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.     

Oral health of hemodialysis patients: a cross-sectional study at two German dialysis centers

The aim of the study was to investigate the oral hygiene behavior and state of oral health of hemodialysis (HD) patients in Germany. HD patients attending two dialysis centers were asked to participate in the study. Anamneses and oral hygiene behavior were recorded in a questionnaire. Dental examination included the dental status (DMF-T) and the degree of gingival inflammation (PDI: Periodontol Disease Index). Of 129 patients contacted, 54 (42%), aged 63.9 ± 13.0 years (23 women and 31 men), took part in the study. At an average, dialysis was required for 4.1 years. The cause of terminal renal failure was glomerulonephritis in 30% of patients and diabetic nephropathy in 22% of patients. Since dialysis therapy, 63% of the patients (n = 34) only visited a dentist when they had complaints. In 46 cases (85%), the dentist had been informed about the patient's requirement for dialysis, and in most cases (70%), the dental treatment took place on the day after dialysis. The mean DMF-T of the HD patients was 22.1 ± 6.5. The proportion of carious teeth was low (D-T: 0.7 ± 1.2), of missing teeth (M-T) high (16.2 ± 9.3). The median degree of gingival inflammation (PDI) was 1. Availing themselves of dental treatment after patients needed to have dialysis was mostly "complaint oriented." In addition to a high proportion of missing teeth, a good level of restoration of caries was found. The gingiva showed only a low level of inflammatory changes.     

Effects of l‐carnitine supplement on serum inflammatory cytokines,C‐reactive protein,lipoprotein (a), and oxidative stress in hemodialysis patients with Lp (a) hyperlipoproteinemia

Inflammation, oxidative stress, and high concentration of serum lipoprotein (a) [Lp (a)] are common complications in hemodialysis patients. The present study was designed to investigate the effects of l ‐carnitine supplement on serum inflammatory cytokines, C‐reactive protein (CRP), Lp (a), and oxidative stress in hemodialysis patients with Lp (a) hyperlipoproteinemia [hyper Lp (a)]. This was an unblinded, randomized clinical trial. Thirty‐six hyper Lp (a) hemodialysis patients (23 men and 13 women) were randomly assigned to either a carnitine or control group. Patients in the carnitine group received 1000 mg/d oral l ‐carnitine for 12 weeks, whereas patients in the control group did not receive any l ‐carnitine supplement. At baseline and the end of week 12, 5 mL of blood were collected after a 12‐ to 14‐hours fast and serum free carnitine, CRP, interleukin‐1β, interleukin‐6 (IL‐6), tumor necrosis factor‐α, Lp (a), and oxidized low‐density lipoprotein were measured. Serum free carnitine concentration increased significantly by 86% in the carnitine group at the end of week 12 compared with baseline (P<0.001), while serum CRP and IL‐6 showed a significant decrease of 29% (P<0.05) and 61% (P<0.001), respectively. No significant changes were observed in serum free carnitine, CRP, and IL‐6 in the control group. There were no significant differences between the two groups in mean changes of serum interleukin‐1β, tumor necrosis factor‐α, Lp (a), and oxidized low‐density lipoprotein concentrations. l ‐carnitine supplement reduces inflammation in hemodialysis patients, but has no effect on hyper Lp (a) and oxidative stress.     

Lower C‐reactive protein and better hemodialysis survival are associated with regular exercise activity: Longitudinal outcomes from the ACTIVE‐ADIPOSE special study

Introduction Cross‐sectional and longitudinal studies in the general population have shown that a physically active lifestyle may have anti‐inflammatory properties, but evidence from studies conducted with maintenance hemodialysis (HD) patients is limited. Methods A multicenter prospective cohort of 755 HD participants aged 20–92 was evaluated in a USRDS special study 2009–2013. Kilocalories/week (kcal/week) of leisure time physical activity (LTPA) was estimated from the Minnesota Leisure Time Activity questionnaire. Predialysis serum samples were obtained concurrent with LTPA report date. Generalized estimating equations (GEE) examined association of participants’ LTPA and log‐normalized CRP across 24 months. Cox proportional hazards models investigated LTPA and survival over a median follow‐up of 718 days. Findings Baseline median CRP concentration was lower for participants with 500+ kcal/week LTPA vs. those with <500 kcal/week LTPA (3.4 mg/L vs. 4.6 mg/L; P = 0.03). Participants who reported lower LTPA (<500 kcal/week) at both baseline and 12 months had a borderline significant increase in CRP concentration (within‐group change 4.8 [1.9–10.4] to 5.8 [1.6–15.7]; P = 0.08). Lower LTPA was associated with higher log CRP over 24 months in adjusted GEE analyses (β coefficient = 0.16 [95% CI 0.02–0.31]; P = 0.03). 67/364 (18%) and 43/391 (11%) deaths occurred, respectively, among participants reporting <500 vs. 500+ kcal/week LTPA [adjusted mortality hazard ratio 1.63 (CI, 1.07, 2.47)]. Discussion The data suggest that increased estimated levels of LTPA, a physical activity/exercise opportunity widely applicable to HD patients, may be associated with lower CRP concentration as well as better survival outcome.     

Long‐term effects of daily hemodialysis on vascular access outcomes: A prospective controlled study

Daily hemodialysis has been associated with surrogate markers of improved survival among hemodialysis patients. A potential disadvantage of daily hemodialysis is that frequent vascular access cannulations may affect long‐term vascular access patency. The study design was a 4‐year, nonrandomized, contemporary control, prospective study of 77 subjects in either 3‐h daily hemodialysis (six 3‐h dialysis treatments weekly; n = 26) or conventional dialysis (three 4‐h dialysis treatments weekly; n = 51). Outcomes of interest were vascular access procedures (fistulagram, thrombectomy and access revision). Total access procedures (fistulagram, thrombectomy and access revision) were 543.2 (95% confidence interval [CI]: 432.9, 673.0) per 1000 person‐years in the conventional dialysis group vs. 400.8 (95% CI: 270.2, 572.4) per 1000 person‐years in the daily hemodialysis dialysis group (incidence rate ratio = 0.74 with 95% CI: from 0.40 to 1.36, P = 0.33), after adjusting for age, gender, diabetes status, serum phosphorus, hemoglobin level and erythropoietin dose, there was no significant differences in incidence rate of total access procedures (P‐value > 0.05). There was no difference in time to first access revision between the daily dialysis and the conventional dialysis groups after adjustment for covariates (hazard ratio = 0.99 95% CI: 0.42, 2.36, P = 0.96). Daily hemodialysis is not associated with increased vascular access complications, or increased vascular access failure rates.     

The long‐term effects of arteriovenous fistula creation on the development of pulmonary hypertension in hemodialysis patients

The aim of this prospective study was to evaluate long‐term effects of arteriovenous fistula (AVF) on the development of pulmonary arterial hypertension (PAH) and the relationship between blood flow rate of AVF and pulmonary artery pressure (PAP) in the patients with end‐stage renal disease (ESRD). This prospective study was performed in 20 patients with ESRD. Before an AVF was surgically created for hemodialysis, the patients were evaluated by echocardiography. Then, an AVF was surgically created in all patients. After mean 23.50 ± 2.25 months, the second evaluation was performed by echocardiography. Also, the blood flow rate of AVF was measured at the second echocardiographic evaluation. Pulmonary arterial hypertension was defined as a systolic PAP above 35 mmHg at rest. Mean age of 20 patients with ESRD was 55.05 ± 13.64 years; 11 of 20 patients were males. Pulmonary arterial hypertension was detected in 6 (30%) patients before AVF creation and in 4 (20%) patients after AVF creation. Systolic PAP value was meaningfully lower after AVF creation than before AVF creation (29.95 ± 10.26 mmHg vs. 35.35 ± 7.86 mmHg, respectively, P: 0.047). However, there was no significant difference between 2 time periods in terms of presence of PAH (P>0.05). Pulmonary artery pressure did not correlate with blood flow rate of AVF and duration after AVF creation (P>0.05). In hemodialysis patients, a surgically created AVF has no significant effect on the development of PAH within a long‐term period. Similarly, blood flow rate of AVF also did not affect remarkably systolic PAP within the long‐term period.     

Cephalic arch stenosis in patients with fistula access for hemodialysis: relationship to diabetes and thrombosis

Numerous studies have identified the fistula as the best access for hemodialysis with fewest complications. The radiocephalic fistula (RCF) is the first access of choice, but often results in poor maturation. Therefore, an increased number of brachiocephalic fistulas (BCF) have been placed. Cephalic arch stenosis (CAS) can occur in patients with fistula access. The current study was done to determine the incidence and associated comorbidities in patients with BCF or RCF who have CAS. A retrospective review of 450 hemodialysis patients in 3 outpatient hemodialysis units between July 1, 2000 and July 1, 2005 (60 months) was preformed. We reviewed demographics, medications, and indications for venograms. Interventional Radiologists reviewed the venograms for evidence of CAS. Radiology reports were screened to determine incidence of thrombosis, treatment with either angioplasty or stent placement and if a complication such as venous rupture occurred. One hundred and twenty-seven patients had fistula access with at least 1 venogram. Of these, 30 were RCF and 97 were BCF. Cephalic arch stenosis occurred in 77% of patients with BCF and in 20% of patients with RCF. Those with diabetes had a lower rate of occurrence than those without (p<0.01). Cephalic arch stenosis led to a high rate of thrombosis (p<0.01). The probability of having multiple radiology procedures was higher with CAS than without (p<0.01). Cephalic arch stenosis is an important problem in hemodialysis patients who have fistula access, and contributes to thrombosis. Diabetes was found to have a negative association with CAS for undefined reasons. Attempts to understand this relationship are important.     

Construction and validation of a scale of assessment of self‐care behaviors with arteriovenous fistula in hemodialysis

Several guidelines recommend the importance of educating the patient about the care of vascular access. Nurses have a key role in promoting the development of self‐care behaviors by providing the necessary knowledge to patients, so that they develop the necessary skills to take care of the arteriovenous fistula (AVF). This article describes the process of building a scale of assessment of self‐care behaviors with arteriovenous fistula in hemodialysis (ASBHD‐AVF). This is a cross‐sectional study in which the development, construction, and validation process followed the directions of the authors Streiner and Norman. This is a convenience sample, sequential, and nonprobabilistic constituted by 218 patients. The study was conducted in two stages during 2012–2014. The first phase corresponds to the scale construction process, 64 patients participated, while the second corresponds to the evaluation of metric properties and 154 patients participated. The principal component analysis revealed a two‐factor structure, with factorial weights between 0.805 and 0.511 and between 0.700 and 0.369, respectively, explaining 39.12% of the total variance of the responses. The Cronbach's alpha of the subscale management of signs and symptoms is 0.797 and from the subscale prevention of complications is 0.722. The ASBHD‐AVF revealed properties that allow its use to assess the self‐care behaviors in the maintenance and conservation of the AVF.     

Heparin‐induced thrombocytopenia in a hemodialysis patient treated with fondaparinux: Nephrologists between two fires

Heparin‐induced thrombocytopenia (HIT) is caused by heparin exposure and presents with reduced platelet count. Patients undergoing hemodialysis (HD) treatment have increased risk of developing HIT due to prolonged exposure to unfractionated heparin or low‐molecular weight heparin. We report a 79‐year‐old male patient with end‐stage renal disease who developed type‐II HIT during maintenance HD. Platelet count of the patient decreased gradually and antiplatelet factor IV antibody was found to be positive. The patient was treated with fondaparinux and continued heparin‐free HD. Unfortunately, despite favorable initial response without any thrombotic episodes, the patient died due to severe sepsis complicated by gastrointestinal hemorrhage.     

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.     

Long‐term effects of angiotensin II blockade with irbesartan on inflammatory markers in hemodialysis patients: A randomized double blind placebo controlled trial (SAFIR study)

Introduction: Low‐grade chronic inflammation is common in hemodialysis (HD) patients. Previous studies suggest an anti‐inflammatory effect of angiotensin II receptor blocker (ARB) treatment. The aim of this study was to compare the effect of ARB vs. placebo on plasma concentrations of inflammatory markers in HD patients. Methods: Adult HD patients were randomized for double‐blind treatment with the ARB irbesartan 150–300 mg/day or placebo. At baseline, 1 week, 3, 6, 9, and 12 months plasma high sensitivity C‐reactive protein (hsCRP), interleukin (IL)?1β, IL‐6, IL‐8, IL‐18, and transforming growth factor‐β (TGF‐β) were measured using Luminex and enzyme‐linked immunosorbent assay (ELISA) technology. Findings: Eighty‐two patients were randomized (placebo/ARB: 41/41). The groups did not differ in initial levels of any of the inflammatory markers (placebo/ARB median(range)): hsCRP 3.3(0.2–23.4)/2.7(0.2–29.6) μg/mL; IL‐1β 1.1(0.0–45.9)/1.1(0.0‐7.2) pg/mL; IL‐6 10(1–90)/12(1–84) pg/mL; IL‐8 31(9–134)/34(5–192) pg/mL; IL‐18 364(188–1343)/377(213–832) pg/mL; TGF‐β 3.2(0.8–13.9)/3.6(1.3–3.8) ng/mL. Overall, there was no significant difference in hsCRP, IL‐6, IL‐8, and TGF‐β between placebo and ARB‐treated patients during the study period, and hsCRP, IL‐6, IL‐8, and TGF‐β were relatively stable during the study period (P ≥ 0.18 in all tests for parallel curves, equal levels, and constant levels). The IL‐1β level was slightly different in the two groups over time, but not significantly (P = 0.09 in test for parallel curves) and it was also relatively stable during the study period (P ≥ 0.49 in tests for equal levels and constant level). IL‐18 was the only inflammatory marker which was not constant during the study period (P = 0.001 in test for constant level), but there was no significant difference between placebo and ARB‐treated (P ≥ 0.51 in tests for parallel curves and equal levels). Discussion: Inflammatory biomarkers were neither acutely, nor in the long‐term significantly affected by the ARB irbesartan. Our findings suggest that ARB treatment in HD patients does not offer protective anti‐inflammatory effects.     

The effect of extended‐hours hemodialysis on outcomes: A systematic review and meta‐analysis

Extended‐hours hemodialysis is associated with improvements in quality of life (QoL) and mortality, but it may accelerate the loss of residual kidney function (RKF) and increase vascular access complications. Multiple established databases were systematically searched; randomized and non‐randomized studies were pooled separately. QoL outcomes were assessed using standardized mean difference (SMD), vascular access adverse events and mortality were assessed with relative risk ratios (RR). Four hundred seventy‐six patients from six trials were eligible. Data from randomized controlled trials (RCTs) could only be synthesized for vascular access adverse events and mortality, which demonstrated no significant change in vascular access adverse events (RR 1.25, 95% CI 0.88 to 1.77) or mortality (RR 2.29, 95% CI 0.60 to 8.71). Pooled data from non‐randomized trials demonstrated no significant difference in QoL (SF‐36 Physical Component Summary SMD 0.61, 95% CI ?0.10 to 1.31, SF‐36 Mental Component Summary SMD ?0.04, 95% CI ?0.61 to 0.54). RKF was assessed in one report which demonstrated a potential reduction over 12 months with extended‐hours hemodialysis. The majority of trials had high risk of bias. Extended‐hours hemodialysis was not associated with improved QoL or mortality, or increased vascular access events. Adequately powered RCTs are needed to fully assess extended‐hours hemodialysis.     

Erythropoietin‐stimulating agents in the management of anemia of end‐stage renal disease patients on regular hemodialysis: A prospective randomized comparative study from Qatar

Despite extensive use, to the best of our knowledge, no trial has simultaneously compared the three currently used erythropoietin‐stimulating agents (ESAs) in a prospective manner in the treatment of anemia of end‐stage renal disease patients. All hemodialysis patients in Qatar who were treated with short‐acting epoetin alfa or beta have been screened. Eligible patients had been prospectively randomized, either to continue on the previous regimen of epoetin or to receive darbepoetin alfa or continuous erythropoietin receptor activator (CERA) for a total period of 40 weeks. All groups were assessed at the end of the study for safety and efficacy parameters. A total of 327 eligible patients were randomized. Mean hemoglobin concentration remained constant within the recommended target range (11–12 g/dL) throughout the study in the three studied groups. The percentage of patients who reached the target range was constantly above 50% in the second half of the study among CERA group patients who also had significantly lower mean number of dose adjustments as compared with the other two groups (P = 0.001). Similarly, the number of discontinuations of ESA among epoetin, darbepoetin, and CERA groups was 17, 19, and 9, respectively (P = 0.042). The frequencies of adverse events were similar in all groups. This study has specifically compared the effect of ESA type on the variability of serum hemoglobin levels in hemodialysis patients. Furthermore, it confirmed the efficacy and safety of once monthly CERA for maintaining tight hemoglobin control within recommended target ranges.