High Hb Group Research Articles

The Combination of Uric Acid and Hemoglobin Levels Predicts the Incident Risk of Ischemic Heart Disease More Than Uric Acid Alone in Non-Diabetic Koreans: A Longitudinal Study Using National Health Insurance Data.

Uric acid has been related to cardiovascular disease (CVD). Recently, slightly elevated hemoglobin (Hb) was also shown to be associated with CVD. We retrospectively investigated the joint effect of uric acid and elevated Hb by comparing normal-range uric acid alone on incident ischemic heart disease (IHD) risk in a large cohort of non-diabetic Korean adults using National Health Insurance data. We assessed 16,786 participants without diabetes (8595 men and 8191 women) using extensive cohort data. High Hb was defined as ≥16.4 g/dL in men and 13.8 g/dL in women (>75th percentile). We analyzed the data using two different methods. First, the participants were divided into quartiles according to uric acid levels. Second, subjects were also divided into quartiles: reference (group 1), high uric acid and normal Hb (group 2), normal uric acid and high Hb (group 3), and normal uric acid and high Hb (group 4). We evaluated hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox regression analysis over a 50-month follow-up. During the follow-up, 345 (1.9%) participants developed IHD. In the analysis using both uric acid and Hb, compared with the reference group, the HRs for IHD were 1.37 (95% CI, 1.01-1.86) in the second group, 1.63 (95% CI, 1.21-2.21) in the third group, and 1.86 (95% CI, 1.30-2.67) in the fourth group after adjusting for IHD risk factors. Subsequently, patients with high uric acid are more likely to develop incident IHD than control patients. Moreover, we confirmed the joint effects of high uric acid and high hemoglobin on incident IHD. Awareness of these interactions is essential for clinicians. Risk factor management and screening for IHD are part of the routine management of patients with high uric acid and Hb.

Correlation Between Hemoglobin Levels and Polycystic Ovary Syndrome Metabolic Disorder.

The purpose of this study was to explore the relationship between hemoglobin levels and metabolic disorders in patients with PCOS. A total of 573 patients were selected, based on the hemoglobin level; 342 patients with PCOS were divided into two groups as follows: Group A (normal Hb group, n = 269) and Group B (high Hb group, n = 73); 231 non-PCOS patients were divided into two groups as follows: Group C (normal Hb group, n = 199), and Group D (high Hb group, n = 32). The general information, glucose and lipid metabolism indicators, and uric acid levels of all patients were compiled for data analysis. (1) Hb, HGB concentration in mean red blood cells and RDW in PCOS patients were higher than those in non-PCOS patients, and MCV was lower than that in non-PCOS patients (P < 0.05); (2) Compared with Group A, patients in Group B had higher BMI, Hb, 2-hPG, FINS, 2-hINS, HOMA-IR, LDL-C, and uric acid levels while the QUICKI was lower; in Group C, the age, FSH, HDL-C, and LDL-C were higher, and AMH, BMI, T, TG, and uric acid level were lower (P<0.05); compared with Group D, AMH, BMI, FINS, HOMA-IR, TG, uric acid level increased, while age, FSH, and QUICKI decreased in Group B; and Hb and T decreased in Group C (P<0.05); (3) Pearson's correlation analysis indicated that Hb in PCOS patients was positively correlated with BMI, FPG, 2-hPG, FINS, 2-hINS, and HOMA-IR, and negatively correlated with the QUICKI (P<0.05); (4) Multi-factor logistic regression analysis suggested that the high Hb level in PCOS patients was an independent risk factor of IR (P<0.05). Hb level in patients with PCOS was associated with BMI and glucose metabolism indicators; a high Hb level may be an independent risk factor for IR.

Impact of anemia treatment for left ventricular hypertrophy using long-acting erythropoietin-stimulating agents from the pre-dialysis to maintenance dialysis period in patients with chronic kidney disease, retrospective longitudinal cohort study

BackgroundAnemia in patients with chronic kidney disease (p-CKDs) may initiate or exacerbate left ventricular hypertrophy (LVH). This study aimed to determine whether treatment using long-acting erythropoietin-stimulating agents (L-ESAs) is independently associated with LVH during the pre-dialysis to maintenance dialysis period in p-CKDs.MethodsPhysical and laboratory examinations were performed 120 days before initiating dialysis in p-CKDs (baseline). To evaluate the left ventricular mass index (LVMI) after starting dialysis, the mean hemoglobin (Hb) was defined as the average at the start of dialysis and 6 months after starting dialysis. Changes in the LVMI were observed in three groups according to mean Hb levels (Hb < 10.1, 10.1 < Hb < 11.0, and Hb > 11.0 g/dL for Groups 1, 2, and 3, respectively). LVMI was evaluated using echocardiography at the pre-dialysis, initiation, and maintenance dialysis periods.ResultsA lower LVMI at dialysis initiation and an improvement in LVMI were detected in the highest tertile group of mean Hb (11.0 g/dl). Consequently, in the high Hb group (Hb level > 11.0 g/dl), LVMI remained low from dialysis initiation until after 6 months.The relationship between Hb and LVMI was not significant; however, a constant correlation with β ≥ 0.4 in the absolute value was maintained.ConclusionL-ESAs may correlate with Hb and LVMI after administration, independent of the baseline LVMI and Hb values. These findings have therapeutic implications in the treatment strategies for p-CKDs during the pre-dialysis to maintenance dialysis period.

Abstract 13183: Persistent Anemia Was Associated With Higher Long-Term Mortality in Patients With Chronic Kidney Disease Following Primary Percutaneous Coronary Intervention

Background: Anemia is one of the most common complications of chronic kidney disease (CKD), renal anemia, which has a significant link with increased risk of the morbidity, as well as the mortality of cardiovascular disease. However, the prognostic implication of the temporal change of anemia status has been rarely addressed, especially in secondary prevention of coronary artery disease (CAD). Methods and Results: This long-term (median follow-up range: 5.7 years) single center observational study involved consecutive 416 patients with CKD over stage 3 (defined by eGFR&lt;60 ml/1.72/m 2 ) who underwent percutaneous coronary intervention (PCI) for the first time since 2003 to 2018. All-cause death was set as an endpoint. Participants were divided into 4 groups by the median of hemoglobin (Hb) at PCI (baseline, 12.0 mg/dl) and 8.1±2.1 months after PCI (follow-up, 12.7 mg/dl), respectively: Groups of Continuously high-Hb (n=146), Increased-Hb (n=51), Attenuated-Hb (n=61) and Persistently low-Hb (n=158). Categorized Cox proportional hazard analysis with setting Continuously high-Hb group as a reference showed a significantly increased risk of all-cause death in groups of Attenuated- (Hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.3-5.2, p=0.01) and Persistently low-Hb (HR 2.6, 95%CI 1.4-4.8, p=0.002), respectively, while similar in Increased-Hb group (HR 1.1, 95%CI 0.3-3.2, p&gt;0.5) (Figure) . Conclusion: This study showed a significant association between the reduced Hb overtime and increased mortality risk in patients with CKD and CAD, which might potentially indicate a prognostic merit of the intervention for renal anemia in this population.

Longitudinal Effect of Hemoglobin Concentration With Incident Ischemic Heart Disease According to Hepatic Steatosis Status Among Koreans.

Background: An increased hemoglobin (Hb) level may have detrimental effects on hepatic steatosis (HS) as well as cardiovascular disease (CVD). We investigated Hb's effect on incident ischemic heart disease (IHD) risk in the context of hepatic steatosis (HS).Methods: We assessed 17,521 non-diabetic participants and retrospectively screened for IHD using the Korea National Health Insurance data. High Hb was defined as Hb levels ≥16.3 g/dL in men and 13.9 g/dL in women (>75th percentile). The participants were divided into five groups: reference (group 1), mild HS only (group 2), mild HS and high Hb (group 3), severe HS only (group 4), and severe HS and high Hb (group 5). We assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional hazards regression models over 50 months from the baseline survey.Results: During the follow-up period, 330 (1.9%) participants developed IHD (310 angina pectoris and 20 myocardial infarction). Compared with the reference group (group 1), the HRs for IHD were 1.04 (95% CI, 0.75–1.46) in group 2, 1.14 (95% CI, 0.70–1.85) in group 3, 1.58 (95% CI, 1.08–2.32) in group 4, and 1.79 (95% CI, 1.15–2.80) in group 5, after adjusting for IHD risk factors.Conclusions: We found the combined effect of HS and Hb levels on the incidence of IHD.

POS-288 THE BURDEN OF HEART FAILURE IN PATIENTS WITH NON–DIALYSIS-DEPENDENT ANAEMIA OF CHRONIC KIDNEY DISEASE RECEIVING ERYTHROPOIESIS-STIMULATING AGENTS: A SYSTEMATIC LITERATURE REVIEW

Anaemia of chronic kidney disease (CKD) is associated with significant morbidity and increased mortality, particularly cardiovascular complications such as heart failure (HF). We performed a systematic literature review of the treatment options for anaemia of CKD in non-dialysis-dependent (NDD) patients. This abstract reports HF-related outcomes from clinical trials in patients with NDD anaemia of CKD. We identified randomised controlled trials (RCTs; phase 2+) for erythropoiesis-stimulating agents (ESAs) for the treatment of anaemia of CKD in adults, from electronic databases (Embase®, MEDLINE®, Cochrane library), grey literature and other sources. Outcomes were not used in the search to avoid excluding eligible trials. Other criteria were, English publications between database inception and 23 January 2020 (search date). Risk of bias was assessed using a quality appraisal checklist. Descriptive statistics assessed study and patient characteristics and HF-related outcomes in ESA trials. A total of 4,024 abstracts were screened and 325 full-text publications reviewed; 38 ESA RCTs that randomised 12,594 patients with NDD-CKD and anaemia met the inclusion criteria. Mean age range was 46.0–84.4 years; median study duration was 50.5 weeks. Most trials (24; 63%) were open-label; 9 (24%) were double-blind. Twenty-seven trials were determined to have a risk of bias but remained in the descriptive assessment. Comparative trials most often investigated darbepoetin alfa or its biosimilar (DPO; 12 trials), epoetin alfa (EPO A) or its biosimilar and recombinant human erythropoietin (16 trials) and continuous erythropoietin receptor activator (3 trials). HF-related outcomes were reported in 19 trials, including as the primary endpoint in 7 trials. HF occurrence as an adverse event (AE; 15 trials), change in left ventricular mass index (LVMI; 7 trials), and hospitalisation related to HF (1 trial) were reported. Heterogeneity in outcome definitions and reporting was observed. One trial comparing a low haemoglobin (Hb) target (9.0–11.0 g/dL) with low dose ESA vs. a high Hb target (11.0–13.0 g/dL) with DPO reported significant LVMI reduction from baseline in the high Hb group (−7.8 g/m2; 95% CI: −12.1 to −3.6 g/m2; P<0.001). Another study reported a significantly reduced LVMI (P=0.02) with EPO A (−5.7±14.2 g/m2) and DPO (−5.6±15.8 g/m2) vs. controls (no ESA); however, no difference in LVMI decrease was observed between treatment arms. One study included hospitalisation for congestive HF without renal replacement therapy as a component of the composite primary endpoint. Of the 222 composite events, 101 (45.5%) hospitalisations for congestive HF were reported in the high and low Hb EPO A treatment arms combined. The proportions of patients from the safety populations (n=13,082) with a congestive HF AE ranged from 0% to 9.0% across trials and treatment arms. Findings of this review suggested a potentially high occurrence of HF-related outcomes, such as LVMI reduction and hospitalisations. We observed substantial heterogeneity in the reporting and results of HF-related outcomes in ESA RCTs. Information from observational studies may also be needed to fully characterise the burden of HF in patients with NDD-CKD and anaemia on ESA treatment.

Anemia Predicts Poor Outcomes in Patients with HBV-Related Decompensated Cirrhosis.

Anemia is common in patients with severe chronic liver disease, but its role in HBV-related decompensated cirrhosis (DeCi) is still unclear. We therefore aimed to assess the impact of anemia on prognosis in HBV-DeCi patients. One hundred thirty-three patients diagnosed with HBV-DeCi were retrospectively collected. A total of 113 (85.0%) patients suffered from anemia in our cohort. The low hemoglobin (Hb) level group exhibited a significantly increased 28-day mortality rate compared with the high Hb group. Hb level was a predictor of 28-day mortality in HBV-DeCi patients. Reduced Hb levels were associated with unfavorable prognosis in HBV-DeCi patients, and more attention should be paid to anemia in routine clinical assessments of liver cirrhosis.

The effect of maintaining high hemoglobin levels on long-term kidney function in kidney transplant recipients: a randomized controlled trial.

BackgroundPosttransplant anemia may be a major determinant of chronic allograft nephropathy. However, the impact of correcting anemia on graft function remains controversial.MethodsA 3-year follow-up of an open-label, multicenter, randomized controlled trial involving kidney transplantation recipients examined whether sustained maintenance of target hemoglobin (Hb) concentrations at a high level (12.5–13.5 g/dL, n = 64) with either darbepoetin alfa or epoetin beta pegol would slow the graft function decline rate as the primary efficacy endpoint, compared with maintenance of a low Hb concentration (10.5–11.5 g/dL, n = 63).ResultsThe mean blood pressures in the two groups were well controlled throughout the study. In the high Hb group, mean Hb concentrations increased to >12 g/dL at 3 months, reaching the target range at 18 months. At the end of this study (36 months), the mean Hb concentration was 12.8 ± 0.7 g/dL in the high Hb group and 11.5 ± 1.2 g/dL in the low Hb group. The decline rate of the estimated glomerular filtration (eGFR) rate was considerably greater in the low Hb group (ΔeGFR, −5.1 ± 9.5 mL/min/1.73 m2) than in the high Hb group (−1.0 ± 8.4 mL/min/1.73 m2) (P = 0.02). Of note, only a few high Hb patients developed cardiovascular events and returned to hemodialysis, but the low Hb patients did not.ConclusionThis prospective study suggests that correcting anemia to the target Hb level range (12.5–13.5 g/dL) slows renal function deterioration by >3 years in the chronic phase of allograft nephropathy.

Heart failure and anemia: Effects on prognostic variables

BackgroundAnemia is frequent in heart failure (HF), and it is associated with higher mortality. The predictive power of established HF prognostic parameters in anemic HF patients is unknown. MethodsClinical, laboratory, echocardiographic and cardiopulmonary-exercise-test (CPET) data were analyzed in 3913 HF patients grouped according to hemoglobin (Hb) values. 248 (6%), 857 (22%), 2160 (55%) and 648 (17%) patients had very low (<11g/dL), low (11–12 for females, 11–13 for males), normal (12–15 for females, 13–15 for males) and high (>15) Hb, respectively. ResultsMedian follow-up was 1363days (606–1883). CPETs were always performed safely. Hb was related to prognosis (Hazard ratio (HR)=0.864). No prognostic difference was observed between normal and high Hb groups. Peak oxygen consumption (VO2), ventilatory efficiency (VE/VCO2 slope), plasma sodium concentration, ejection fraction (LVEF), kidney function and Hb were independently related to prognosis in the entire population. Considering Hb groups separately, peakVO2 (very low Hb HR=0.549, low Hb HR=0.613, normal Hb HR=0.618, high Hb HR=0.542) and LVEF (very low Hb HR=0.49, low Hb HR=0.692, normal Hb HR=0.697, high Hb HR=0.694) maintained their prognostic roles. High VE/VCO2 slope was associated with poor prognosis only in patients with low and normal Hb. ConclusionsAnemic HF patients have a worse prognosis, but CPET can be safely performed. PeakVO2 and LVEF, but not VE/VCO2 slope, maintain their prognostic power also in HF patients with Hb<11g/dL, suggesting CPET use and a multiparametric approach in HF patients with low Hb. However, the prognostic effect of an anemia-oriented follow-up is unknown.

Discharge hemoglobin and outcome in patients with acute nonvariceal upper gastrointestinal bleeding.

Background and study aims: Many patients with acute gastrointestinal bleeding present with anemia and frequently require red blood cell (RBC) transfusion. A restrictive transfusion strategy and a low hemoglobin (Hb) threshold for transfusion had been shown to produce acceptable outcomes in patients with acute upper gastrointestinal bleeding. However, most patients are discharged with mild anemia owing to the restricted volume of packed RBCs (pRBCs). We investigated whether discharge Hb influences the outcome in patients with acute nonvariceal upper gastrointestinal bleeding. Patients and methods: We retrospectively analyzed patients with upper gastrointestinal bleeding who had received pRBCs during hospitalization between January 2012 and January 2014. Patients with variceal bleeding, malignant lesion, stroke, or cardiovascular disease were excluded. We divided the patients into 2 groups, low (8 g/dL ≤ Hb < 10 g/dL) and high (Hb ≥ 10 [g/dL]) discharge Hb, and compared the clinical course and Hb changes between these groups. Results: A total of 102 patients met the inclusion criteria. Fifty patients were discharged with Hb levels < 10 g/dL, whereas 52 were discharged with Hb levels > 10 g/dL. Patients in the low Hb group had a lower consumption of pRBCs and shorter hospital stay than did those in the high Hb group. The Hb levels were not fully recovered at outpatient follow-up until 7 days after discharge; however, most patients showed Hb recovery at 45 days after discharge. The rate of rebleeding after discharge was not significantly different between the 2 groups. Conclusions: In patients with acute upper gastrointestinal bleeding, a discharge Hb between 8 and 10 g/dL was linked to favorable outcomes on outpatient follow-up. Most patients recovered from anemia without any critical complication within 45 days after discharge.

Efficacy of Erythropoietin-Beta Injections During Autologous Blood Donation Before Spinal Deformity Surgery in Children and Teenagers.

Retrospective observational study OBJECTIVE.: To clarify the efficacy of recombinant human erythropoietin-beta (EPO-beta) injections during autologous blood donation (ABD) before spinal deformity surgery in children and teenagers. ABD is preferred for spinal deformity surgery. A few studies have assessed the usefulness of preoperative ABD with EPO-beta in anemic patients. Fifty-six spinal deformity surgery patients (41 females, 15 males; median age: 15 yrs; range, 5-19 yrs) underwent preoperative ABD. ABD was performed weekly according to the patient's body weight with a subcutaneous EPO-beta injection (24,000 U). The collected blood volumes were compared among the low hemoglobin (low-Hb) (<13 g/dL), mid-Hb (13-13.9 g/dL), and high-Hb (≥14 g/dL) groups using the Kruskal-Wallis test. The effects of EPO-beta injection on the Hb levels were estimated using a linear mixed model. The patients underwent a median of four ABD collections (range, two to six). The median collected volume per ABD was 200 mL (range, 40-400 mL). The median total blood collection was 700 mL (range, 160-1,350 mL); the corresponding values were 700 mL, 700 mL, and 800 mL in the low-Hb, mid-Hb, and high-Hb groups, respectively (P = 0.964). The median blood loss was 500 mL (range, 10-2,940 mL); 53 out of 55 patients (96%) did not require unplanned allogeneic transfusion, including 11 out of 12 (92%) cases with blood loss >1,000 mL. The additional recovery of Hb levels with one EPO-beta injection was 0.29 ± 0.14 g/dL (P = 0.039) after adjusting for confounding factors. ABD with an EPO-beta injection is useful for avoiding allogeneic transfusion during spinal deformity surgery in children and teenagers, and patients in the low-Hb group achieved ABD volumes equivalent to those in the high-Hb group. Thus, an additional recovery of Hb levels of 0.29 g/dL per injection can be expected after 1 week. 4.

Rationale and study design of a randomized controlled trial to assess the effects of maintaining hemoglobin levels using darbepoetin alfa on prevention of development of end-stage kidney disease in non-diabetic CKD patients (PREDICT Trial).

Anemia associated with high mortality is a common complication of chronic kidney disease (CKD). Target hemoglobin (Hb) levels for CKD treatment remain controversial: Recent guidelines recommend a maximum of 13 g/dL to avoid increased risk of CVD. However, some smaller studies show slower progression of renal function loss with high Hb targets. Recently, darbepoetin alfa targeting Hb 11-13 g/dL was reported to improve renal composite outcome of Japanese patients compared with a low Hb group maintained at 9.0-11.0 g/dL using epoetin alfa (HR 0.66; 95% CI 0.47-0.93). The high Hb group showed significant reduction of left ventricular mass index and improved quality of life. Sub-analysis revealed greater beneficial effects in non-diabetic stage 5 CKD patients. This randomized controlled trial, PREDICT, aims to confirm the impact of targeting Hb levels of 11-13 g/dL using darbepoetin alfa with reference to a low Hb target of 9-11 g/dL. We calculated the number of subjects (N = 440) necessary to detect a statistically significant level of α = 0.05 (two-sided) and statistical power of 80% for a minimum follow-up period of 2 years on the basis of a previous study. The study enrolled 498 non-diabetic Japanese patients with eGFR 8-20 mL/min/1.73 m(2). The primary outcome is a composite renal endpoint (starting chronic dialysis, transplantation, eGFR 6 mL/min/1.73 m(2) or less, 50% decrease in eGFR). Average follow-up period is 2 years and the study ends in 2016. PREDICT will determine the optimum target Hb for Japanese patients with non-diabetic CKD. (ClinicalTrials.gov No. NCT01581073).

High Hemoglobin Levels Maintained by an Erythropoiesis-Stimulating Agent Improve Renal Survival in Patients with Severe Renal Impairment.

Our goal was to investigate the effect modification of maintaining a high Hb target range through erythropoiesis-stimulating agent therapy on the renal outcome with respect to chronic kidney disease (CKD) stage and concurrent diabetes condition in patients with CKD. We used data from a previously reported randomized controlled trial involving 321 CKD patients not on dialysis, with Hb levels of <10 g/dL, and serum creatinine (Cr) of 2.0 to 6.0 mg/dL, and in which maintaining Hb levels at 11.0-13.0 g/dL with darbepoetin-α (High Hb group) resulted in a greater renal protective effect than maintaining Hb levels at 9.0-11.0 g/dL with epoetin-α (Low Hb group). We conducted a post-hoc analysis of the effects of baseline CKD stage and concurrent diabetic condition on the renal composite endpoint, consisting of death, initiation of renal replacement therapy, and doubling of the serum Cr level. Both groups with stage 4 CKD had a 3-year cumulative renal survival rate of 53.8%, whereas in patients with stage 5 CKD, the rate in the High Hb group (31.0%) was significantly (P = 0.012) higher than that in the Low Hb group (19.1%). The observations made in patients with stage 5 CKD were maintained on further analysis of non-diabetic patients, but were not seen in those with diabetes or stage 4 CKD. These results suggest that in patients with stage 5 CKD, especially those without diabetes, achieving a higher target Hb level with erythropoiesis-stimulating agents is associated with a greater renoprotective effect.

The pre-transplant anemic condition is independent of long-term outcome in living-related kidney transplantation

The relationship between pre-transplant Hemoglobin (Hb) concentration and long-term outcome of living-related kidney transplantation is far from well addressed. A retrospective cohort study was conducted by reviewing the medical profile of the patients who received living-related kidney transplantations at our center from January 2006 to January 2013. Patients were divided into two groups: high Hb group (≥10 g/dL) and low Hb group (<10 g/dL). Cox regression model was utilized to analyze the effect of pre-transplant hemoglobin concentration on the patient and graft survival. About 422 patients were of Hb level <10 g/dL (78.30 ± 14.18 g/dL), 280 were >10 g/dL (116.2 ± 14.43 g/dL) (p < 0.001). In a follow-up of 35.34 ± 18.12 months, we did not find any difference in serum creatinine between the two groups. Low Hb concentration is not associated with increased risk of developing DGF (HR = 1.186, 95% CI: 0.53–2.654), acute rejection (HR = 1.338, 95% CI: 0.919–1.947), overall infection (HR = 1.263, 95% CI: 0.847–1.885) nor perioperational infection (HR = 1.019, 95% CI: 0.513–2.026). Though we detected a trend that low Hb level group were of higher incidence of patient death and graft failure, the two groups did not differ significantly (2.38% vs. 0.71%, p = 0.096; and 4.04% vs. 2.14%, p = 0.165, respectively). Cox regression model revealed that pre-transplant Hb level <10 g/dL was independent of increased overall mortality (HR = 3.379; 95% CI: 0.706–17.172) and increased death censored allograft failure risk (HR = 1.556; 95% CI: 0.595–4.069). Pre-transplant Hb concentration <10 g/dL is independent of poor long-term outcome of living-related kidney transplantation.

Effect of anemia correction to the modestly high hemoglobin level in patients with chronic kidney disease on left ventricular hypertrophy

Background and purposeTo assess effects of long-term anemia management on left ventricular hypertrophy in patients with chronic kidney disease (CKD) not on dialysis, we performed secondary outcome analyses of a randomized controlled study that evaluated effects of anemia management with erythropoiesis stimulating agents in this population. Methods and subjectsSubjects [hemoglobin (Hb)<10.0g/dL, 2.0≤serum creatinine<6.0mg/dL] were randomized either to high Hb (11.0≤target Hb≤13.0g/dL with darbepoetin alfa), or to low Hb group (9.0≤target Hb≤11.0g/dL with recombinant human erythropoietin), and followed up to 48 weeks. Data from echocardiographic evaluation and values of neurohumoral factors associated with heart failure were assessed in subjects whose data were evaluable both at the baseline and at the end point. ResultsThe high Hb group achieved target range Hb levels (12.1±1.1g/dL, at 32 weeks, N=111), which was significantly higher (p<0.001) than the low Hb group (N=95). Though blood pressure and renal function changes were similar between the groups, left ventricular diastolic dimension was significantly decreased only in the high Hb group (p<0.001), and the change in left ventricular mass index (LVMI) correlated coarsely but significantly with the achieved Hb levels (r=0.147, p=0.032). The higher Hb levels were associated with greater reduction in LVMI and left ventricular wall thickness, and the lower Hb levels with the greater increase in human arterial- or brain natriuretic polypeptide levels. ConclusionsAnemia correction targeting modestly higher Hb levels better preserves cardiac function in CKD patients not on dialysis.

Hemoglobin Targets for Chronic Kidney Disease Patients with Anemia: A Systematic Review and Meta-analysis

BackgroundNumerous studies have identified a relationship between hemoglobin (Hb) levels and mortality in patients with chronic kidney disease (CKD), which have raised concerns about the optimal Hb targets in correction of anemia. Our study is designed to investigate the potential effects of targeted Hb levels, aiming to give some evidence for therapy of renal anemia.Methodology/Principal FindingsA comprehensive search of Medline, Embase and the Cochrane Database of Systematic Reviews was performed in December 2011 and updated in February 2012 for any new trials. Randomized trials designed to evaluate effects of high (generally the Hb about 13.0 g/dL) and low Hb (generally the Hb about 10.0 g/dL) targets on clinical outcomes in CKD patients with anemia were collected. All statistical analysis was calculated using the RevMan software available free from the Cochrane Collaboration. 24 trials involving 10361 patients were identified. Our findings demonstrated a statistically significant increased risk of mortality in the high Hb levels (RR 1.18; 95% CI 1.02 to 1.37) while the high and low Hb groups were both treated with ESAs. Overall, compared with low Hb levels, high Hb levels are associated with increased risk of hypertension (RR 1.40; 95% CI 1.11 to 1.75), stroke (RR 1.73; 95% CI 1.31 to 2.29), and hospitalizations (RR 1.07; 95% CI 1.01 to 1.14). However, there are no significant differences in the risk of non-fatal myocardial infarction (RR 1. 13; 95% CI 0.79 to 1.61) and renal replacement therapy (RR 1. 00; 95% CI 0.85 to 1.18).Conclusions/SignificancesTargeting low Hb levels are beneficial to CKD patients especially in the predialysis population. The optimal Hb targets to aim for in CKD patients and at what Hb level the risks of adverse events begin to increase remain elusive. Future studies are still needed to elucidate these questions.

High Target Hemoglobin With Erythropoiesis‐Stimulating Agents Has Advantages in the Renal Function of Non‐Dialysis Chronic Kidney Disease Patients

We investigated the long-term effects of maintaining high hemoglobin (Hb) on renal function in patients with chronic kidney disease not on dialysis. Subjects (Hb < 10 g/dL and serum creatinine (Cr) 2-6 mg/dL) were randomized to either a high Hb group (N = 161, 11.0 ≤ Hb < 13.0 g/dL) receiving darbepoetin alfa or to a low Hb group (N = 160, 9.0 ≤ Hb < 11.0 g/dL) with epoetin alfa, stratified according to baseline Hb and serum Cr levels, comorbidity of diabetes, and study centers. Primary endpoints were composites of the following events: doubling of serum Cr, initiation of dialysis, renal transplantation, or death. Three-year cumulative renal survival rates (95% CI) were 39.9% (30.7-49.1%) and 32.4% (24.0-40.8%) in the high and low Hb groups, respectively (log-rank test; P = 0.111). A Cox proportional-hazards model adjusted by age, sex and the randomization factors showed a significantly lower event rate in the high Hb group (P = 0.035). The estimated hazard ratio (95% CI) for the high versus the low Hb group was 0.71 (0.52-0.98), the risk reduction was 29% in the high Hb group. Incidences of serious adverse cardiovascular events did not differ significantly between the high and low Hb groups (3.1% and 4.4%, respectively). No safety issues were noted in either group. Maintaining higher Hb levels with darbepoetin alfa better preserved renal function in patients with chronic kidney disease not on dialysis.

Association of haemoglobin with ambulatory arterial stiffness index in untreated essential hypertensive patients without anaemia

ObjectiveIncreased haemoglobin (Hb) levels are known to be associated with increased cardiovascular events and mortality in hypertensive patients, but the underlying mechanism remains unclear. Meanwhile, increased Ambulatory Arterial Stiffness Index...

Positive Outcomes of High Hemoglobin Target in Patients With Chronic Kidney Disease Not on Dialysis: A Randomized Controlled Study

Correcting anemia in patients with chronic kidney disease (CKD) to higher hemoglobin (Hb) levels may be associated with increased risk. No optimal target for Hb has been established. This controlled study examined 321 patients with CKD who were not on dialysis, had a Hb level of <10g/dL, and a serum creatinine of 2.0 to 6.0mg/dL. They were randomized into two target Hb groups: 161 to high Hb (11.0-13.0g/dL) to receive darbepoetin alfa and low Hb to 160 (9.0-11.0g/dL) to receive recombinant erythropoietin. The study lasted 48weeks. Of 154 and 153 patients with adverse events, cardiovascular adverse events developed in 42 and 51 patients in the high and low Hb groups, respectively, with no significant difference in the incidence. All quality of life scores improved in the high Hb group and vitality improved significantly more with high Hb (P=0.025). The left ventricular mass index (LVMI) remained stable in the low Hb group, but there was a significant decrease in LVMI in the high group (P<0.001). There were no safety concerns with targeting a higher Hb level during the 48weeks of this study. Patients with a higher Hb target had comparatively better outcomes with respect to quality of life and LVMI.

Association of Hemoglobin with Ambulatory Arterial Stiffness Index in Untreated Essential Hypertensive Patients Without Anemia

Increased hemoglobin (Hb) levels are known to be associated with increased cardiovascular events and mortality in hypertensive patients, but the underlying mechanism remains unclear. However, an increased Ambulatory Arterial Stiffness Index (AASI), the surrogate maker of arterial stiffness, has been proven to be an independent predictor of cardiovascular disease. This pilot study evaluated the association between Hb and AASI in untreated essential hypertensive patients without anemia. A total of 566 untreated essential hypertensive patients without anemia were divided into Normal-Hb and High-Hb groups according to their Hb levels. The AASI and its symmetric calculation (Sym_AASI) were derived from 24h-Ambulatory Blood Pressure Monitoring (24h-ABPM). A multivariable linear regression analysis was performed to determine the relationship between Hb and AASI, Sym_AASI. High-Hb group (n=127) showed higher AASI and Sym_AASI (0.51±0.11 vs 0.43±0.12, p<0.001; 0.33±0.10 vs 0.27±0.08, p<0.001) compared to Normal-Hb group (n=439). Univariate correlation analysis showed that Hb levels were positively related to AASI and Sym_AASI values (r=0.459, p<0.001; r=0.353, p<0.001). After adjustment for age, sex, BMI, current smoker, eGFR, uric acid, total cholesterol, high-density lipoprotein, 24h-SBP, 24h-PP and dipper status, Hb persisted as a independent determinant of AASI and Sym_AASI (β=0.402, p<0.001 and β=0.298, p<0.001, respectively). High hemoglobin seems be to associated with increased AASI in untreated essential hypertensive patients without anemia.