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.     

Febuxostat improves endothelial function in hemodialysis patients with hyperuricemia: A randomized controlled study

Endothelial dysfunction is often found in both hyperuricemia and hemodialysis patients. Recent studies have shown that treating hyperuricemia with allopurinol improves endothelial dysfunction. This study is performed to assess the effect of febuxostat on endothelial dysfunction in hemodialysis patients with hyperuricemia. We randomly assigned 53 hemodialysis patients with hyperuricemia to a febuxostat (10 mg daily) group and a control group and measured flow‐mediated dilation, serum uric acid (UA) levels, systolic and diastolic blood pressure, malondialdehyde‐modified low‐density lipoprotein (MDA‐LDL), and highly sensitive C‐reactive protein (hsCRP) at baseline and at the end of a 4‐week study period. Flow‐mediated dilation increased from 5.3% ± 2.4% to 8.9% ± 3.6% in the febuxostat group but did not change significantly in the control group. Treatment with febuxostat resulted in a significant decrease in serum UA level and a significant decrease in MDA‐LDL compared with baseline, but no significant difference was observed in hsCRP level or blood pressure. No significant differences were observed in the control group. Febuxostat improved endothelial dysfunction and reduced serum UA levels and oxidative stress in hemodialysis patients with hyperuricemia.     

The effects of nocturnal compared with conventional hemodialysis on mineral metabolism: A randomized‐controlled trial

Hyperphosphatemia is common among patients receiving dialysis and is associated with increased mortality. Nocturnal hemodialysis (NHD) is a long, slow dialytic modality that may improve hyperphosphatemia and disorders of mineral metabolism. We performed a randomized‐controlled trial of NHD compared with conventional hemodialysis (CvHD); in this paper, we report detailed results of mineral metabolism outcomes. Prevalent patients were randomized to receive NHD 5 to 6 nights per week for 6to 10 hours per night or to continue CvHD thrice weekly for 6 months. Oral phosphate binders and vitamin D analogs were adjusted to maintain phosphate, calcium and parathyroid hormone (PTH) levels within recommended targets. Compared with CvHD patients, patients in the NHD group had a significant decrease in serum phosphate over the course of the study (0.49 mmol/L, 95% confidence interval 0.24–0.74; P=0.002) despite a significant reduction in the use of phosphate binders. Sixty‐one percent of patients in the NHD group compared with 20% in the CvHD group had a decline in intact PTH (P=0.003). Nocturnal hemodialysis lowers serum phosphate, calcium‐phosphate product and requirement for phosphate binders. The effects of NHD on PTH are variable. The impact of these changes on long‐term cardiovascular and bone‐related outcomes requires further investigation.     

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.     

Effect of needle orientation during arteriovenous access puncture on needed compression time after hemodialysis: A randomized controlled trial

Background

There are two techniques for puncturing an arteriovenous fistula: one where the needle is inserted bevel up and then rotated to a bevel down position, and another where the needle is inserted bevel down. The aim of this study was to compare these two methods of needle insertion on minimum compression time required for hemostasis after needle removal.

Methods

This was a prospective, randomized, cross-over, blinded, single-center, routine care study. Each patient's average post-dialysis puncture site compression time was determined during a 2-week baseline period while using bevel-up access puncture. Subsequently, minimum post-dialysis puncture-site compression time was determined during each of two sequential follow-up periods, during which fistula puncture was done with needles inserted bevel up or down, respectively. The order of treatments (bevel up or bevel down insertion) was randomized. During each follow-up period, the minimum compression time necessary to avoid bleeding on needle removal was determined by progressively shortening the compression time. Puncture-associated pain was also assessed as prepump and venous pressures and ability to achieve desired blood flow rate during the dialysis session.

Results

Forty-two patients were recruited. The baseline compression time after needle removal averaged 9.99 ± 2.7 min During the intervention periods, the minimum compression time was on average 10.8 min (9.23–12.4) when the access needles had been inserted bevel down versus 11.1 min (9.61–12.5) when the access needles had been inserted bevel up (p = 0.72). There was no difference in puncture-associated pain between the two insertion techniques, and no difference in prepump or venous pressures or ability to achieve the desired blood flow rate during the dialysis session.

Conclusion

Bevel-up and bevel-down needle orientation during arteriovenous fistula puncture are equivalent techniques in terms of achieving hemostasis on needle removal, and puncture-associated pain.     

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.     

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 effects of single hemodialysis session on arterial stiffness in hemodialysis patients

Increased arterial stiffness in hemodialysis patients is a strong predictor of cardiovascular morbidity and mortality. Pulse wave velocity (PWV) and augmentation index (AIx), which are markers of arterial stiffness, were used to determine the severity of vascular damage noninvasively. This study aimed to investigate the effects of solute volume removal and hemodynamic changes on PWV and AIx of a single hemodialysis session. Thirty hemodialysis patients were enrolled in the study. Before initiation of hemodialysis, every 15 minutes during hemodialysis, and 30 minutes after the completion of the session, measurements of PWV and AIx@75 (normalized with heart rate 75 bpm) were obtained from each patient. Body composition was analyzed by bioimpedance spectroscopy device before and 30 minutes after completion of the hemodialysis session. During the hemodialysis, no significant change was observed in AIx@75. However, PWV decreased steadily during the session reaching statistically significant level at 135th minute (P = 0.026), with a maximal drop at 210th minute (P < 0.001). At 210th minute, decrease in PWV correlated positively with the decrease in central systolic blood pressure, central diastolic blood pressure, central pulse pressure, augmentation pressure, and AIx@75. Multiple regression analysis showed that decrease in PWV at 210th minute was associated with decrease in central systolic blood pressure and central pulse pressure. Ultrafiltration during hemodialysis had no significant effect on PWV and AIx@75. Delta urea correlated positively with delta PWV at 240th minute. A significant decrease in PWV was observed during hemodialysis and correlated with urea reduction; however, we were unable to document any effect of volume removal on arterial stiffness.     

Effects of frequent hemodialysis on blood pressure: Results from the randomized frequent hemodialysis network trials

Hypertension is a common complication of chronic kidney disease and persists among most patients with end‐stage renal disease despite the provision of conventional thrice weekly hemodialysis (HD). We analyzed the effects of frequent HD on blood pressure in the randomized controlled Frequent Hemodialysis Network trials. The daily trial randomized 245 patients to 12 months of 6× (“frequent”) vs. 3× (“conventional”) weekly in‐center hemodialysis; the nocturnal trial randomized 87 patients to 12 months of 6× weekly nocturnal HD vs. 3× weekly predominantly home‐based hemodialysis. In the daily trial, compared with 3× weekly HD, 2 months of frequent HD lowered predialysis systolic blood pressure by ?7.7 mmHg [95% confidence interval (CI): ?11.9 to ?3.5] and diastolic blood pressure by ?3.9 mmHg [95% CI: ?6.5 to ?1.3]. In the nocturnal trial, compared with 3× weekly HD, 2 months of frequent HD lowered systolic blood pressure by ?7.3 mmHg [95% CI: ?14.2 to ?0.3] and diastolic blood pressure by ?4.2 mmHg [95% CI: ?8.3 to ?0.1]. In both trials, blood pressure treatment effects were sustained until month 12. Frequent HD resulted in significantly fewer antihypertensive medications (daily: ?0.36 medications [95% CI: ?0.65 to ?0.08]; nocturnal: ?0.44 mediations [95% CI: ?0.89 to ?0.03]). In the daily trial, the relative risk per dialysis session for intradialytic hypotension was lower with 6×/week HD but given the higher number of sessions per week, there was a higher relative risk for intradialytic hypotensive requiring saline administration. In summary, frequent HD reduces blood pressure and the number of prescribed antihypertensive medications.     

Assessment of subjective and hemodynamic tolerance of different high‐ and low‐flux dialysis membranes in patients undergoing chronic intermittent hemodialysis: A randomized controlled trial

Clinical experience and experimental data suggest that intradialytic hemodynamic profiles could be influenced by the characteristics of the dialysis membranes. Even within the worldwide used polysulfone family, intolerance to specific membranes was occasionally evoked. The aim of this study was to compare hemodynamically some of the commonly used polysulfone dialyzers in Switzerland. We performed an open‐label, randomized, cross‐over trial, including 25 hemodialysis patients. Four polysulfone dialyzers, A (Revaclear high‐flux, Gambro, Stockholm, Sweden), B (Helixone high‐flux, Fresenius), C (Xevonta high‐flux, BBraun, Melsungen, Germany), and D (Helixone low‐flux, Fresenius, Bad Homburg vor der Höhe, Germany), were compared. The hemodynamic profile was assessed and patients were asked to provide tolerance feedback. The mean score (±SD) subjectively assigned to dialysis quality on a 1–10 scale was A 8.4 ± 1.3, B 8.6 ± 1.3, C 8.5 ± 1.6, D 8.5 ± 1.5. Kt/V was A 1.58 ± 0.30, B 1.67 ± 0.33, C 1.62 ± 0.32, D 1.45 ± 0.31. The low‐ compared with the high‐flux membranes, correlated to higher systolic (128.1 ± 13.1 vs. 125.6 ± 12.1 mmHg, P < 0.01) and diastolic (76.8 ± 8.7 vs. 75.3 ± 9.0 mmHg; P < 0.05) pressures, higher peripheral resistance (1.44 ± 0.19 vs. 1.40 ± 0.18 s × mmHg/mL; P < 0.05) and lower cardiac output (3.76 ± 0.62 vs. 3.82 ± 0.59 L/min; P < 0.05). Hypotension events (decrease in systolic blood pressure by >20 mmHg) were 70 with A, 87 with B, 73 with C, and 75 with D (P < 0.01 B vs. A, 0.05 B vs. C and 0.07 B vs. D). The low‐flux membrane correlated to higher blood pressure levels compared with the high‐flux ones. The Helixone high‐flux membrane ensured the best efficiency. Unfortunately, the very same dialyzer correlated to a higher incidence of hypotensive episodes.     

Effect of hemodiafiltration with endogenous reinfusion on overt idiopathic chronic inflammation in maintenance hemodialysis patients: A multicenter longitudinal study

Chronic inflammation is widely diffuse in maintenance hemodialysis (MHD) patients and is associated with poor survival. Hemodiafiltration with endogenous reinfusion (HFR) is a dialysis technique, highly biocompatible, able to adsorb proinflammatory cytokines and to decrease amino acids and antioxidants loss. These features could be helpful in MHD patients affected by idiopathic chronic inflammation, but this issue remains to be elucidated. We performed a multicenter longitudinal study to assess the effect of the switching from bicarbonate HD to HFR in patients with serum C‐reactive Protein (CRP) > 5 mg/L coupled with albumin <4.0 g/dL in the last 6 months. We enrolled 24/176 (14%) patients, of which 20 patients were assessed at 4 months and 18 completed the study. We excluded 11 patients with evident causes of inflammation. At baseline, serum levels of CRP (18.7[7.0–39.4] mg/L) and albumin (3.5[3.3–3.7] g/dL) were significantly correlated (r = ?0.49; P = 0.028). The effect on CRP and albumin was almost evident in the first 4 months and remained stable until to eighth month. A strict correlation (R = ?0.49; 0.040) between percentage change of CRP (?35%) and albumin (+14%) after 8 months of HFR. These effects were associated with the reduction of IL‐6, IL‐1β, and TNF‐α and the increment of pre‐albumin and leptin, whereas the serum levels of Branched Chain Amino Acid (BCAA) remained unchanged. In MHD patients affected by idiopathic chronic inflammation the switching from BHD to HFR is associated with improvement of inflammation. Whether these favorable effects may modify the outcomes of these high‐risk patients needs to be confirmed by studies ad hoc.