function in various patient cohorts. Systolic and diastolic dysfunctions are common in patients with end‐stage renal disease. Favorable effects of CoQ10 on cardiac functions are yet to be seen in hemodialysis patients. We aimed to evaluate effect of CoQ10 supplementation on diastolic function in a cohort of maintenance hemodialysis patients. This was a prospective, double‐blind, placebo‐controlled, crossover study in which all patients received placebo and oral CoQ10 200 mg/d during the 8 weeks in each phase, with a 4‐week washout period. Participants underwent conventional and tissue Doppler echocardiography before and after each study phase. Parameters characterizing left ventricle diastolic function and other standard echocardiographic measurements were recorded. Twenty‐eight patients were randomized, but 22 patients completed study protocol. Intraventricular septum (IVS) thickness and left ventricle mass were significantly decreased in CoQ10 group (P = 0.03 and P = 0.01, respectively). Myocardial peak systolic and early diastolic velocities derived from IVS were significantly increased (P = 0.048 and P = 0.04, respectively). Isovolumetric relaxation time and E/Em ratio calculated for IVS also significantly reduced in CoQ10 group (p = 0.02 and p = 0.04, respectively). There was no significant difference in any of the studied echocardiographic parameters in placebo group. The results of this study showed that CoQ10 supplementation did not significantly improved diastolic heart functions compared with placebo in maintenance hemodialysis patients.     

FGF‐23 and cognitive performance in hemodialysis patients

Although cognitive impairment is common in hemodialysis patients, the etiology of and risk factors for its development remain unclear. Fibroblast growth factor 23 (FGF‐23) levels are elevated in hemodialysis patients and are associated with increased mortality and left ventricular hypertrophy. Despite FGF‐23 being found within the brain, there are no prior studies assessing whether FGF‐23 levels are associated with cognitive performance. We measured FGF‐23 in 263 prevalent hemodialysis patients in whom comprehensive neurocognitive testing was also performed. The cross‐sectional association between patient characteristics and FGF‐23 levels was assessed. Principal factor analysis was used to derive two factors from cognitive test scores, representing memory and executive function, which carried a mean of 0 and a standard deviation of 1. Multivariable linear regression adjusting for age, sex, education status, and other relevant covariates was used to explore the relationship between FGF‐23 and each factor. Mean age was 63 years, 46% were women and 22% were African American. The median FGF‐23 level was 3098 RU/mL. Younger age, lower prevalence of diabetes, longer dialysis vintage, and higher calcium and phosphorus were independently associated with higher FGF‐23 levels. Higher FGF‐23 was independently associated with a lower memory score (per doubling of FGF‐23, β = ?0.08 SD [95% confidence interval, CI: ?0.16, ?0.01]) and highest quartile vs. lowest quartile (β = ?0.42 SD [?0.82, ?0.02]). There was no definite association of FGF 23 with executive function when examined as a continuous variable (β = ?0.03 SD [?0.10, 0.04]); however, there was a trend in the quartile analysis (β = ?0.28 SD [?0.63, 0.07], P = 0.13, for 4th quartile vs. 1st quartile). FGF‐23 was associated with worse performance on a composite memory score, including after adjustment for measures of mineral metabolism. High FGF‐23 levels in hemodialysis patients may contribute to cognitive impairment.     

Infective spondylodiscitis in patients on high‐flux hemodialysis and on‐line hemodiafiltration

Infective spondylodiscitis (ISD) is a rare but potentially devastating condition in hemodialysis (HD) patients. Reports are limited especially in patients receiving high‐flux HD and hemodiafiltration (HDF). In a retrospective analysis, 13 patients on our maintenance high‐flux HD/HDF program were identified as having has infective spondylodiscitis over a 10‐year period (1997–2006), an incidence of approximately 1 episode every 215 patient‐years. The incidence was around 3 times higher in patients dialyzing with tunnelled central venous catheters (TCVC) than in those with arteriovenous fistulae. Affected patients were elderly (mean age 70 years) and had multiple comorbidities. Access problems, particularly TCVC infection, were common in the months preceding it's onset. Tunnelled central venous catheter removal during these episodes did not necessarily prevent it. Diagnosis was based on a history of back pain, raised C‐reactive protein, positive blood cultures, and characteristic magnetic resonance findings. Many patients were apyrexial and had normal white cell counts. In our patients on high‐flux HD/hemodiafiltration, its incidence appears comparable to that in conventional HD settings. No patients had infection with waterborne organisms. Blood cultures were positive in 77%. Gram‐positive organisms predominated, particularly Staphylococcus aureus. The major route of infection was hematogenous, with the most likely source the venous access. All received antibiotics for 6 to 12 weeks or until death. Only 2 patients underwent surgical drainage. Mortality was high (46%) and predicted by the development of complications, and by pre‐existing cardiovascular comorbidity. Prevention, using strategies to reduce the prevalence of bacteremia, including limiting the use of TCVC, should be an overriding aim.     

Effect of serum FGF‐23, MGP and fetuin‐A on calcium‐phosphate metabolism in maintenance hemodialysis patients

This study was aimed to explore the role of serum fibroblast growth factor (FGF)‐23, matrix Gla protein (MGP) and fetuin‐A in the calcium‐phosphate metabolism and their predicting value in coronary artery calcification in maintenance hemodialysis (MHD) patients. This study included 64 patients who receive hemodialysis in our hospital. The serum FGF‐23, MGP and fetuin‐A were analyzed by enzyme‐linked immunosorbent assay (ELlSA). Coronary artery calcification score (CACS) was evaluated by coronary artery computed tomography scan. The 64 patients (30 males, 34 females, 60.6 ± 11.3 years of age) received an average dialysis vintage of 6.88 ± 2.94 years. We divided the CACS into three levels, and 13 (20.31%), 16 (25%), and 35 (54.69%) exhibited a CACS of 0–100, 100–400, and >400, respectively. Dialysis vintage, serum FGF‐23, fetuin‐A, phosphorus and high‐density lipoprotein‐C levels were identified as independent variables of CACS by stepwise multiple regression analysis. The area under receiver operating characteristic curve indicated that serum FGF‐23 and fetuin‐A were useful for identifying CAC in MHD patients. The cut‐off value corresponding to the highest Youden's index was serum FGF‐23 ≥ 256 pg/mL and fetuin‐A ≤ 85 μg/mL, which was defined as the optimal predictors of CAC. Different combinations of serum FGF‐23 and fetuin‐A in parallel or in series effectively boosted the identification of CAC. The incidence of CAC is high in MHD patients. Serum FGF‐23 and fetuin‐A levels are closely correlated with CAC.     

The interleukin-10 promoter genotype predicts diastolic dysfunction in maintenance hemodialysis patients

Interleukin-10 (IL-10) predominantly acts as an anti-inflammatory factor. Polymorphisms in the IL-10 gene promoter determine quantitative cytokine production. Doppler echocardiography and tissue Doppler imaging (TDI) are superior to conventional echocardiography to evaluate diastolic dysfunction. The IL-10 gene promoter polymorphism at position (-1082) was studied for its association with conventional and Doppler echocardiographic and TDI parameters in 112 hemodialysis (HD) patients. Blood pressure, serum C-reactive protein (CRP), and albumin levels were also examined for the association study. The genetic association study showed that among the HD patients, there was no difference in the prevalence of systolic and diastolic dysfunction between genotypes on conventional echocardiography. However, using Doppler echocardiography and TDI, high producers for the IL-10 -1082 promoter (-1082/GG) have higher E velocities, E/A values, lateral, and septal E' velocities and a lower isovolumic ventricular relaxation time than low (-1082/AA) and intermediate producers (-1082/GA). Significantly higher levels of serum CRP levels and lower plasma albumin levels were found in low and intermediate producers for the IL-10 -1082 promoter than high producers. The IL-10 genotype may balance the effects of inflammatory cytokines on the myocardium and may be a determinant of LV function in HD patients.