Perihospitalization hemoglobin-epoetin associations in U.S. hemodialysis patients, 1998 to 2003

While hospitalization is common for hemodialysis patients, perihospitalization associations between hemoglobin levels and epoetin doses are not well characterized. U.S. Medicare claims were used to identify 71,360 hemodialysis patients hospitalized from 1998 to 2003. Hemoglobin levels, epoetin doses, and epoetin responsiveness index (ERI) were compared by calendar year. In the prehospitalization month, the mean hemoglobin levels increased from 10.96 g/dL in 1998 to 11.76 in 2003 and the mean epoetin doses from 63,715 to 75,012 U; corresponding values in the hospitalization month were 10.53 and 11.19 g/dL, and 66,623 and 80,569 U. In each year, prehospitalization hemoglobin levels were achieved within 2 months, but ERI declined to prehospitalization levels within 12 months only in 2000. With mixed models, hemoglobin declines in the 3 prehospitalization months grew between 1998 (-0.1362 g/dL/month) and 2003 (-0.2003 g/dL/month). Epoetin responsiveness index slopes were J-shaped, with values of 287.9, 221.1, and 356.5U/month per g/dL in 1998, 2000, and 2003. In the 3 postadmission months, a modest increase in the rapidity of hemoglobin recovery was seen (+0.2538 g/dL/month in 1998, +0.2743 in 2003), with increasing rates of ERI change (+8.7 U/month/g/dL in 1998, +146.8 in 2003). While time to recovery of prehospitalization hemoglobin levels remained constant year to year, epoetin doses and ERI did not, suggesting that optimum perihospitalization anemia management practices have yet to be determined.     

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.     

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.     

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.     

Effect of ethnicity on erythropoietin therapy response for hemodialysis patients: A retrospective study

Anemia is a common feature in chronic kidney disease patients due to deficiency of erythropoietin (EPO). Diseased kidneys are unable to produce EPO, which enhances red blood cell production from the bone marrow. Recombinant human EPO in hemodialysis patients was introduced with perfect outcomes as a hormonal substitutive treatment. Some ethnic minority groups have high prevalence of anemia associated with chronic kidney diseases. The aim of this study is to evaluate the differences between African Caribbeans and Caucasians’ EPO therapy response with regard to hemoglobin (Hb), some factors affecting it and some comorbid conditions. A retrospective study for 6 months of 100 patients on hemodialysis was conducted on two ethnic minorities groups; 46 patients were African Caribbean and 54 patients were Caucasian, who received EPO therapy at once or three times weekly dose at the Hanbury Dialysis Unit of Royal London Hospital. There were three types of EPO therapy used: Aranesp, Mircera and Neorecormon. Forty‐six patients were African Caribbean and 54 patients were Caucasian. There were 63.4% of patients treated by Aranesp while 13% were given Mircera; 22.8% of the sample used Neorecorman. It was shown that the chosen comorbid conditions had higher percentage in the African Caribbeans than in Caucasians. Diabetic and/or hypertensive patients are almost double the patient numbers. In addition, sickle cell anemia is only present in African Caribbeans. There were 43.5% of African Caribbeans and 81.1% of Caucasians who met the standards of Hb level. There was no significant difference between African Caribbeans and Caucasians regarding parathyroid hormone, c‐reactive protein, B12, mean corpuscular volume, ferritin, and folate. In this study, there was a significant difference in the Hb levels between African Caribbean and Caucasian groups. Sixty percent of African Caribbeans had mean Hb less than normal levels. However, they received lower EPO dose than Caucasians. As a result, this may affect the whole treatment and therapy which may lead to anemic complications.     

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.     

HFE gene mutation is a risk factor for tissue iron accumulation in hemodialysis patients

Introduction: HFE gene mutations are responsible from iron overload in general population. Studies in hemodialysis patients investigated the effect of presence of HFE gene mutations on serum ferritin and transferrin saturation (TSAT) with conflicting results. However effect of HFE mutations on iron overload in hemodialysis patients was not previously extensively studied. Methods: 36 hemodialysis patients (age 51.3 ± 15.6, (18/18) male/female) and 44 healthy control subjects included in this cross sectional study. Hemoglobin, ferritin, TSAT in the preceding 2 years were recorded. Iron and erythropoietin (EPO) administered during this period were calculated. Iron accumulation in heart and liver was detected by MRI. Relationship between HFE gene mutation, hemoglobin, iron parameters and EPO doses, and tissue iron accumulation were determined. Findings: Iron overload was detected in nine (25%) patients. Hemoglobin, iron parameters, weekly EPO doses, and monthly iron doses of patients with and without iron overload were similar. There was no difference between control group and hemodialysis patients with respect to the prevalence of HFE gene mutations. Iron overload was detected in five of eight patients who had HFE gene mutations, but iron overload was present in 4 of 28 patients who had no mutations (P = 0.01). Hemoglobin, iron parameters, erythropoietin, and iron doses were similar in patients with and without gene mutations. HFE gene mutations remained the main determinant of iron overload after multivariate logistic regression analysis (P = 0.02; OR, 11.6). Discussion: Serum iron parameters were not adequate to detect iron overload and HFE gene mutation was found to be an important risk factor for iron accumulation.     

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.     

IL-6 is an independent risk factor for resistance to erythropoiesis-stimulating agents in hemodialysis patients without iron deficiency

Anemia is a common complication in dialysis patients because of their relative erythropoietin deficiency. Despite treatment with erythropoiesis-stimulating agents (ESAs), some patients experienced ESA hyporesponsiveness. We evaluated the clinical and laboratory factors that affect ESA hyporesponsiveness and investigated the relationships between hepcidin, inflammatory markers, and the iron profiles of hemodialysis patients. Sixty-eight patients receiving hemodialysis at a single institution were evaluated in a cross-sectional study. The patients were divided into tertiles based on the ESA hyporesponsiveness index (EHRI), defined as the weekly ESA dose per kilogram of body weight divided by the hemoglobin level. The mean EHRI values for each tertile were 3.3 ± 1.2 (T1), 10.2 ± 2.9 (T2), and 24.5 ± 11.6 (T3). The mean serum erythropoietin levels were significantly higher in the Q3 and Q4 groups. Thus, patients with ESA hyporesponsiveness showed relative resistance to erythropoietin therapy. In univariate and multivariate analyses, patients in the third tertile of EHRI showed significantly higher mean interleukin-6 (IL-6) levels. Serum C-reactive protein (CRP) levels showed a similar trend, but the differences were not significant. Serum hepcidin levels tended toward lower mean values in the third tertile of EHRI. No relationship was observed between hepcidin and inflammatory markers or iron status. In conclusion, IL-6, but not CRP, is a strong predictor of ESA hyporesponsiveness in hemodialysis patients who have sufficient iron. It may be difficult to use hepcidin as an independent clinical marker because of the many factors that influence it and their interactions.     

Plasma vitamin C levels in ESRD patients and occurrence of hypochromic erythrocytes

Introduction: The achievement of erythropoiesis in hemodialysis (HD) patients is typically managed with erythropoiesis‐stimulating‐agents (ESA's) and intravenous iron (IV‐iron). Using this treatment strategy, HD patients frequently show an elevated fraction of red blood cells (RBC) with hemoglobin (Hb) content per cell that is below the normal range, called hypochromic RBC. The low Hb content per RBC is the result of the clinical challenge of providing sufficient iron content to the bone marrow during erythropoiesis. Vitamin C supplements have been used to increase Hb levels in HD patients with refractory anemia, which supports the hypothesis that vitamin C mobilizes iron needed for Hb synthesis. Methods: We conducted a cross‐sectional survey in 149 prevalent HD patients of the percent hypochromic RBC, defined as RBC with Hb < 300 ng/uL of packed RBC, in relation to plasma vitamin C levels. We also measured high‐sensitivity CRP, (hs‐CRP), iron, and ferritin levels. and calculated ESA dose. Findings: High plasma levels of vitamin C were negatively associated with hypochromic RBC (P < 0.003), and high ESA doses were positively associated (P < 0.001). There was no significant association of hs‐CRP with percent hypochromic RBC. Discussion: This finding supports the hypothesis that vitamin C mobilizes iron stores, improves iron delivery to the bone marrow, and increase the fraction of RBC with normal Hb content. Further research is warranted on development of protocols for safe and effective use of supplemental vitamin C for management of renal anemia.     

Epidemiology of end‐stage renal disease and hemodialysis treatment in Serbia at the turn of the millennium

The study presents the epidemiological features of patients treated with renal replacement therapy (RRT) in Serbia from 1997 to 2009 and compares the results of hemodialysis treatment in 1999 and 2009. Epidemiological data were obtained from the National Registry of RRT patients and data on hemodialysis treatment from special surveys conducted in 1999 and 2009. Within the period 1997–2009 the incidence of patients on RRT increased from 108 to 179 per million population (pmp), prevalence rose from 435 to 699 pmp, while mortality rate fell from 20.7% to 16.7%. The frequency of patients with glomerulonephritis decreased, while that of patients with diabetes and hypertensive nephropathy increased. In late 2009 there were 5208 patients receiving RRT in Serbia. Within the examined period new hemodialysis and reverse osmosis equipment were purchased, high‐flux dialyzers with synthetic membranes were increasingly used and the number of patients receiving hemodiafiltration increased to 17.6%. Kt/V greater than 1.2 was recorded in 16% of the patients in 1999 but 52% in 2009. Options for correction of anemia and mineral disorders have also improved. The percentage of patients with HbsAg (13.8% vs. 4.8%) as well as anti‐hepatitis C virus antibodies positive patients (23.2% vs. 12.7%) was significantly lower in 2009 than in 1999. Both the incidence and prevalence of RRT patients in Serbia are rising continuously, while the mortality rate is falling. More favorable conditions for dialysis treatment have brought about significant improvement in the results over the last 10 years.     

Mortality risk in hemodialysis patients according to anemia control and erythropoietin dosing

There is no consensus about the toxicity of erythropoiesis‐stimulating agents among hemodialysis patients. We aimed to calculate the risk of death according to anemia control and erythropoietin (EPO) dosing among end‐stage renal disease patients undergoing hemodialysis. We retrospectively studied 156 end‐stage renal disease patients on hemodialysis from a single renal unit during 12 months. Participants were classified according to anemia control into four groups: excellent (A), good (B), moderate (C) and bad (D) control. They were also classified according to EPO dosing into two groups: usual and high EPO dosing. The Cox proportional hazards regression model, adjusted for the difference in age, sex, time on dialysis, comorbidity, albumin, and Kt/V index, was performed to calculate the risk of death according to anemia control and EPO dosing profiles. Multivariate analysis by backward stepwise logistic regression was used to calculate the risk of death according to the variables that differed in the comparison between survivors and nonsurvivors. The hazard ratio of death was not significant according to anemia control profile C/D vs. A/B, but hazard ratio was 2.967 (95% confidence interval [CI] = 1.132–7.777; P = 0.027) for high EPO dosing profile patients. The multivariate analysis showed comorbidity (odds ratio [OR] = 8.958; 95% CI = 2.843–26.223; P < 0.001], high EPO dosing profile (OR = 5.172; 95% CI = 1.663–16,081; P = 0.005), age (OR = 1.056; 95% CI = 1.020–1.094; P = 0.002), and mean hemoglobin (OR = 0.435; 95% CI = 0.267–0.709; P = 0.001) to be predictive of death. Even though we cannot conclude that mortality risk is due to EPO toxicity, hemodialysis patients using high EPO dosing must be seen as at risk.     

Causes and consequences of inflammation on anemia management in hemodialysis patients

Inflammation is common among hemodialysis patients, and evidence is accumulating to suggest that inflammation is a major contributor to morbidity and mortality. Several factors have been suggested as potential causes of inflammation, including infections and the atherosclerosis process, as well as etiologies directly related to kidney disease such as reduced renal function and dialysis. Among several inflammatory biomarkers investigated, serum C-reactive protein (CRP) is the most widely used. In hemodialysis patients, raised CRP levels have been shown to be predictive of cardiovascular events, hospitalization, and all-cause and cardiovascular mortality. Elevated CRP levels may correlate with comorbidities and intercurrent events, all of which may impact the response to erythropoiesis-stimulating agents (ESAs) and lead to higher ESA doses. Most dialysis facilities do not routinely measure CRP, despite recommendations by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative. Regular measurement of CRP levels may help providers to understand change in ESA dosing and identify patients at risk for cardiovascular events. This review explores the inter-relationships between inflammation, CRP levels, and anemia management in patients receiving hemodialysis.     

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.     

Evolution of diagnostic reference levels in Spanish intraoral radiology

A total of 16 175 official reports of quality assurance on dental radiodiagnostic surgeries from 16 Spanish autonomous regions compiled during 2002-09 were studied to determine the evolution of diagnostic reference levels (DRLs) for obtaining a diagnostic image in the normal conditions of clinical practice in Spanish dental clinics. A DRL of 3.1 mGy was set in 2009, which represents a 35.4 % decrease compared with the dose determined in 2002 (4.8 mGy). During the same period, the mean dose fell by only 17.2 %. The DRL recommended by the European Union in 2004 for intraoral radiology is 4 mGy, and this study shows that 83.4 % of the installations used a dose below this. Of the installations using indirect or direct digital systems 1.1 and 1.2 %, respectively, used doses higher than those recommended, while 14.2 % of those using radiographic film exceeded this limit.     

Post‐hemodialysis dosing of 1 vs. 2 g of ceftazidime in anuric end‐stage renal disease patients on low‐flux dialysis and its pharmacodynamic implications on clinical use

Ceftazidime is a cost‐effective antimicrobial against Gram‐negative pathogens associated with sepsis in end‐stage renal disease (ESRD) hemodialysis patients with potential for wider use with the advent of ceftazidime‐avibactam. Dosing ceftazidime post‐hemodialysis appears attractive and convenient, but limited in vivo data on pharmacodynamic efficacy (PE) attainment, defined as >70% of the interdialytic period drug concentrations exceed susceptible pathogens minimal inhibitory concentrations (MICs) (%TMIC), warrants further assessment. We therefore evaluated PE and tolerability of 1 against 2 g regime in anuric ESRD patients on low‐flux hemodialysis. Two doses of 1 or 2 g ceftazidime were administered post‐hemodialysis prior to 48‐ and 72‐hour interdialytic intervals in ESRD inpatients without active infections. Peak and trough concentrations (mg/L) were assayed using a validated liquid chromatography–tandem mass spectrometry method. Proportion of patients achieving PE for known pathogens with MICs ≤ 8 mg/L and adverse effects were assessed. Six (43%) and eight (57%) adult patients received 1 and 2 g dose, respectively. Median (25th–75th percentile), peak, 48‐ and 72‐hour trough ceftazidime concentrations were 78 (60–98) vs. 158 (128–196), 37 (23–37) vs. 49 (39–71), and 13 (12–20) vs. 26 (21–41) mg/L, respectively, resulting in 100% TMIC for both doses. One patient on the 1‐g dose experienced mild pruritus. Reliable and safe PE attainment over both 48‐ and 72‐hour interdialytic interval was achievable with 1 g of ceftazidime dosed post‐hemodialysis. The 2 g dose was equally effective and well tolerated but may not be necessary. These findings need validation in non‐anuric patients, high‐flux hemodialysis, and during avibactam co‐administration.     

Relationship between erythropoietin resistance index and left ventricular mass and function and cardiovascular events in patients on chronic hemodialysis

The response to erythropoietin (EPO) treatment varies considerably in individual patients on chronic hemodialysis. The EPO resistance index (ERI) has been considered useful to assess the EPO resistance and can be easily calculated in the clinic. The aim of this study was to investigate the association between ERI and left ventricular mass (LVM) and function and to determine whether ERI was associated with cardiovascular events in patients on hemodialysis. This study was designed prospectively. Clinical, laboratory, and echocardiographic variables were assessed in 72 patients on hemodialysis. The ERI was determined as the weekly weight-adjusted dose of EPO (U/kg/week) divided by hemoglobin concentration (g/dL). Patients were divided into three groups by tertiles of ERI. Patients with higher tertiles of ERI had a higher LVM index and lower LV ejection fraction compared with those with lower tertiles of ERI (P = 0.019 and P = 0.030, respectively). The median follow-up period was 53 months. The Kaplan-Meier plot showed increased frequency of cardiovascular events in patients with higher tertiles of ERI, compared with those with lower tertiles of ERI (P = 0.011, log-rank test). The multivariate Cox proportional hazard models showed that the ERI was the significant independent predictor of cardiovascular events (HR 3.00, 95% CI, 1.04-8.62, P = 0.042). Our data show that ERI was related with LVM index, LV systolic function and cardiovascular events in patients with hemodialysis. By monitoring of ERI, early identification of the EPO resistance may be helpful to predict the cardiovascular risk in hemodialysis patients.     

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.     

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.