Dialysis patients treated with Epoetin alfa show improved anemia symptoms: A new analysis of the Canadian Erythropoietin Study Group trial

The health‐related quality of life (HRQOL) claims in the current Epoetin alfa label are based on the reanalyses of the exercise and physical function data from the Canadian Erythropoietin Study Group trial. The reanalysis was done to comply with the Food and Drug Administration's requirement of using statistical methods that are currently standard in evaluating clinical trial data. Presented here are HRQOL results associated with anemia. The Canadian Erythropoietin Study Group trial was a multicenter, double blind, randomized, placebo‐controlled trial evaluating the effects of Epoetin alfa on HRQOL in anemic hemodialysis patients. A total of 118 patients who were 18–75 years old, on hemodialysis for >3 months, who had a hemoglobin <9.0 g/dL, and did not have coronary artery disease or diabetes mellitus, were randomized to either receive placebo (n=40), or receive intravenous Epoetin alfa to achieve a target hemoglobin of 9.5–11.0 g/dL (n=40) or a target of 11.5–13.0 g/dL (n=38). Patients were followed for 6 months. The two Epoetin alfa‐treatment groups were combined for all analyses performed. This post hoc analysis was conducted using an intent‐to‐treat repeated measures mixed model analysis of variance using Bonferroni's multiplicity correction. The Epoetin alfa‐treated group showed a statistically significant improvement in the Kidney Disease Questionnaire symptom of fatigue in comparison with placebo. Additionally, the change in hemoglobin at 2 months was correlated with change in fatigue, energy, shortness of breath, and weakness, but had minimal effect on depression. These analyses confirm previously reported results, which indicate that treating hemodialysis patients with an erythropoiesis‐stimulating agent improves HRQOL.     

Reaching Target Hemoglobin after Hospitalization for Incident Hemodialysis Patients

Introduction:  The Kidney Disease Outcomes Quality Initiative (K/DOQI) has established target hemoglobin (Hb) level of 11–12 g/dL for all dialysis patients. For patients who leave an inpatient hospitalization with an Hb under this target, it is hypothesized that several factors contribute to the length of time required to achieve an Hb of 11 g/dL after hospitalization.
Objective:  To identify factors contributing to a decreased likelihood of reaching this target Hb.
Methods:  Using the first hospitalization of patients who initiated HD in 1999 and who were regularly treated with EPO, we identified those with a mean Hb of less than 11 g/dL on EPO claims during the same month as their index hospitalization. Patients were then followed up to see how long it took them to achieve an Hb of 11 g/dL, censored at death, re-hospitalization, a switch of modality, or suspension of EPO treatment.
Results:  A total of 6050 HD patients were identified. 3 months after hospitalization, 70% had achieved 11 g/dL, and 12% had been censored. For the remaining patients who eventually reached 11 g/dL, the average number of additional months required was 2.69 (SE of 0.09). From proportional hazards regression on the time (in months) to achieving an Hb of 11 g/dL, factors that significantly decreased the likelihood of reaching a target Hb included: a diagnosis on the index hospitalization of CHF or hepatic disease, a low Hb prior to the hospitalization, a high dose of EPO prior to the hospitalization, and a longer hospital stay.
Conclusions:  Patients with anemia after hospitalization are at high risk of both persistent anemia and rehospitalization. It is important to address patient comorbidities, to ensure adequate medication usage, and to monitor patient progress to prevent hospitalizations and potential impact on Hb levels.     

Effect of dialysis dose and membrane flux on hemoglobin cycling in hemodialysis patients

Many studies found that hemoglobin (Hb) fluctuation was closely related to the prognosis of the maintenance hemodialysis patients. We investigated the association of factors relating dialysis dose and dialyzer membrane with Hb levels. We undertook a randomized clinical trial in 140 patients undergoing thrice‐weekly dialysis and assigned patients randomly to a standard or high dose of dialysis; Hb level was measured every month for 12 months. In the standard‐dose group, the mean (±SD) urea reduction ratio was 65.1% ± 7.3%, the single‐pool Kt/V was 1.26 ± 0.11, and the equilibrated Kt/V was 1.05 ± 0.09; in the high‐dose group, the values were 73.5% ± 8.7%, 1.68 ± 0.15, and 1.47 ± 0.11, respectively. The standard deviation (SD) and residual SD (liner regression of Hb) values of Hb were significantly higher in the standard‐dose group and low‐flux group. The percentage achievement of target Hb in the high‐dose dialysis group and high‐flux dialyzer group was significantly higher than the standard‐dose group and low‐flux group, respectively. Patients undergoing hemodialysis thrice weekly appear to have benefit from a higher dialysis dose than that recommended by current KDQQI (Kidney Disease Qutcome Quality Initiative) guidelines or from the use of a high‐flux membrane, which is in favor of maintaining stable Hb levels.     

Physical function was related to mortality in patients with chronic kidney disease and dialysis

Previous studies have shown that exercise improves aerobic capacity, muscular functioning, cardiovascular function, walking capacity, and health‐related quality of life (QOL) in patients with chronic kidney disease (CKD) and dialysis. Recently, additional studies have shown that higher physical activity contributes to survival and decreased mortality as well as physical function and QOL in patients with CKD and dialysis. Herein, we review the evidence that physical function and physical activity play an important role in mortality for patients with CKD and dialysis. During November 2016, Medline and Web of Science databases were searched for published English medical reports (without a time limit) using the terms “CKD” or “dialysis” and “mortality” in conjunction with “exercise capacity,” “muscle strength,” “activities of daily living (ADL),” “physical activity,” and “exercise.” Numerous studies suggest that higher exercise capacity, muscle strength, ADL, and physical activity contribute to lower mortality in patients with CKD and dialysis. Physical function is associated with mortality in patients with CKD and dialysis. Increasing physical function may decrease the mortality rate of patients with CKD and dialysis. Physicians and medical staff should recognize the importance of physical function in CKD and dialysis. In addition, exercise is associated with reduced mortality among patients with CKD and dialysis.     

Orally administrated Juzen-taiho-to/TJ-48 ameliorates erythropoietin (rHuEPO)-resistant anemia in patients on hemodialysis

Maintenance of the red blood cell volume is a fundamental aspect of ensuring oxygen supply to the tissue. Recombinant human erythropoietin (rHuEPO) was approved for marketing in Japan in 1990 for the treatment of anemia in patients on dialysis. Recombinant human erythropoietin caused a significant increase in hemoglobin (Hb) levels in patients on dialysis. However, not all have a good response to rHuEPO therapy; the causes of rHuEPO failure include iron deficiency, infection, uremia, and interaction of some drugs. Juzen-taiho-to (TJ-48), a mixture of extracts from 10 medicinal herbs, has been used traditionally to treat patients with anemia, anorexia, or fatigue. To clarify the effect of TJ-48 on erythropoietin-resistant anemia, we studied the effect of TJ-48 in patients on hemodialysis with erythropoietin-resistant anemia. We divided 42 end-stage renal disease patients on hemodialysis with erythropoietin-resistant anemia (Hb<10.0 g/dL with rHuEPO 9000 U/wk or 15 U/kg/wk treatment) into 2 groups as follows: a TJ-48-treated group (TJ-48 group, 7.5 g/d, n=22) and a TJ-48 nontreated (control group, n=20). At the beginning of this study, there was no significant difference between the groups in age, sex, serum creatinine, blood urea nitrogen, serum iron, and ferritin. After 12 weeks of treatment, the Hb level had significantly increased from 8.4 +/- 1.1 to 9.5 +/- 1.3 g/dL (P=0.0272) in the TJ-48 group. C-reactive protein (CRP) had significantly decreased from 1.4 +/- 1.7 to 0.6 +/- 0.8 mg/dL (P=0.0438). There was a significant negative correlation between Hb and CRP in the TJ-48 group (r(2)=0.121, P=0.0066). In contrast, in the control group, Hb and CRP showed no significant changes throughout this study. Nor was there a significant correlation between Hb and CRP in the control group. In conclusion, TJ-48 was effective in improving erythropoietin-resistant anemia in end-stage renal disease patients. This effect was, at least in part, due to the anti-inflammatory effect of TJ-48 in patients on hemodialysis.     

Effects of silymarin on biochemical and oxidative stress markers in end‐stage renal disease patients undergoing peritoneal dialysis

Introduction End‐stage renal disease (ESRD) patients especially those undergoing dialysis are vulnerable to several complications, in particular those related to oxidative stress. Silymarin is an herbal medicine commonly used as an antioxidant in different pathologies. Methods To evaluate the effect of silymarin on biochemical and oxidative stress markers, 50 ESRD patients undergoing peritoneal dialysis were randomly divided into two groups of silymarin (n = 28) and control (n = 22) and received silymarin (140 mg every 8 hours) or placebo for 2 months, respectively. Ferric reducing antioxidant power and total 8‐iso‐prostaglandin F_2α were measured in plasma, while catalase enzyme activity was measured in erythrocytes of both groups before and after treatment. Findings Ferric reducing antioxidant power values after treatment were significantly decreased in silymarin group compared to before treatment values (17.2 ± 2.9 and 15.9 ± 3.1 µM equivalent of quercetin/dL, respectively, P < 0.05). Conversely, catalase levels were increased 17.3% after silymarin consumption, while it was decreased 9.1% in control group. Further, hemoglobin (from 10.94 ± 2.17 to 11.54 ± 2.03 g/dL, P < 0.05) and albumin levels (from 3.48 ± 0.67 to 3.61 ± 0.53 g/dL, P < 0.05) were significantly increased after silymarin administration. Discussion It is concluded that silymarin could be regarded as a supplementary therapy for ESRD patients undergoing peritoneal dialysis in order to reduce complications.     

Tailoring dialysis and resuming low‐protein diets may favor chronic dialysis discontinuation: Report on three cases

Renal function recovery (RFR), defined as the discontinuation of dialysis after 3 months of replacement therapy, is reported in about 1% of chronic dialysis patients. The role of personalized, intensive dialysis schedules and of resuming low‐protein diets has not been studied to date. This report describes three patients with RFR who were recently treated at a new dialysis unit set up to offer intensive hemodialysis. All three patients were females, aged 73, 75, and 78 years. Kidney disease included vascular‐cholesterol emboli, diabetic nephropathy and vascular and dysmetabolic disease. At time of RFR, the patients had been dialysis‐dependent from 3 months to 1 year. Dialysis was started with different schedules and was progressively discontinued with a “decremental” policy, progressively decreasing number and duration of the sessions. A moderately restricted low‐protein diet (proteins 0.6 g/kg/day) was started immediately after dialysis discontinuation. The most recent update showed that two patients are well off dialysis for 5 and 6 months; the diabetic patient died (sudden death) 3 months after dialysis discontinuation. Within the limits of small numbers, our case series may suggest a role for personalized dialysis treatments and for including low‐protein diets in the therapy, in enhancing long‐term RFR in elderly dialysis patients.     

A phase 3b,multicenter, open-label,single-arm study of roxadustat (ASPEN): Operational learnings within United States dialysis organizations

Introduction

Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved in several regions for the treatment of anemia of chronic kidney disease (CKD). ASPEN evaluated the efficacy, safety, and feasibility of roxadustat in patients with anemia of CKD in US dialysis organizations.

Methods

This open-label, single-arm study (NCT04484857) comprised a 6-week screening period, followed by 24 weeks of treatment (with optional extension ≤1 year) and a 4-week follow-up. Patients aged ≥18 years, receiving chronic dialysis, with hemoglobin (Hb) 9.0–12.0 g/dL if converting from erythropoiesis-stimulating agents (ESAs), or <10.0 g/dL if receiving ESAs for <6 weeks, received oral roxadustat three times weekly in-center. Primary efficacy endpoints included proportion of patients with mean Hb ≥10 g/dL, averaged over weeks 16–24, and mean Hb change from baseline to the average over weeks 16–24. Safety was also assessed.

Findings

Overall, 283 patients were enrolled and treated, 282 (99.6%) were included in the full analysis set, and 216 (76.3%) continued into the extension period. Most patients enrolled were from DaVita sites (71%), with the rest from US Renal Care sites (29%). Mean (standard deviation [SD]) baseline Hb was 10.6 (0.7) g/dL. Nearly all patients were prior ESA users (n = 274; 97.2%). The proportion of patients with mean Hb ≥10 g/dL during weeks 16–24 was 83.7% (95% confidence interval 78.9–88.6). Mean (SD) Hb increase from baseline to the average over weeks 16–24 was 0.2 (1.0) g/dL. During the treatment period, 82 (29.0%) patients reported treatment-emergent serious adverse events (TESAEs). The most common TESAEs were COVID-19 pneumonia (n = 10; 3.5%), acute respiratory failure (n = 9; 3.2%), COVID-19 (n = 7; 2.5%), acute myocardial infarction (n = 7; 2.5%), and fluid overload (n = 6, 2.1%).

Discussion

Roxadustat was effective in maintaining Hb in patients with anemia of CKD on dialysis in large, community-based dialysis organizations.     

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

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

Left ventricular mass index and aortic arch calcification score are independent mortality predictors of maintenance hemodialysis patients

To analyze predictive factors for all‐cause mortality, cardiovascular (CV) mortality, nonfatal CV events (CVE) in maintenance hemodialysis (MHD) patients, and to compare the effects of standard hemodialysis (HD) and online hemodiafiltration (HDF) on these factors and outcomes. A total of 333 MHD patients were prospectively followed up for 50 ± 15 months and all‐cause death, CV death and CVE were registered. At the baseline, demographic, clinical, and laboratory data of the whole population were recorded. Then, patients were stratified into two groups according to the dialysis modalities, HD (n = 268) and HDF (n = 65). At the end of 6th month, clinical and laboratory data were recorded again. The predictive factors at baseline for all‐cause mortality, CV mortality, and CVE were analyzed by Cox regression. The effects of HD and HDF on these factors at the 6th month and long‐term outcomes were compared by t‐test and Kaplan–Meier method, respectively. Age, gender, left ventricular mass index (LVMI), aortic arch calcification score (AoACS), hemoglobin (Hb) <10 g/dL, and ferritin >500 ng/mL maintained independent associations with all‐cause mortality. C‐reactive protein (CRP), LVMI, AoACS, and Hb <10 g/dL were associated with CV mortality. Prior cardiovascular disease (CVD), AoACS and LVMI were independent predictors of nonfatal CVE. Higher body mass index (BMI), body weight, total serum cholesterol, Hb concentration, and lower CRP level, LVMI, and AoACS were found in patients on HDF at the end of the 6th month. Improved outcomes with longer survival time for all‐cause mortality, CV mortality, and CVE were found in HDF group. Age, gender, LVMI, AoACS, Hb, and ferritin were predictors of all‐cause mortality in MHD patients. CRP, LVMI, AoACS, and Hb were associated with CV mortality. Prior CVD, AoACS, and LVMI were independent predictors of nonfatal CVE. HDF could improve BMI, body weight, total serum cholesterol, Hb, CRP, LVMI, AoACS, and long‐term outcomes, including all‐cause mortality, CV mortality, and CVE.     

Physical activity and self‐reported symptoms of insomnia,restless legs syndrome,and depression: The comprehensive dialysis study

Symptoms of sleep and mood disturbances are common among patients on dialysis and are associated with significant decrements in survival and health‐related quality of life. We used data from the Comprehensive Dialysis Study (CDS) to examine the association of self‐reported physical activity with self‐reported symptoms of insomnia, restless legs syndrome (RLS), and depression in patients new to dialysis. The CDS collected data on physical activity, functional status, and health‐related quality of life from 1678 patients on either peritoneal (n = 169) or hemodialysis (n = 1509). The Human Activity Profile was used to measure self‐reported physical activity. Symptoms were elicited in the following manner: insomnia using three questions designed to capture difficulty in initiating or maintaining sleep, RLS using three questions based on the National Institutes of Health workshop, and depression using the two‐item Patient Health Questionnaire. We obtained data on symptoms of insomnia and depression for 1636, and on symptoms of RLS for 1622 (>98%) patients. Of these, 863 (53%) reported one of three insomnia symptoms as occurring at a persistent frequency. Symptoms of RLS and depression occurred in 477 (29%) and 451 (28%) of patients, respectively. The Adjusted Activity Score of the Human Activity Profile was inversely correlated with all three conditions in models adjusting for demographics, comorbid conditions, and laboratory variables. Sleep and mood disturbances were commonly reported in our large, diverse cohort of patients new to dialysis. Patients who reported lower levels of physical activity were more likely to report symptoms of insomnia, RLS, and depression.     

C.E.R.A. once every 4 weeks in patients with chronic kidney disease not on dialysis: The ARCTOS extension study

C.E.R.A., a continuous erythropoietin receptor activator is approved for the treatment of anemia in patients with chronic kidney disease (CKD). The ARCTOS (administration of C.E.R.A. in CKD patients to treat anemia with a twice‐monthly schedule) phase 3 study demonstrated the efficacy and safety of C.E.R.A. in correcting anemia when administered once every 2 weeks (Q2W) subcutaneously in patients with CKD not on dialysis. We assessed the feasibility and long‐term safety of converting patients who responded to treatment with C.E.R.A. Q2W to C.E.R.A. once every 4 weeks (Q4W) during a 24‐week extension period. After the core ARCTOS study period (28 weeks), 296 patients entered the 24‐week extension period. At week 29, patients who responded to C.E.R.A. Q2W during the core period were rerandomized to receive subcutaneous C.E.R.A. Q2W or Q4W. Patients in the comparator arm could receive darbepoetin alfa once weekly or Q2W. Dosage was adjusted to maintain hemoglobin (Hb) between 11 and 13 g/dL. Mean Hb levels remained stable in all groups, and were comparable at the end of the extension period (mean [standard deviation], C.E.R.A. Q2W, 11.92 [0.90] g/dL; C.E.R.A. Q4W, 11.70 [0.86] g/dL; darbepoetin alfa, 11.89 [0.98] g/dL). Mean within‐patient standard deviation values for Hb were also comparable in all groups (0.66, 0.62, and 0.65 g/dL for C.E.R.A. Q2W, C.E.R.A. Q4W and darbepoetin alfa, respectively). All treatments were well tolerated. Subcutaneous C.E.R.A. Q4W is safe and effective in maintaining stable Hb levels in patients with CKD not on dialysis following correction with subcutaneous C.E.R.A. Q2W.     

Effects of modality change on health-related quality of life

Patients with end‐stage renal disease (ESRD) requiring renal replacement have impaired health‐related quality of life (HRQoL), and there is general consensus that HRQoL improves with successful transplant and evidence of improvement with frequent hemodialysis. This study reports changes in HRQoL associated with changes in treatment modality to daily hemodialysis (DHD) and transplant among patients requiring renal replacement. This cohort study had assessments at baseline and 6‐month following modality change. Subjects were nondiabetic individuals receiving conventional hemodialysis who (a) remained on conventional hemodialysis (n = 13), (b) changed to daily hemodialysis (DHD) (n = 10), or (c) received a living donor transplant (n = 20). Thirty‐four healthy controls were assessed once for comparison. HRQoL was measured using the Kidney Disease Quality of Life Instrument. The Physical Functioning and Physical Composite Scale scores were primary outcomes. Transplantation resulted in significant improvements in six of eight generic scales and the physical composite scale (PCS). Those changing to DHD had significant improvements in Physical Function and PCS scales. Those remaining on dialysis remained lower than controls on all scales except for Vitality; the transplant group remained lower than controls only on the Vitality and General Health scales. Transplant resulted in significant improvements in four of the seven disease‐specific scales (symptoms, effects, and burden of kidney disease, work). DHD resulted in improvements in the effects of kidney disease. Modality change to transplant results in significant improvement in HRQoL, achieving levels similar to controls. Change to daily hemodialysis improves only select HRQoL domains and remains low in disease‐specific domains.     

Effect of alternate night nocturnal home hemodialysis on anemia control in patients with end‐stage renal disease

Nocturnal home hemodialysis (NHHD) has shown promising results in various clinical parameters. Whether NHHD provide benefit in anemia management remains controversial. This study aims to investigate whether anemia and erythropoiesis‐stimulating agent (ESA) requirement are improved in patients receiving alternate night NHHD compared with conventional hemodialysis (CHD). In this retrospective controlled study, a clinical data of 23 patients receiving NHHD were compared with 25 in‐center CHD patients. Hemoglobin level, ESA requirement, iron profile, and dialysis adequacy indexes were compared between the two groups. Hemoglobin level increased from baseline of 9.37 ± 1.39 g/dL to 11.34 ± 2.41 g/dL at 24 months (P < 0.001) and ESA requirement decreased from 103.44 ± 53.55 U/kg/week to 47.33 ± 50.62 U/kg/week (P < 0.001) in NHHD patients. ESA requirement further reduced after the first year of NHHD (P = 0.037). Standard Kt/V increased from baseline of 2.02 ± 0.28 to 3.52 ± 0.30 at 24 months (P < 0.001). At 24 months, hemoglobin level increased by 1.98 ± 2.74 g/dL in the NHHD group while it decreased by 0.20 ± 2.32 g/dL in the CHD group (P = 0.007). ESA requirement decreased by 53.49 ± 55.50 U/kg/week in NHHD patients whereas it increased by 16.22 ± 50.01 U/kg/week in CHD patients (P < 0.001). Twenty‐six percent of NHHD patients were able to stop ESA compared with none in the CHD group. Standard Kt/V showed greater increase in the NHHD group. (1.49 ± 0.36 in NHHD vs. 0.18 ± 0.31 in CHD, P = 0.005). NHHD with an alternate night schedule improves anemia and reduces ESA requirement as a result of enhanced uremic clearance. This benefit extended beyond the first year of NHHD.     

The effect of intradialytic exercise twice a week on the physical capacity,inflammation, and nutritional status of dialysis patients: A randomized controlled trial

Introduction: Inactivity, uremia, and malnutrition in dialysis patients may lead to decreased muscle mass and physical capacity. As a preventative measure, dialysis patients are provided with an intradialytic exercise program. Our study aimed to determine the role of intradialytic exercise performed 2 times per week on physical capacity, inflammation, and nutritional status in dialysis patients and to determine which exercises are more suitable for this population. Methods: A randomized clinical trial in which participants were randomly assigned to 1 of 3 groups, i.e., a group of patients performing aerobic exercise, a group of patients performing a combination of aerobic and resistance exercise and the control group. The study was conducted at the Dialysis Unit of Dr. Cipto Mangunkusumo General Hospital, Jakarta for 12 weeks from February to May 2018. The inclusion criteria were dialysis patients aged over 18 years who had undergone routine dialysis for over 3 months. Findings: A total of one hundred twenty patients were included in the study. There was a significant increase in lower extremity strength in the group performing aerobic exercise and in the combined exercise group compared to the lower extremity strength of the control group. There was also a significant increase in the physical component score (PCS) of the KDQOL‐SF? instrument in the aerobic training and combination exercise groups compared to the PCS of the control group. No significant differences were found between the combination exercise group and the aerobic training group in any outcome. Discussion: Both types of exercise programs significantly increased the lower extremity muscle strength and the PCS of the quality of life index. Combination exercise was not more effective than aerobic exercise for dialysis patients.     

TSAT is a better predictor than ferritin of hemoglobin response to Epoetin alfa in US dialysis patients

Clinical guidelines recommend concurrent treatment of anemia in end‐stage renal disease with erythropoiesis‐stimulating agents (ESAs) and iron. However, there are mixed data about optimal iron supplementation. To help address this gap, the relationship between iron markers and hemoglobin (Hb) response to ESA (Epoetin alfa) dose was examined. Electronic medical records of 1902 US chronic hemodialysis patients were analyzed over a 12‐month period between June 2009 and June 2010. The analysis included patients who had at least one Hb value during each 4‐week interval for four consecutive intervals (k ? 2, k ? 1, k, and k + 1; k is the index interval), received at least one ESA dose during intervals k ? 1 or k, had at least one transferrin saturation (TSAT) value at interval k, and at least one ferritin value during intervals k ? 2, k ? 1, or k. Effect modification by TSAT and ferritin on Hb response was evaluated using the generalized estimating equations approach. Patients had a mean (standard deviation) age of 62 (15) years; 41% were Caucasian, 34% African American, 65% had hypertension, and 39% diabetes. Transferrin saturation, but not ferritin, had a statistically significant (P < 0.05) modifying effect on Hb response. Maximum Hb response was achieved when TSAT was 34%, with minimal incremental effect beyond these levels. Of the two standard clinical iron markers, TSAT should be used as the primary marker of the modifying effect of iron on Hb response to ESA. Long‐term safety of iron use to improve Hb response to ESA warrants further study.     

The level of C‐reactive protein in chronic hemodialysis patients: A comparative study between patients with noninfected catheters and arteriovenous fistula in two large Gulf hemodialysis centers

Hemodialysis (HD) patients have greater morbidity and mortality when they have a central venous catheter (CVC) rather than an arteriovenous fistula (AVF) access. Inflammation associated with dialysis catheter use and resultant higher C‐reactive protein (CRP) levels could have an independent adverse effect on patient outcomes. In this prospective study, we investigated whether HD catheters induce inflammation independent of infection. We compared the mean levels of the inflammatory marker (CRP) in 67 patients on maintenance HD using noninfected catheters with 86 HD patients using AVFs at Prince Salman Center for Kidney Diseases, Saudi Arabia (KSA), and Jahra Hospital, Kuwait, who met our inclusion criteria. C‐reactive protein levels were measured every 2 months over a period of 6 months using immunoturbidimetric assay. One hundred fifty‐three patients on maintenance HD for more than 6 months were included in the study, with mean age of 52.19 ± 16.06 years; 66% were males and 34% were females. Serial levels of mean CRP were statistically and significantly higher in group with noninfected catheters (1.33, 1.24, and 1.10 mg/dL) compared to those with AVFs (0.65, 0.59, and 0.68 mg/dL) with P value of 0.000. In our study, we found no relation between CRP level and age, sex, hemoglobin, albumin, calcium, phosphorus, and iPTH level in both groups. Hemodialysis patients with a catheter have a heightened state of inflammation independent of infection, and thus our study supports the avoidance of catheters and a timely conversion to AVFs with catheter removal.     

Ventricular arrhythmia in dialysis patients: A link with higher hemoglobin levels?

We investigated the frequencies and associated risk factors of cardiac arrhythmias and heart rate variability (HRV) in hemodialysis (HD) patients. One hundred fifty prevalent HD patients underwent 48-hour Holter monitoring. Holter monitoring was analyzed in 4 phases: early post-HD phase (12 hours), late post-HD phase (20 hours), pre-HD phase (12 hours), and HD phase (4 hours). Echocardiography was applied to measure the left ventricular mass index in a subgroup of patients (n: 52). Patients with ventricular premature contraction (VPC) were significantly older, had a longer HD duration, and higher hemoglobin (Hb) levels. Left ventricular mass index was significantly correlated with the frequency of VPC, during the HD and pre HD phases (r: 0.435, 0.312, respectively). In logistic regression analysis, patients with Hb level >11.9 g/dL (high tertile) had a 4.5-fold increased risk of VPC compared with those with Hb levels <10.8 g/dL (P: 0.04). In HRV analysis, age (P<0.001), and diabetes (P: 0.03) were found to be independent predictors of low standard deviation of all mean normal-to-normal RR intervals. Increased left ventricular mass index is associated with a high frequency of VPC in the pre-HD and HD periods. The occurrence of VPC is predicted by older age, longer dialysis duration, and higher Hb levels, while older age and diabetes are the determinants of HRV. The relation between higher Hb levels and the frequency of VPC might provide a clue for the explanation of the detrimental effect of higher Hb levels on HD patients.     

Nightly Home Hemodialysis: Fifteen Months of Experience in Lynchburg,Virginia

What constitutes adequate dialysis has been debated in the nephrology literature over the past eight years. The mortality rate of patients on dialysis in the United States is about 20% per year. We believed that short and infrequent dialysis sessions contributed to poor outcomes. To improve the results, Lynchburg Nephrology started the nightly home hemodialysis (NHHD) program in September 1997. Ten patients were trained in the first 15 months of the program. Patients dialyzed 7 – 9 hours, 6 nights/week, using the Fresenius 2008H machine. A standard dialysis solution with 2.0 mEq/L potassium, calcium concentration of 3.0 – 3.5 mEq/L was used. Dialysis solution flow rates were 200 – 300 mL/min. Serum phosphate levels were maintained above 2.5 mg/dL by adding 0 – 45 mL Fleet's Phosphosoda to the bicarbonate bath. Patients had marked improvement in quality of life as measured with the SF-36. Blood pressure was better controlled with fewer medications. All phosphate binders were eliminated. Caloric intake and protein intake increased to normal levels as measured by three-day dietary histories pre-NHHD, and at 3, 6, and 12 months on NHHD. Epoetin alfa dosages were reduced by about 50%. Nightly home hemodialysis should be considered as a valuable modality option for end-stage renal disease patients; it is potentially superior to conventional thrice-weekly hemodialysis.     

Physical functioning in end-stage renal disease patients: update 2005

Physical functioning in patients with end-stage renal disease treated with dialysis is low, whether measured using objective laboratory measures, physical performance testing, or self-reported measures. Peak oxygen uptake (VO2peak), self-reported functioning measures, and physical activity levels are independent predictors of mortality in these patients. Cardiovascular exercise training studies result in improvements in VO2peak, physical performance tests, and self-reported functioning. Resistance exercise training improves muscle strength. Exercise training may have positive benefits on other factors that are important clinical issues in dialysis patients, including cardiovascular risk profile, oxidative stress, and inflammation. Endothelial function, a surrogate marker of atherosclerosis, has been shown to improve with exercise training in dialysis patients. Although there have been numerous recent studies on benefits of exercise, few dialysis clinics or nephrologists provide encouragement or programs as a part of their routine care of their patients. There are many national guidelines that include exercise or increasing physical activity as a part of the treatment of many conditions that are relevant in dialysis patients, including hypertension, hyperlipidemia, and high cardiovascular disease risk. The nephrology community continues to state concern for outcomes; however, a simple, low-tech intervention that has many benefits to their patients (i.e., encouragement, recommendations, and opportunity for increasing physical activity) has not been adopted as part of the standard care. Adoption of routine counseling and encouragement for physical activity has the potential to improve outcomes, improve physical functioning, and optimize quality of life and overall health of dialysis patients.