Short and long nightly hemodialysis in the United States

When hemodialysis first started in the United States in the 1960s, a large percentage of patients performed their treatments at home. However, because of reimbursement issues, home hemodialysis (HHD) gradually succumbed to an in-center approach and eventually a mindset. Since the introduction of nightly HHD by Uldall and Pierratos in 1993, there has been a resurgence of interest in HHD. This paper describes the different types of home hemodialysis being performed as of December 31, 2007 in this country. Because neither the United States Renal Data System (USRDS) nor the End Stage Renal Disease (ESRD) Networks break down home dialysis into the different modalities, a provider questionnaire was sent out to 2 major providers, a number of mid-level providers and other providers known to do HHD. In addition, a questionnaire was sent out to 3 machine providers to obtain the number of patients using their machine for HHD as of December 31, 2007. The results showed that 91.7% of patients are dialyzing in-center, 7.3% are doing peritoneal dialysis, and 0.7% are doing HHD. Currently about 1% of ESRD patients in the United States are doing home hemodialysis. NxStage, however, has started 1000 patients in the past year on short-daily home hemodialysis. Patients are beginning to understand that there are better options than 3 times a week in-center dialysis. And as a result of the "HEMO Study," nephrologists now believe that longer and more frequent dialysis is a better therapy for ESRD patients. Therefore, promotion of HHD should become a priority for the renal community in the future.     

Use of 3‐hour daily hemodialysis and paricalcitol in patients with severe secondary hyperparathyroidism: A case series

Patients with poor metabolic control receiving conventional hemodialysis are at risk for developing severe secondary hyperparathyroidism. We postulated that daily hemodialysis may be effective at controlling parathyroid hormone (PTH) in the setting of severe secondary hyperparathyroidism by improving the control of hyperphosphatemia and allowing increased use of vitamin D analogs. We present 5 patients with severe secondary hyperparathyroidism (median iPTH=1783 pg/mL) who were treated with 3‐hour daily hemodialysis (3 hours × 6 times a week). Daily hemodialysis, at 1 year, was associated with a 70.4% reduction in median PTH (1783 pg/mL [interquartile range: 1321–1983]–472 pg/mL [334, 704], P<0.001). Additionally, there was an increase in paricalcitol dose from 0 mcg/d to 10.8 (2.00, 11.7) mcg/d, a 39% reduction in calcium × phosphorus product (80.3 ± 26.8–48.9 ± 14.0, P<0.01), a 52% reduction in serum phosphorus (9.90 ± 2.34–4.75 ± 0.79 mg/dL, P<0.0001), and a 17.6% increase in serum calcium (8.18 ± 2.04–9.62 ± 0.93 mg/dL, P<0.01). Three‐hour daily hemodialysis with the use of high‐dose paricalcitol is associated with improved control of severe secondary hyperparathyroidism.     

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.     

Plasma myeloperoxidase,NT‐proBNP,and troponin‐I in patients on CAPD compared with those on regular hemodialysis

Myeloperoxidase (MPO) is a hemoprotein that is released during inflammation and may lead to irreversible protein and lipid modification, increasing levels of oxidized low density lipoprotein, and promoting athrogenesis. Recently, it has been considered as a risk factor for cardiovascular diseases. Similarly, the measurement of carotid intima‐media thickness gives an indication about the degree of atherosclerosis and prediction of clinical cardiovascular events. Elevated white blood cells counts may indicate a state of acute inflammation and follow its progression. Dialysis patients are at a high risk of developing cardiovascular disease compared with healthy subjects. The role of N‐terminal pro‐brain natriuretic peptide and increased cardiac troponin in identification and prognostication of cardiovascular diseases in end‐stage renal disease patients has been investigated. The current study aimed to evaluate plasma MPO and its possible relationship with carotid intima‐media thickness, troponin I, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and insulin resistance as measured by homeostatic model assessment (HOMA index) in a cohort of Saudi patients who are undergoing hemodialysis (HD) vs. continuous ambulatory peritoneal dialysis for end‐stage renal disease. Plasma MPO was significantly higher in patients on continuous ambulatory peritoneal dialysis (CAPD) than in those on HD and in normal subjects (P<0.001). Conversely, NT‐proBNP plasma levels were significantly higher in patients on HD (both predialysis and postdialysis) than in those on CAPD (P<0.01) and than normal subjects. Similarly, plasma troponin‐I levels were significantly higher in patients on HD compared with those of CAPD and than normal subjects (P<0.001). Plasma troponin‐I and NT‐proBNP levels were positively correlated in the 3 groups namely those on CAPD, Pre‐HD, and post‐HD (r: 0.464 and P=0.047; r: 0.330 and P=0.013; and r: 0.452 and P=0.024), respectively. There was no correlation between the MPO level and carotid intima‐media thickness (P>0.05). However, plasma MPO level correlated positively with the white blood cell count in patients on CAPD and in those on HD (P<0.05). Our findings suggest an increased oxidative stress in CAPD patients compared with HD patients, while the reported difference in plasma NT‐proBNP and troponin‐I may be related to the rapid decline of residual renal function in HD and type of membrane used in the HD dialysis procedure itself.     

Confounding factors for early death in incident end‐stage renal disease patients: Role of emergency dialysis start

Hemodialysis (HD) has been associated with higher 1‐year mortality than peritoneal dialysis (PD) after dialysis start. Confounding effects of late referral, emergency dialysis start, or start with central venous catheter on this association have never been studied concomitantly. Survival was studied among the 495 incident dialysed patients in our department from 1995 to 2006 and followed at least 1 year until December 31, 2007. Nested Cox models adjusted on patient characteristics explored factors associated with 1‐year and ≥1‐year mortality. Hemodialysis patients were 332 (67.1%), 104 (21.0%) were late referred (<6 months), 167 (33.7%) started dialysis in emergency, and 144 (29.1%) started with central venous catheter. When adjusted only on age, sex, and comorbidities, HD was associated with poor 1‐year outcome: adjusted hazard ratio (aHR) for death in HD vs. PD was 1.77, P=0.02. In fully adjusted model, among first dialysis feature variables, only emergency dialysis start was significantly associated with 1‐year mortality: aHR 1.53, P=0.02. Dialysis modality was not associated with 1‐year mortality rates in this fully adjusted model: aHR in HD vs. PD became 1.03, P=0.91. In ≥1‐year period, HD was associated with lower mortality than PD (aHR 0.61, P=0.004), whereas other first dialysis features were not associated with death. Other factors associated with death were age, type 2 diabetes, peripheral vascular disease, heart failure, and hepatic failure. Negative association between HD and 1‐year survival on dialysis was explained by confounders. Emergency dialysis start was strongly associated with early mortality on dialysis. Its prevention may improve patient survival.     

High‐dose cefazolin on consecutive hemodialysis in anuric patients with Staphylococcal bacteremia

Methicillin‐sensitive Staphylococcus aureus (MSSA) bacteremia is a leading cause of infection in hemodialysis (HD) patients. Cloxacillin, cefazolin, and vancomycin are the mainstay antimicrobials. Cloxacillin administration leads to frequent drug dosing, longer length of stay (LOS), and higher cost, while resistance and poorer outcomes are associated with vancomycin use. Dosing cefazolin during HD allows for prolonged blood therapeutic levels. We assessed the outcomes and safety of a strategy of treating MSSA bacteremia with 2–3 g cefazolin on HD only. All HD patients with MSSA bacteremia admitted in June–December 2009 at our center and receiving this regime were compared with historical controls who received cloxacillin. Demographic characteristics and outcome measures like mortality, LOS, cost, recrudescence, and adverse drug reactions were assessed. Of 27 consecutive episodes reviewed, 14 and 13 patients received cefazolin and cloxacillin, respectively. Baseline demographics were comparable between the 2 treatment groups. More than one‐third of the bacteremia was related to tunneled catheter infection. The 30‐day mortality of cloxacillin‐ and cefazolin‐treated patients was 15% and 7%, respectively (P=0.14). Two of the 11 survivors treated with cloxacillin (18%) had recrudescent bacteremia while none was observed in cefazolin‐treated survivors. Cefazolin was associated with shorter LOS (10 vs. 20 days, P<0.05) and lower cost (US$8262.00 vs. US$15,367.00, P<0.05). Cefazolin use resulted in 3 idiosyncratic adverse drug reactions. Cefazolin dosed on each HD in MSSA bacteremia leads to earlier discharge and less cost. Larger prospective studies are, however, warranted to fully assess its safety and efficacy.     

The renaissance of home hemodialysis: where we are, why we got here, what is happening in the United States and elsewhere

Home hemodialysis has been around since 1964, but its use has declined over the years in most countries, this despite its advantages, particularly improved patient survival and quality of life and significant cost savings. Experience has shown that home hemodialysis can be performed successfully by many more patients than at present. Recently, with the demonstration of even better results with more frequent hemodialysis that is obviously best performed at home and with the development of new, more patient-friendly machines, the use of home hemodialysis is beginning to increase again.     

Costs of managing anemia with erythropoiesis‐stimulating agents during hemodialysis: A time and motion study

Use of erythropoiesis‐stimulating agents (ESAs) presents a significant time and cost burden in the management of anemia of chronic kidney disease (CKD). We conducted a prospective, observational, activity‐based costing study to estimate the health care personnel time and resulting direct medical costs associated with administering epoetin 3 times weekly to patients with end‐stage renal disease on dialysis. The study was conducted at 5 US hemodialysis centers. The personnel time and costs were derived from time and motion observations. Predicted time and cost savings were modeled for switching patients to once‐monthly ESA therapy. Patients also completed a survey questionnaire to assess their level of CKD knowledge and information needs. Total per‐patient‐per‐year (PPPY) time expended on anemia management with epoetin averaged 608 minutes (range 512–915 minutes), with an average PPPY cost of $548 (range $342–$651). Use of a once‐monthly ESA, compared with epoetin, could decrease average PPPY time expenditure by 79% (127 minutes [range 96–173 minutes]) and reduce PPPY costs by 81% ($104 [range $79–$136]). The patient questionnaire reported insufficient education on CKD. Use of a once‐monthly ESA to correct anemia in dialysis patients may provide substantial time, resource, and cost savings compared with current treatment practices.     

Association of mineral metabolism factors with all-cause and cardiovascular mortality in hemodialysis patients: the Japan dialysis outcomes and practice patterns study

Abnormalities in mineral metabolism have been linked to mortality in hemodialysis (HD) patients. We postulated that these abnormalities would have a particularly large deleterious impact on deaths due to cardiovascular causes in Japan. This study describes the recent status of abnormal mineral metabolism, significant predictors, and potential consequences in the Dialysis Outcomes and Practice Patterns Study (DOPPS), Phases 1 and 2, in Japan. Major predictor variables were patient demographics, comorbidities, and laboratory markers of mineral metabolism such as albumin-adjusted serum calcium (calciumAlb), phosphorus, and intact PTH (iPTH). In a cross section of 3973 Japanese HD patients in DOPPS I and II, a large faction had laboratory values outside of the recommended Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline range for serum concentrations of phosphorus (51% of patients above upper target range), calciumAlb (43.7% above), calcium-phosphorus (Ca x P) product (41.1% above), and iPTH (18.6% above). All-cause mortality was significantly and independently associated with calciumAlb (relative risk [RR]=1.22 per 1 mg/dL, p=0.0005) and iPTH (RR=1.04 per 100 pg/mL, p=0.04). Cardiovascular mortality was significantly associated with calciumAlb (RR=1.28, p=0.02), phosphorus (RR=1.13 per 1 mg/dL, p=0.008), Ca x P product (RR=1.07 per 2 mg(2)/dL(2), p=0.002), and PTH (RR=1.08, p=0.0001). This study expands our understanding of the relationship between altered mineral metabolism and mortality outcomes, showing slightly stronger associations with cardiovascular causes than observed for all-cause mortality. These findings have important therapeutic implications for Japanese HD patients.     

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.     

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.     

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.     

The individually optimized bolus dose of nadroparin is safe and effective in diabetic and nondiabetic patients with bleeding risk on hemodialysis

The risk of bleeding is a well‐known complication in patients on hemodialysis (HD). The aim of this prospective study was to determine the lowest single bolus dose of low–molecular‐weight heparin nadroparin for safe and effective HD in patients with a bleeding risk. Forty HD patients were divided into 4 subgroups with 10 participants (diabetics with and without a bleeding risk, nondiabetics with and without a bleeding risk). The actual starting bolus dose was decreased by 25% after the initial 4 weeks, further decreased by 25% of the starting dose after 4 weeks, and changed due to extracorporeal circuit clotting in the last 4 weeks. The parameters of coagulation were measured at the beginning, after 2 and 4 h of HD sessions. A significant reduction of nadroparin (first vs. last HD session) was observed in: diabetics with a bleeding risk (49.66 ± 12.33 vs. 28.78 ± 9.60 IU/kg/HD; P<0.001), diabetics without a bleeding risk (50.70 ± 15.23 vs. 33.95 ± 16.97 IU/kg/HD; P<0.001), and nondiabetics with a bleeding risk (61.25 ± 18.68 vs. 32.96 ± 10.06 IU/kg/HD; P<0.001). Altogether, the reduction of the nadroparin dose in these groups was 42.05%; 33.04%, and 46.19%, respectively. Although anti‐Xa at hour 4 at the end of the study was <0.4 IU/mL in our diabetic and nondiabetic patients without a risk of bleeding, serious clottings in the extracorporeal circuit and vascular access thromboses were not found. This study demonstrated for the first time that individually optimized doses of nadroparin are sufficient for safe and effective HD in patients with a bleeding risk.     

Clinical epidemiology of parathyroidectomy in hemodialysis patients: the USRDS waves 1, 3, and 4 study

Despite advances in the medical management of secondary hyperparathyroidism, parathyroidectomy remains necessary in some end-stage renal disease patients. Observational studies may help with the design of intervention trials. We linked the retrospective Waves 1, 3, and 4 Dialysis Morbidity and Mortality Study datasets to Medicare claims data to identify incident parathyroidectomy in 10,588 Medicare patients receiving hemodialysis in the United States on December 31, 1993. The mean age was 60.0 years, and the mean follow-up 3.6 years. De novo parathyroidectomy incidence was 14.2/1000 patient-years. Considered as quintiles (Q), higher levels of standard bone metabolism variables were associated (p<0.0001) with parathyroidectomy stepwise, such that adjusted hazards ratios (AHR) for Q5 (vs. Q1) were, for calcium (>10.3 mg/dL), 5.09 (3.64-7.10); for phosphorus (>7.5 mg/dL), 2.92 (2.06-4.15); for calcium-phosphorus product (>71 mg2/dL2), 3.32 (2.27-4.85); and for parathyroid hormone (PTH; >480 pg/mL), 13.81 (7.47-25.55). Other antecedent associations included younger age, lower hemoglobin, and longer dialysis vintage, while transplantation, as a time-dependent covariate, was associated with lower hazards ratios. Using interval Poisson analysis, parathyroidectomy was associated with higher mortality risk ratios in the first year, and progressively lower risk ratios subsequently. Demographic variables may modify the risk of parathyroidectomy. Younger patients on long-term hemodialysis may be at a special risk. Parathyroidectomy risk increases stepwise with alterations in bone metabolism variables, suggesting that a single-threshold management approach may not be ideal.     

Comparison of serum albumin,C‐reactive protein and carotid atherosclerosis as predictors of 10‐year mortality in hemodialysis patients

Serum albumin, C‐reactive protein (CRP), and the intima‐medial thickness of the common carotid artery (CA‐IMT) are associated with clinical outcomes in hemodialysis (HD) patients. However, it remains unclear which parameters are more reliable as predictors of long‐term mortality. We measured serum albumin, CRP, and CA‐IMT in 206 HD patients younger than 80 years old, and followed them for the next 10 years. One hundred sixty‐eight patients (age: 57 ± 11 years, time on HD: 11 ± 7 years) were enrolled in the analyses. We divided all patients into three tertiles according to their albumin levels, and conducted multivariate analyses to examine the impact on 10‐year mortality. Seventy‐three (43.5%) patients had expired during the follow‐up. Serum albumin was significantly lower in the expired patients than in the surviving patients (3.8 ± 0.3 vs. 4.0 ± 0.3, P<0.01), while CRP (4.7 ± 5.0 vs. 2.8 ± 3.5 g/L, P=0.01) and CA‐IMT (0.70 ± 0.15 vs. 0.59 ± 0.11 mm, P<0.01) were significantly higher in the expired group. The multivariate analysis revealed that there was a significantly higher risk for total mortality in HD patients with serum albumin <3.8 g/dL (odds ratio 5.04 [95% CI: 1.30–19.60], P=0.02) when compared with those with albumin >4.1 g/dL. In contrast, CRP and CA‐IMT did not associate with total death. It follows from these findings that serum albumin is more superior as a mortality predictor compared with CRP and CA‐IMT in HD patients.     

On stability and reflection‐transmission analysis of the bipenalty method in contact‐impact problems: A one‐dimensional,homogeneous case study

The stability and reflection‐transmission properties of the bipenalty method are studied in application to explicit finite element analysis of one‐dimensional contact‐impact problems. It is known that the standard penalty method, where an additional stiffness term corresponding to contact boundary conditions is applied, attacks the stability limit of finite element model. Generally, the critical time step size rapidly decreases with increasing penalty stiffness. Recent comprehensive studies have shown that the so‐called bipenalty technique, using mass penalty together with standard stiffness penalty, preserves the critical time step size associated to contact‐free bodies. In this paper, the influence of the penalty ratio (ratio of stiffness and mass penalty parameters) on stability and reflection‐transmission properties in one‐dimensional contact‐impact problems using the same material and mesh size for both domains is studied. The paper closes with numerical examples, which demonstrate the stability and reflection‐transmission behavior of the bipenalty method in one‐dimensional contact‐impact and wave propagation problems of homogeneous materials.