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.     

Reduction of carbamylated albumin by extended hemodialysis

Introduction Among conventional hemodialysis (CHD) patients, carbamylated serum albumin (C‐Alb) correlates with urea and amino acid deficiencies and is associated with mortality. We postulated that reduction of C‐Alb by intensive HD may correlate with improvements in protein metabolism and cardiac function. Methods One‐year observational study of in‐center nocturnal extended hemodialysis (EHD) patients and CHD control subjects. Thirty‐three patients receiving 4‐hour CHD who converted to 8‐hour EHD were enrolled, along with 20 controls on CHD. Serum C‐Alb, biochemistries, and cardiac MRI parameters were measured before and after 12 months of EHD. Findings EHD was associated with reduction of C‐Alb (average EHD change ?3.20 mmol/mol [95% CI ?4.23, ?2.17] compared to +0.21 [95% CI ?1.11, 1.54] change in CHD controls, P < 0.001). EHD was also associated with increases in average essential amino acids (in standardized units) compared to CHD (+0.38 [0.08, 0.68 95%CI]) vs. ?0.12 [?0.50, 0.27, 95% CI], P = 0.047). Subjects who reduced C‐Alb more than 25% were found to have reduced left ventricular mass, increased urea reduction ratio, and increased serum albumin compared to nonresponders, and % change in C‐Alb significantly correlated with % change in left ventricular mass. Discussion EHD was associated with reduction of C‐Alb as compared to CHD, and reduction of C‐Alb by EHD correlates with reduction of urea. Additional studies are needed to test whether reduction of C‐Alb by EHD also correlates with improved clinical outcomes.     

The advantages and disadvantages of home hemodialysis

In Australia, 12% of the hemodialysis population dialyze at home. Until recently, the majority of these patients dialyzed for similar hours to those in satellite dialysis. However, in the past 5 years there has been a new departure such that in many centers the concept of home hemodialysis is now synonymous with extended hours dialysis. Registry data supports the concept that increased frequency and duration of dialysis may result in improved patient survival and a reduction in cardiovascular risk profile. It is hoped, therefore, that the long recognized survival benefit observed in home hemodialysis patients may be further augmented by the swing to extended hours dialysis in this patient population. In addition to the physiological benefits of extended hours home dialysis, there are clear quality of life, social, and economic advantages associated with dialyzing at home. There are however a number of perceived disadvantages to home hemodialysis including the application and time commitment required for training, the potential for relationship strain or "burnout," and reluctance to "hospitalize" the home. Overall, however, in this new era of extended hours dialysis, the advantages both physiological and lifestyle of home hemodialysis far outweigh the disadvantages.     

Weekly high‐dose ergocalciferol to correct vitamin D deficiency/insufficiency in hemodialysis patients: A pilot trial

Controversy exists on which vitamin D (D2 or D3) and which dosage scheme is the best to obtain and maintain adequate 25 OH D levels in dialysis patients safely. We tried to determine whether high‐dose vitamin D2 supplementation could obtain optimal vitamin D status without inducing hypercalcemia. We studied 82 patients on dialysis not taking active vitamin D therapy and supplemented them with oral vitamin D2 72,000 IU/week for 12 weeks followed by 24,000 IU/week as maintenance therapy during 36 weeks. By week 12, serum 25(OH)D increased from 15.2 ± 5.4 to 42.5 ± 13.2 ng/mL (P < 0.01) at week 12 and remained optimal (34.7 ± 12.0); 84.8% of the patients reached values ≥30 ng/mL. iPTH and alkaline phosphatase did not change at 48 weeks compared with baseline, but bone alkaline phosphatase decreased significantly (54.3 ± 46.0 to 44.3 ± 25.0; P = 0.02). Uncorrected serum Ca increased significantly at the end of follow‐up (9.03 ± 0.42 to 9.14 ± 0.62; P = 0.04); hypercalcemia was presented in two patients in the first control visit (week 12), in one patient in the second control (week 30), and in one patient in the third control (week 48). In 222 serum calcium determinations during follow‐up, hypercalcemia was observed in only 1.8% of cases. This vitamin D2 oral regimen with initial high doses was safe and sufficient to obtain and maintain optimal serum 25(OH)D concentrations and prevent vitamin D insufficiency in chronic kidney disease patients on dialysis.     

Time‐extended local rtPA infiltration for acutely thrombosed hemodialysis fistulas

Introduction: This study describes results of a modified local thrombolysis technique for acutely thrombosed hemodialysis (HD) arteriovenous fistulas (AVF), which is characterized by prolonged recombinant tissue plasminogen activator (rtPA) local exposure times. Contrary to the standard lyse‐ and‐ wait (L&W) technique with local reaction times of 20–40 minutes, the modified protocol allows timing of challenging angioplasty maneuvers to the next regular working day. Methods: From February 2009 to April 2014, 84 patients on HD presented with 152 acutely thrombosed AVF. They proceeded to local thrombolysis including a single shot infiltration of rtPA, local reaction time up to 40 hours and finally percutaneous stenosis angioplasty. Success rates, major adverse events and need for temporary catheter placements (TCP) were retrospectively analyzed. Findings: The local thrombolysis time after single shot infiltration was 18.6 ± 6.2 (range 2–40) hours. Mean rtPA‐ dosage was 2.7 mg ± 1.2. The overall success rate was 89.5% and the major complication rate was 3.3%, whereas TCP was necessary in 12.5%. The PP/SP at 1, 3, 6, 12, 18, and 24 month were 86% ± 3%/95% ± 2%, 68% ± 4%/92% ± 2%, 43% ± 4%/90% ± 2%, 28% ± 4%/82% ± 3%, 12% ± 3%/82% ± 3%, 7% ± 2%/63% ± 4%, respectively. Conclusion: The modified L&W technique with prolonged local rtPA reaction times is a safe and effective declotting procedure. The need for TCP was not increased and therefore comparable to the standard technique.     

Road safety impact of extended drinking hours in Ontario

PURPOSE: On 1 May 1996, Ontario, Canada amended the Liquor Licence Act to extend the hours of alcohol sales and service in licensed establishments from 1 to 2 a.m. The purpose of this study was to evaluate the road safety impact of extended drinking hours in Ontario. METHOD: A quasi-experimental design using interrupted time series with a nonequivalent no-intervention control group was used to assess changes. The analyzed data sets are total and alcohol-related, monthly, traffic fatalities for Ontario, for the 11-12 p.m., 12-1 a.m., 1-2 a.m. and 2-3 a.m. time windows, for Sunday through Wednesday nights and for Thursday through Saturday nights, for 4 years pre- and 3 years post-policy change, compared to neighbouring regions of New York and Michigan. RESULTS: The blood alcohol concentration positive driver fatality trends reflected downward trends for Sunday-Wednesday 12-2 a.m. and Thursday-Saturday 1-2 a.m. for Ontario and downward trends for Thursday-Saturday 12-1 a.m. and 2-3 a.m. for New York and Michigan after the extended drinking hour policy change. Ontario total fatality data showed similar trends to the Ontario blood alcohol positive trends. CONCLUSIONS: The multiple datasets converge in suggesting little impact on BAC positive fatalities with extension of the closing hours. These observations are consistent with other studies of small changes in alcohol availability.     

Cloxacillin‐induced seizure in a hemodialysis patient

We are reporting a cloxacillin‐induced seizure in a patient with stage 5 chronic kidney disease requiring hemodialysis. To our knowledge, there are no published case reports of seizures induced by parenteral cloxacillin in hemodialysis patients. A young hemodialysis female was admitted to the hospital with decreased level of consciousness. Blood cultures revealed methicillin‐sensitive Staphylococcus aureus where cloxacillin 2 g intravenously every 4 hours was initiated. Head computed tomography (CT) was not significant. After 14 hours of cloxacillin therapy (4 doses), the patient demonstrated tonic/clonic seizure activity, where phenytoin and lorazepam were initiated. The anti‐seizure medications partially reduced seizure activity. Once the cloxacillin was discontinued, the seizures stopped. Two weeks later, all anti‐seizure medications were stopped with no further seizure activity. Cloxacillin elimination in hemodialysis patients is similar to patients with normal kidney function. Although cloxacillin does not significantly cross the blood–brain barrier, the correlation between the start of seizures and cloxacillin initiation was confirmed by the negative CT and blood chemistry laboratory results. Moreover, seizure activity was terminated upon discontinuation of cloxacillin. Although further investigation for the cause of such seizures is warranted, clinicians should use caution when giving high doses of cloxacillin in hemodialysis patients.     

Association of low vitamin D levels with metabolic syndrome in hemodialysis patients

Low vitamin D levels have been linked to metabolic syndrome in the general population. In the present study, the relationship between inadequate serum concentrations of vitamin D and metabolic syndrome in patients with end‐stage renal disease undergoing hemodialysis was explored. In a cross‐sectional setting, 145 patients undergoing maintenance hemodialysis were enrolled. Metabolic syndrome was defined using the International Diabetes Federation criteria. Serum concentration of 25(OH) vitamin D was determined by a commercially available enzyme immunosorbent assay method. The prevalence of metabolic syndrome was 53.1%. The prevalence rate of severe vitamin D deficiency (<5 ng/mL) was 3.4%, mild vitamin D deficiency (5–15 ng/mL) 31.0%, vitamin D insufficiency (16–30 ng/mL) 36.6%, and vitamin D sufficiency (>30 ng/mL) 29.0%. With the increasing number of metabolic abnormalities, vitamin D levels significantly decreased (P for trend = 0.028). Among the components of metabolic syndrome, vitamin D deficiency was significantly associated with central obesity (odds ratio [OR], 95% confident interval [CI] = 2.80, 1.11–7.04, P = 0.028). A positive, but nonsignificant association between vitamin D deficiency and raised fasting plasma glucose was noted (OR, 95% CI = 2.40, 0.94–6.11, P = 0.067). Both vitamin D deficiency and insufficiency were significantly associated with an increased likelihood of having metabolic syndrome (P < 0.05). In a final model controlling for age, sex, and parathyroid hormone levels, vitamin D deficiency increased the odds of having metabolic syndrome by more than threefold (OR, 95% CI = 3.26, 1.30–8.20, P = 0.012). Low levels of vitamin D are frequent among hemodialysis patients and are associated with the metabolic syndrome.     

Prevalence of 25(OH) vitamin D insufficiency and deficiency in chronic kidney disease stage 5 patients on hemodialysis

Little is known about the magnitude of vitamin D deficiency in patients with stage 5 chronic kidney disease (CKD-5) on hemodialysis (HD). In the present study, we examined the prevalence of vitamin D deficiency in patients with CKD-5 undergoing HD, evaluating the relationship between calcidiol levels with other parameters of mineral metabolism, nutrition/inflammation, functional capacity (FC), and sunlight exposure. Serum 25(OH) vitamin D levels were evaluated in 84 stable patients on chronic HD not receiving vitamin D supplements, with a mean age 58.9+/-16.6 years, during the month of September (end of winter in the southern hemisphere). 25(OH) vitamin D serum levels, intact PTH (iPTH), as well as serum albumin, calcium, phosphorus, and alkaline phosphatase were analyzed in fasting samples. Similarly, protein catabolic rate (PCR) and body mass index (BMI) were determined as nutritional parameters. Functional capacity according to the Karnofsky index, and sunlight exposure were also analyzed. In this study, we considered adequate vitamin D levels those above 30 ng/mL (U.S.A. National Kidney Foundation DOQI Guidelines), vitamin D insufficiency when levels were between 15 and 30 ng/mL, and vitamin D deficiency when levels were below 15 ng/mL. The mean 25(OH) D levels were significantly higher in men than in women (28.6 vs. 18.9 ng/mL; p=0.001). Vitamin D insufficiency was found in 53.5% of the patients (n=45) and vitamin D deficiency in 22.6% (n=19). In the univariate analysis, there were no correlations between 25(OH) D levels with age, iPTH, calcium, or phosphorus. There were positive correlations between serum 25(OH) D levels and degrees of sunlight exposure (R=0.55; p<0.0001), serum creatinine (r=0.38; p<0.001), serum albumin (r=0.22; p=0.04), and a negative correlation with BMI (r=-0.26; p=0.01). In the multiple regression analysis, only sunlight exposure (B=0.361), BMI (B=-0.23), and gender (B=-0.27) were significantly associated with 25(OH) D levels. Patients with FC 1 to FC 2 (n: 70%, 83.3%) had significantly higher 25(OH) D serum levels compared with FC 3 to FC 4 patients (n: 14%, 16.6%): 25.9 vs. 17.1 ng/mL (p=0.03). These results indicate that vitamin D insufficiency/deficiency is highly prevalent (76.1%) at the end of winter, in stage 5 CKD patients on HD, and lower values seem to be related to decreased sunlight exposure, female gender, increased BMI, and worse functional class.     

Nightly home hemodialysis: outcome and factors associated with survival

Nightly home hemodialysis (NHHD) has been reported to have a much better survival than the excessive mortality of thrice-weekly in-center dialysis, but the factors influencing survival of NHHD have not been investigated in detail. We studied the association of survival in a 12-year study of 87 NHHD patients from a single center evaluating demographic, sociologic, and anthropomorphic factors, diagnosis, comorbidity, vintage, and dialysis performance and efficiency. Secondly, we compared the survival of the 87 NHHD patients with that reported by the United States Renal Data System (USRDS) using standardized mortality rate (SMR). The average patient age was 52 ± 15 years, and 59% were males, 51% African Americans, and 25% had diabetes. The patients dialyzed 40 ± 6 hours weekly with a stdKt/V of 5.25 ± 0.84. Thirteen patients died. The cumulative survival was 79% at 5 years and 64% at 10 years. Using Cox proportional hazards univariate analysis, 7 of 26 factors studied were associated with mortality: less than high school education, hour of each dialysis, comorbidities, secondary renal disease, congestive heart failure, Leypoldt's eKt/V, and Daugirdas Kt/V. In backward stepwise Cox analysis, education and hour of dialysis were the only factors independently associated with survival. The standardized mortality rate was only 0.30 of that reported by the United States Renal Data System for patients on thrice-weekly hemodialysis adjusted for age, gender, race, and diagnosis. The influence of education was the most significantly associated with survival, and the duration of each dialysis treatment was important. The survival rate of NHHD patients appeared to be superior to intermittent hemodialysis.     

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.     

Catheter‐related bacteremia and mortality in frequent nocturnal home hemodialysis

Frequent nightly home hemodialysis (NHHD) has emerged as an attractive alternative to thrice weekly in‐center hemodialysis, albeit with preponderant long‐term hemodialysis catheter used. Sixty‐three NHHD patients from University of Virginia Lynchburg Dialysis Facility were matched 1:2 with 121 conventional hemodialysis patients admitted to Fresenius Medical Care North America facilities from January 1, 2007 to December 31, 2010. Matching considered age (± 5 years), gender, race, dialysis vintage, and diabetes. The primary end‐point was the combined incidence of bacteremia/sepsis, for up to 20 months or upon changing to a fistula/graft (with catheter removal), transferring to peritoneal dialysis (PD), or at the time of kidney transplant or death. No significant differences were observed in rate of fistula/graft conversion, transfer to PD, transplant, or death between NHHD and in‐center hemodialysis (IHD) groups. For the first catheter used, the rate of catheter‐related sepsis was not significantly different between the NHHD (1.77 per 100 patient months) and IHD (2.03 per 100 patient months; P = 0.21). Combining all catheters, the rate of bacteremia/sepsis per 100 patient months in the NHHD group was 1.51 and in the IHD group was 2.01 (P = 0.35). Median catheter lifespan for the first catheter was 5.6 (1.7～19.0) for NHHD and 4.6 (2.7～7.8) for the IHD group (P = 0.64), and for all catheters used was 5.2 (Q1～Q3 = 1.5～15.2) months in NHHD group, and 4.1 (2.0～6.8) months in IHD group (P = 0.20). The rate of bacteremia and death is not different for up to 20 months in catheter users who dialyze via frequent NHHD vs. thrice weekly IHD.     

Comparison of intradialytic blood pressure variability between conventional thrice‐weekly hemodialysis and short daily hemodialysis

Intradialytic blood pressure (BP) variability may be associated with increased mortality. We examined the effect of short daily hemodialysis (SDHD) on intradialytic BP variability relative to conventional thrice‐weekly HD (CHD). This is a retrospective cohort study. Subjects were those converted from CHD to SDHD (n=12). All intradialytic BPs were collected on the last month of CHD, and on month 6 of SDHD. Absolute predialysis BP level and intradialytic BP variability were defined as the intercept and average residual terms, respectively, from a mixed‐effects linear regression model of time on BP. Dialysis modality was a predictor variable (CHD vs. SDHD). Outcome variables were intradialytic BP variability and hypotension (BP<90/55 mmHg at any time during HD). In addition to a predictor and outcomes, the demographics, estimated dry weight, and ultrafiltration ratio were examined. The median (range) age of the patients was 48 (34–77); all had hypertension, and 4 (33%) had diabetes. By a mixed effects linear regression model, the intradialytic systolic BP variability was 13.2 (quartile range 9.5–14.0) mmHg and 10.0 (8.3–10.9) mmHg for CHD and SDHD, respectively (P<0.006). Intradialytic diastolic BP variability was also significantly reduced (7.7 [6.4–9.2] vs. 6.1 [5.5–6.6] mmHg, P=0.005). Relative to CHD, less hypotension was observed during treatment on SDHD: the odds ratio (95% confidence interval) was 0.36 (0.16–0.81; P=0.008). In this retrospective study, SDHD was associated with less intradialytic BP variability and with fewer episodes of hypotension during treatments. Further studies are necessary to generalize these findings.     

Patient mood flux on‐ and off‐hemodialysis

Mood in hemodialysis patients is most often evaluated off‐dialysis, possibly underestimating mood during dialysis. We compared mood in patients on‐ and off‐dialysis using the Positive and Negative Affect Schedule for 6 consecutive days. Initially, scores are normal, but subsequently positive affect falls below, and negative affect increases above, off‐dialysis values, suggesting increasing depression and anxiety, particularly in women. Quality‐of‐life questions confirm the effects of the dialysis session on mood. Prevalence and severity of depression evaluated off‐dialysis, or once only, may be underestimated, especially in women, because hemodialysis patients undergo mood swings centering on the dialysis session. Focusing insight on the dialysis session could improve coping among patients and caretakers.     

Perihospitalization patterns of hemoglobin levels and erythropoiesis‐stimulating agent doses in US hemodialysis patients, 1998–2009

Anemia management in hemodialysis patients is of primary importance for clinicians and dialysis providers. Through a retrospective claims analysis, we studied prevalent US hemodialysis patients 1998–2009, and examined patterns of hemoglobin levels and erythropoiesis‐stimulating agent (ESA, epoetin [EPO], and darbepoetin [DPO] ) doses surrounding hospitalization events. Medicare outpatient claims were used to determine monthly ESA doses and associated hemoglobin levels. ESA dose trajectories were defined with repeated measures models incorporating an autoregressive covariance matrix that compared subsequent measurements with the index month of hospitalization, with variance component covariance matrices chosen for pair‐wise comparisons. Regarding prehospitalization hemoglobin levels, a biphasic pattern occurred in both the EPO (1998–2009, n = 161,242) and DPO (2004–2009, n = 4391) populations; levels rose from 1998 to 2004, fell thereafter in the EPO population, and fell after 2006 or 2007 in the DPO population. In the EPO population, the proportions of patients with hemoglobin less than 10 g/dL were 30.1% in 1998, 14.5% in 2004, and 28.3% in 2009; corresponding values for the DPO population were 21.0% in 2004 and 31.6% in 2009. While some degree of year‐to‐year variability occurred, EPO dose trends were less pronounced, with an apparent peak in 2004 followed by a modest decline; trends were similar for DPO. Trends in EPO dose trajectories did not completely parallel those for hemoglobin level; while EPO doses increased yearly up to 2004, doses stabilized, but did not materially decrease after 2004. No definite annual trends for DPO dose trajectories were apparent.     

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.