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

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

Global ESRD Costs Associated with a Short Daily Hemodialysis Program in the United States

In spite of the growing evidence that daily hemodialysis (DHD) improves clinical outcomes and quality of life, the additional dialysis costs are not currently reimbursed in the United States. Nor have there been reports of the effects of DHD on end-stage renal disease (ESRD) global costs, which would help predict the financial impact of DHD on the ESRD program. Since 1996, 22 patients (20 in-center, 2 home) have switched from conventional thrice-weekly dialysis to short, daily dialysis with six treatments per week. Eighteen patients started for medical indications, and four started for nonmedical reasons. Causes of ESRD were the following: diabetes mellitus (6), hypertension (4), glomerulonephritis (6), hereditary (2), and other (4). Mean age was 56 ± 16 years. Patients had an average of 3.3 major comorbidities. Weekly conventional HD dialysis times were divided into six DHD treatments, each 2.0 ± 0.3 hours. Weekly Kt/V remained unchanged. Twenty-two patients were followed on DHD for 220 patient-months: 7 patients died after 1.8 ± 1.3 months, 2 were transplanted at 4.3 ± 3.2 months, and 2 discontinued DHD at 3.6 ± 4.8 months. Eleven patients remain on DHD at 17.4 ± 8.3 months. Actual costs per extra dialysis session are as follows: $14.30 for supplies and $3.20 for labor for setup/cleanup time (15 minutes at $12.80/hour). Annualized DHD savings are based on comparison of doses of epoetin alpha (Epogen) and blood pressure medication at the start and after 12 months of DHD. Hospitalization rates include all enrolled patients, comparing rates for the 12 months prior to DHD with the first year on DHD, or annualized rates for those on DHD less than one year. Cost assumptions are $9/ 1000 U Epogen, $1/blood pressure pill, and $1200/per day of hospitalization. Extra transportation costs were covered by the patients. No increased access problems were observed. For patients on short DHD longer than 12 months, supply and labor costs increased to $2733/patient/year; however, Epogen use was reduced 55%, and blood pressure medications were reduced 40%. For all patients who switched to DHD, hospitalization rates were reduced 24%. This resulted in a net savings of about $4241/patient/ year after 12 months on DHD. Overall ESRD costs were substantially decreased on DHD. These cost savings must be passed on to providers before DHD becomes more widely available.     

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.     

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.     

Challenges of providing maintenance hemodialysis in a resource poor country: Experience from a single teaching hospital in Lagos,Southwest Nigeria

Providing maintenance hemodialysis is associated with high costs and poor outcomes. In Nigeria, more than 90% of the population lives below the poverty line, and patients with end‐stage renal disease (ESRD) pay out‐of‐pocket for maintenance hemodialysis. To highlight the challenges of providing maintenance hemodialysis for patients with ESRD in Nigeria, we reviewed records of all patients who joined the maintenance hemodialysis program of our dialysis unit over a 21‐month period. Information regarding frequency of hemodialysis, types of vascular access for dialysis, mode of anemia treatment and frequency of blood transfusion received were retrieved. One hundred and twenty patients joined the maintenance hemodialysis program of our unit during the period under review. Seventy‐two (60%) were males and the mean age of the study population was 47 + 14 years. The mean hemoglobin concentration at commencement of dialysis was 7.3 g/dL + 1.6 g/dL. The initial vascular access was femoral vein cannulation in all the patients. A total of 73.5% of the patients required blood transfusion at some point with 33% receiving five or more pints of blood. Only 3.3% of the patients had thrice weekly dialysis, 21.7% dialyzed twice weekly, 23.3% once weekly, 16.7% once in two weeks, 2.5% once in three weeks and 11.7% once monthly. At the time of review, 8.3% of the patients had died while 38.3% were lost to follow‐up. Majority of patients with ESRD on maintenance hemodialysis in our unit were poorly prepared for dialysis, were under‐dialyzed, and were frequently transfused with blood with resultant poor outcomes.     

The Glycemic Indices in Dialysis Evaluation (GIDE) study: Comparative measures of glycemic control in diabetic dialysis patients

The validity of hemoglobin A1c (HgbA1c) is undergoing increasing scrutiny in the advanced CKD/ESRD (chronic kidney disease/end‐stage renal disease) population, where it appears to be discordant from other glycemic indices. In the Glycemic Indices in Dialysis Evaluation (GIDE) Study, we sought to assess correlation of HgbA1c with casual glucose, glycated albumin, and serum fructosamine in a large group of diabetic patients on dialysis. From 26 dialysis facilities in the United States, 1758 diabetic patients (hemodialysis = 1476, peritoneal dialysis = 282) were enrolled in the first quarter of 2013. The distributions of HgbA1c and the other glycemic indices were analyzed. Intra‐patient coefficients of variation and correlations among the four glycemic indices were determined. Patients with low HgbA1c values were both on higher erythropoietin (ESA) doses and more anemic. Serum glucose exhibited the highest intra‐patient variability over a 3‐month period; variability was modest among the other glycemic indices, and least with HgbA1c. Statistical analyses inclusive of all glycemic markers indicated modest to strong correlations. HgbA1c was more likely to be in the target range than glycated albumin or serum fructosamine, suggesting factors which may or may not be directly related to glycemic control, including anemia, ESA management, and iron administration, in interpreting HgbA1c values. These initial results from the GIDE Study clarify laboratory correlations among glycemic indices and add to concerns about reliance on HgbA1c in patients with diabetes and advanced kidney disease.     

The economics and practicality of t‐PA vs tunnel catheter replacement for hemodialysis

Introduction: Thrombolytic therapy is an important treatment modality for thrombosis‐related catheter occlusion. Central venous access devices (CAVDs) are essential tools for the administration of many therapeutic modalities, especially for patients requiring lifetime therapy like hemodialysis. There are several reasons to salvage the occluded catheter. Catheter replacement results in an interruption of therapy delivery. This interruption may result in complications such as life‐threatening metabolic and physiologic states. In addition, the patient's future access sites for CAVDs may be affected. The data released in the 2001 Annual Report – ESRD Clinical Performance Measures Project (Department of Health and Human Services, December 2001) shows 17% of prevalent patients were dialyzed with a chronic catheter continuously for 90 days or longer. In the pediatric population the data shows that 31% were dialyzed with a chronic catheter. The most common reasons for catheter placement included: no fistula or graft created (42%) and fistula and graft were maturing, not ready to cannulate (17%). Five percent of patients were not candidates for fistula or graft placement as all sites had been exhausted. Methods: A short study was done in our medical center to evaluate the results of t‐PA vs. changing the tunnel catheter. On an average a catheter costs about $400.00. If you add the cost of specialty personnel such as an interventional radiologist, radiology technician, radiology nurse, and the ancillaries such as the room, sutures, gauze, and tape, the total could reach $2000.00 easily. Cathflo? Activase® costs around $60.00 for a single dose. T‐PA was reconstituted by pharmacy personnel in single vials containing 2 mg/2 ml. Now with Cathflo, vials are stored in the renal clinic's refrigerator and when the need arises, the RN reconstitutes the medication. The RN, using established protocols, will instill Cathflo in the catheter following the volume requirements of the various tunnel catheters. After the t‐PA is placed, the patient is sent home with instructions to return to their dialysis center the next day (arrangements are made by the RN as needed). In seventeen patients (17) with tunnel catheter malfunctions due to inadequate flow, not related to placement, t‐PA was used. Of those 17 patients 2 were unable to use their catheter on their next dialysis treatment date, yielding an 88% success rate. This compares with clinical trials in which there is an 83% success rate with a dwell time of 4 hours, or an 89% rate on patients having a 2 hour dwell time (t‐PA was repeated a second time if flow was not successfully restored. Results: 15/17 patients in our retrospective study showed that Cathflo worked successfully in restoring blood flow. Two catheters needed to be exchanged. The cost savings were significant when we compared the average cost of an exchange ($2000) versus using t‐PA ($170 including nursing time). Conclusion: Cathflo is not just safe and practical to use but also cost effective.     

Pharmacologic adjuvants to epoetin in the treatment of anemia in patients on hemodialysis

Anemia is a common complication of chronic kidney disease, particularly in patients who are on dialysis. The use of recombinant human erythropoietin has led to the eradication of severe anemia in the dialysis population. Correction of anemia in these patients has been associated with better quality of life and clinical outcomes. Some hemodialysis patients have anemia that either is relatively refractory to epoetin therapy or requires very high doses of epoetin (i.e., hyporesponsiveness), despite having adequate iron stores, and are thus unable to achieve or maintain target hemoglobin levels. Several pharmacologic agents have been studied for effects on improving response to epoetin, either to counter hyporesponsiveness or simply to reduce epoetin use for purely economic reasons. This review examines the available literature regarding the efficacy of these potential pharmacologic adjuvants to epoetin in the treatment of anemia in patients on maintenance hemodialysis, with special emphasis on androgens, vitamin C (ascorbic acid), and L-carnitine. A review of published guidelines and recommendations for use of these agents in hemodialysis patients is provided.     

The marginal cost of satellite versus in-center hemodialysis

Background: Despite increasing numbers of patients receiving hemodialysis in satellite units (SHD), the economic aspects have not been widely explored. A cost analysis of SHD and in‐center hemodialysis (ICHD) from a societal perspective was performed to establish the efficiencies associated with shifting resources and patients from ICHD to SHD. Methods: Costs were classified as fixed or variable and placed into categories. The resources for operating a SHD unit are the sum of two components: total fixed costs (TFC) and average variable cost (AVC) times SHD patient volume (Q). Using the TFC of a specific‐sized SHD unit and the difference in AVC between ICHD and SHD the number of patients needed (Q) in the SHD unit for financial viability was determined. The formula TFC = (AVC_ICHD ? AVC_SHD) X Q was used to determine the number of patients (Q) needed in a specific‐sized SHD unit such that the yearly cost of SHD treatment would be the same as ICHD treatment. Results: Our results show that SHD fixed costs can be fully offset if the volume of SHD patients is seven per year in a six‐station unit. SHD costs were lower for nursing and physician fees. Therefore, ICHD care variable costs were $11,374 more per patient year. SHD patients would also have lower travel costs, a mean cost saving of $12,364 per year. Conclusion: SHD can result in significant savings both to the health‐care system and to patients. Using the cost categories and formula presented, the number of patients needed in a specific‐sized satellite unit to realize cost savings was determined for our program. We found that these savings can offset the fixed investment needed to operate a SHD unit at modest patient volumes.     

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.     

Exceeding hemoglobin target levels in US hemodialysis patients receiving epoetin, 1999 to 2002

Despite emerging concerns that exceeding anemia targets with erythropoiesis stimulating agents may be risky for hemodialysis patients, the magnitude of and risk factors for the problem have received little attention, particularly regarding year-to-year comparisons. We studied monthly hemoglobin and epoetin levels in 41,101 patients aged at least 65 years who initiated hemodialysis between 1999 and 2002, with upper targets defined by hemoglobin levels of 120 and 130 g/L, respectively. While baseline hemoglobin values and epoetin doses rose from year to year, their rates of change during follow-up declined (p<0.0001). Similar patterns were seen after reaching hemoglobin levels of 110 g/L; comparing 1999 to 2002, the proportions reaching 120 and 130 g/L in the ensuing 9 months increased from 90% to 96% (p<0.0001) and from 56% to 69%, respectively (p<0.0001). Multivariate analysis showed that, while more recent years of dialysis inception and initial epoetin dose were associated with all 3 outcomes, higher baseline hemoglobin levels were associated with reaching levels of 110 and 120 g/L, but not 130 g/L. Exceeding hemoglobin level targets has become widespread in the United States and is associated with changes in epoetin dosing practices.     

The greatly misunderstood erythropoietin resistance index and the case for a new responsiveness measure

Introduction The optimal use of erythropoiesis stimulating agents (ESAs) to treat anemia in end stage renal disease remains controversial due to reported associations with adverse events. In analyzing these associations, studies often utilize ESA resistance indices (ERIs), to characterize a patient's response to ESA. In this study, we examine whether ERI is an adequate measure of ESA resistance. Methods We used retrospective data from a nonconcurrent cohort study of incident hemodialysis patients in the United States (n = 9386). ERI is defined as average weekly erythropoietin (EPO) dose per kg body weight (wt) per average hemoglobin (Hgb), over a 3‐month period (ERI = (EPO/wt)/Hgb). Linear regression was used to demonstrate the relationship between ERI and weight‐adjusted EPO. The coefficient of variation was used to compare the variability of Hgb with that of weight‐adjusted EPO to explain this relationship. This analysis was done for each quarter during the first year of dialysis. Findings ERI is strongly linearly related with weight‐adjusted EPO dose in each of the four quarters by the equation ERI = 0.0899*(EPO/wt) (range of R² = 0.97–0.98) and weakly linearly related to 1/Hgb (range of R² = 0.06–0.16). These correlations hold independent of age, sex, hgb level, ERI level, and epo‐naïve stratifications. Discussion ERI is strongly linearly related to weight‐adjusted (and nonweight‐adjusted) EPO dose by a “universal,” not patient‐specific formula, and thus is a surrogate of EPO dose. Therefore, associations between ERI and clinical outcomes are associations between a confounded EPO dose and those outcomes.     

Naturally nonanemic dialysis patients: Who are they?

Introduction Not only anemia, but also erythropoiesis stimulating agent (ESA)s for treating anemia may adversely affect prognosis of chronic hemodialysis patients. Various features of naturally (with no ESA usage) nonanemic patients may be useful for defining several factors in the pathogenesis of anemia. Methods Data, retrieved from the European Clinical Database (EuCliD)‐Turkey on naturally nonanemic prevalent chronic hemodialysis patients (n: 201) were compared with their anemic (those who required ESA treatment) counterparts (n: 3948). Findings Mean hemoglobin values were 13.5 ± 0.8 and 11.5 ± 0.9 g/dL in nonanemic and anemic patients, respectively (P < 0.001). Nonanemia status was associated with younger age, male gender, longer dialysis vintage, nondiabetic status, more frequent hepatitis‐C virus seropositivity and more frequent arteriovenous fistula usage. Serum ferritin and CRP levels and urea reduction ratio were higher in ESA‐requiring patients. One (99%) and two (95.3%) years survival rates of the “naturally nonanemic” patients were superior as compared to anemics (91.0% and 82.6%, respectively), (P < 0.001). Discussion “Naturally nonanemic” status is associated with better survival in prevalent chronic hemodialysis patients; underlying mechanisms in this favorable outcome should be investigated by randomized controlled trials including large number of patients.     

Tinzaparin reduces health care resource use for anticoagulation in hemodialysis

Anticoagulation is required during hemodialysis to prevent thrombus formation within the extracorporeal circuit. The low-molecular-weight heparin tinzaparin is more expensive than unfractionated heparin (UFH) in Canada but more convenient to administer. We conducted a time-and-motion study to test the hypothesis that tinzaparin may reduce nursing time and total health care costs compared with UFH. Data on health care resource use associated with anticoagulation during hemodialysis for chronic renal failure were collected at an academic hospital in Quebec. Nursing time was recorded for 8 nurses performing 16 dialysis sessions for 4 patients receiving tinzaparin and 4 receiving UFH (2 dialysis sessions per patient). Nurses had ≥ 1 year of experience supervising hemodialysis. We estimated total annual costs of nursing time and health care resources (anticoagulants, medical supplies, and laboratory testing) associated with anticoagulation. In sensitivity analyses, drug costs were varied ± 30% of their base-case values. Estimated annual nursing times per patient were 0.8 vs. 11.5 hours in the first year and 0.6 vs. 10.2 hours in subsequent years for tinzaparin vs. UFH, respectively. Annual drug costs per patient were CAD 898.56 for tinzaparin and 546.75 for UFH. Estimated total annual costs were CAD 1061.03 vs. 1012.71 in the first year and CAD 917.75 vs. 895.23 in subsequent years for tinzaparin vs. UFH, respectively. Use of tinzaparin was cost saving relative to UFH if tinzaparin price was reduced 30%. Most of the price differential between tinzaparin and UFH is offset by substantial time savings to nephrology nurses.     

Left ventricular geometric patterns in end‐stage kidney disease: Determinants and course over time

Introduction : While concentric left ventricular hypertrophy (cLVH) predominates in non–dialysis‐dependent chronic kidney disease (CKD), eccentric left ventricular hypertrophy (eLVH) is most prevalent in dialysis‐dependent CKD stage 5 (CKD5D). In these patients, the risk of sudden death is 5× higher than in individuals with cLVH. Currently, it is unknown which factors determine left ventricular (LV) geometry and how it changes over time in CKD5D. Methods : Data from participants of the CONvective TRAnsport Study who underwent serial transthoracic echocardiography were used. Based on left ventricular mass (LVM) and relative wall thickness (RWT), 4 types of left ventricular geometry were distinguished: normal, concentric remodeling, eLVH, and cLVH. Determinants of eLVH were assessed with logistic regression. Left ventricular geometry of patients who died and survived were compared. Long‐term changes in RWT and LVM were evaluated with a linear mixed model. Findings : Three hundred twenty‐two patients (63.1 ± 13.3 years) were included. At baseline, LVH was present in 71% (cLVH: 27%; eLVH: 44%). Prior cardiovascular disease (CVD) was positively associated with eLVH and ß‐blocker use inversely. None of the putative volume parameters showed any relationship with eLVH. Although eLVH was most prevalent in non‐survivors, the distribution of left ventricular geometry did not vary over time. Discussion : The finding that previous CVD was positively associated with eLVH may result from the permanent high cardiac output and the strong tendency for aortic valve calcification in this group of long‐term hemodialysis patients, who suffer generally also from chronic anemia and various other metabolic derangements. No association was found between eLVH and parameters of fluid balance. The distribution of left ventricular geometry did not alter over time. The assumption that LV geometry worsens over time in susceptible individuals, who then suffer from a high risk of dying, may explain these findings.     

Effect of vitamin D supplementation on endothelial dysfunction in hemodialysis patients

Introduction: Patients with chronic kidney disease (CKD) commonly experience 25‐hydroxyvitamin D3 (25‐OH‐D3) deficiency, and these patients have a higher incidence of cardiovascular diseases (CVDs) due to endothelial dysfunction (ED). The aim of our study was to investigate the effect of 25‐OH‐D3 deficiency and its supplementation on ED in patients with CKD. Methods: Twenty‐nine uremic patients on dialysis and 20 healthy controls were evaluated for ED by high‐resolution Doppler ultrasonography of the brachial artery. In addition, 25‐OH‐D3‐deficient patients (25‐OH‐D3 < 30 nmol/L) with CKD and healthy controls were evaluated for ED before and after 8 weeks of oral vitamin D (cholecalciferol, 50,000 units) treatment. All subjects were evaluated for percent flow‐mediated dilatation (%FMD), percent endothelium‐independent nitroglycerin‐induced vasodilatation (%NID), and bilateral carotid intima‐media thickness (CIMT). Findings: Patients on dialysis had lower %FMD and %NID 6.11 [2.27–12.74] and 10.96 [5.43–16.4], respectively, than controls 15.84 [8.19–22.49] and 21.74 [12.49–29.4], respectively (P < 0.05). Patients on dialysis had higher left and right CIMT (0.79 ± 0.15 and 0.78 ± 0.14, respectively) than controls (0.60 ± 0.09 and 0.59 ± 0.09, respectively; P < 0.05). In 25‐OH‐D3‐deficient patients with CKD, after vitamin D treatment, %FMD was significantly increased in dialysis patients (10.25 [7.8–12.8]) compared to before supplementation (5.4 [2.77–6.15]; P < 0.001). Discussion: These results indicated that dialysis patients had significantly lower blood 25‐OH‐D3 levels and higher CIMT than healthy subjects. In addition, vitamin D supplementation improved ED and increased %FMD in dialysis patients. Our findings suggest that vitamin D supplementation in dialysis patients might prevent CVD.     

Collection of daily patient reported outcomes is feasible and demonstrates differential patient experience in chronic kidney disease

Introduction: Patient reported outcomes (PROs) are a critical metric documenting the impact of disease and treatment from the patient's perspective. A variety of generic and disease specific PRO measures (PROMs) are used in chronic kidney disease (CKD) but studies are primarily cross‐sectional. None of the available PROMs are designed for frequent iterative application. Methods: An online PROM for daily use in dialysis and CKD 4/5 patients was developed. The custom website utilised visual analogue scales to capture 6 PROs (general well being (GWB), pain, sleep, breathing, energy, and appetite). Outcomes of interest were uptake, response rates, intermodality variation, and change in PRO corresponding to predefined events. Findings: Forty‐three patients submitted at least once and 34 submitted beyond 30 days. Median follow‐up was 247 days, 64% male, age 62 ± 12 years. In individuals submitting for >30 days, dialysis patients had significantly worse median scores compared to CKD for sleep (47[32–80], 97[76–99], P = 0.003), appetite (66[50–96], 97[88–100], P = 0.008), energy (47[40–89], 84[67–96], P = 0.031), and GWB (63[49–94], 93[71–98], P = 0.026). Patients demonstrated a variety of stable bandwidths of response, deviations from this were associated with specific events e.g., acute admission, vascular procedures, disturbed fluid status, and dialysis start. Discussion: We successfully introduced an online, patient acceptable, iterative PROM that discriminates symptom burden, cross‐sectionally, and longitudinally. Further work will prospectively examine the predictive power of changes in PRO and more rigorously investigate the potential use of these methods to optimise patient care.     

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.