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Journal ArticleDOI

Associations Between Changes in Hemoglobin and Administered Erythropoiesis-Stimulating Agent and Survival in Hemodialysis Patients

TL;DR: In this article, longitudinal associations between survival and quarterly (13-wk averaged) hemoglobin values and administered erythropoiesis-stimulating agents (ESA) dose in a 2-yr (July 2001 to June 2003) cohort of 58,058 maintenance hemodialysis patients from a large dialysis organization (DaVita) in the United States.
Abstract: Although treating anemia of chronic kidney disease by erythropoiesis-stimulating agents (ESA) may improve survival, most studies have examined associations between baseline hemoglobin values and survival and ignored variations in clinical and laboratory measures over time. It is not clear whether longitudinal changes in hemoglobin or administered ESA have meaningful associations with survival after adjustment for time-varying confounders. With the use of time-dependent Cox regression models, longitudinal associations were examined between survival and quarterly (13-wk averaged) hemoglobin values and administered ESA dose in a 2-yr (July 2001 to June 2003) cohort of 58,058 maintenance hemodialysis patients from a large dialysis organization (DaVita) in the United States. After time-dependent and multivariate adjustment for case mix, quarterly varying administered intravenous iron and ESA doses, iron markers, and nutritional status, hemoglobin levels between 12 and 13 g/dl were associated with the greatest survival. Among prevalent patients, the lower range of the recommended Kidney Disease Quality Outcomes Initiative hemoglobin target (11 to 11.5 g/dl) was associated with a higher death risk compared with the 11.5- to 12-g/dl range. A decrease or increase in hemoglobin over time was associated with higher or lower death risk, respectively, independent of baseline hemoglobin. Administration of any dose of ESA was associated with better survival, whereas among those who received ESA, requiring higher doses were surrogates of higher death risk. In this observational study, greater survival was associated with a baseline hemoglobin between 12 and 13 g/dl, treatment with ESA, and rising hemoglobin. Falling hemoglobin and requiring higher ESA doses were associated with decreased survival. Randomized clinical trials are required to examine these associations.

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Journal ArticleDOI
TL;DR: In patients with chronic kidney disease, early complete correction of anemia does not reduce the risk of cardiovascular events and there was no significant difference in the combined incidence of adverse events between the two groups.
Abstract: BACKGROUND Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established. METHODS We randomly assigned 603 patients with an estimated glomerular filtration rate (GFR) of 15.0 to 35.0 ml per minute per 1.73 m 2 of body-surface area and mild-to-moderate anemia (hemoglobin level, 11.0 to 12.5 g per deciliter) to a target hemoglobin value in the normal range (13.0 to 15.0 g per deciliter, group 1) or the subnormal range (10.5 to 11.5 g per deciliter, group 2). Subcutaneous erythropoietin (epoetin beta) was initiated at randomization (group 1) or only after the hemoglobin level fell below 10.5 g per deciliter (group 2). The primary end point was a composite of eight cardiovascular events; secondary end points included left ventricular mass index, quality-of-life scores, and the progression of chronic kidney disease. RESULTS During the 3-year study, complete correction of anemia did not affect the likelihood of a first cardiovascular event (58 events in group 1 vs. 47 events in group 2; hazard ratio, 0.78; 95% confidence interval, 0.53 to 1.14; P = 0.20). Left ventricular mass index remained stable in both groups. The mean estimated GFR was 24.9 ml per minute in group 1 and 24.2 ml per minute in group 2 at baseline and decreased by 3.6 and 3.1 ml per minute per year, respectively (P = 0.40). Dialysis was required in more patients in group 1 than in group 2 (127 vs. 111, P = 0.03). General health and physical function improved significantly (P = 0.003 and P<0.001, respectively, in group 1, as compared with group 2). There was no significant difference in the combined incidence of adverse events between the two groups, but hypertensive episodes and headaches were more prevalent in group 1. CONCLUSIONS In patients with chronic kidney disease, early complete correction of anemia does not reduce the risk of cardiovascular events. (ClinicalTrials.gov number, NCT00321919.)

1,955 citations

Journal ArticleDOI
TL;DR: Associations between high serum parathyroid hormone and increased death risk were masked by case-mix characteristics of MHD patients, and Administration of any dose of paricalcitol was associated with improved survival in time-varying models.

866 citations

Journal ArticleDOI
01 Jan 2012
TL;DR: The use of ESAs and other agents to treat anemia in CKD and methods for Guideline Development suggest that red cell transfusion is a viable treatment option.
Abstract: 282 Summary of Recommendation Statements 283 Chapter 1: Diagnosis and evaluation of anemia in CKD 288 Chapter 2: Use of iron to treat anemia in CKD 292 Chapter 3: Use of ESAs and other agents to treat anemia in CKD 299 Chapter 4: Red cell transfusion to treat anemia in CKD 311 Methods for Guideline Development 317 Biographic and Disclosure Information 324

712 citations


Cites background from "Associations Between Changes in Hem..."

  • ...The idea that anemia should be corrected completely was based on pathophysiologic considerations and the demonstration by numerous observational studies of an inverse association between Hb concentrations up into the normal range and intermediate outcomes such as left ventricular hypertrophy,(110) as well as hard patient outcomes such as cardiovascular events, hospital admission,(114) and death.(115,116) Of note, a recent study also showed that CKD 5D patients with naturally occurring Hb concentrations greater than 12 g/dl (120 g/l) were not at increased mortality risk....

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Journal ArticleDOI
TL;DR: This study demonstrates that patients achieving their target had better outcomes than those who did not; and among subjects who achieved their randomized target, no increased risk associated with the higher hemoglobin goal was detected.

479 citations


Cites background from "Associations Between Changes in Hem..."

  • ...Two observational studies have demonstrated relationships between epoetin dose requirements and clinical factors such as age, diabetes mellitus, and serum ferritin.(12,13) This potential for confounding limits the ability of a data set with a single hemoglobin target or dosing strategy to discern whether the risk detected is associated with dose or with clinical factors necessitating the dose....

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References
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Journal ArticleDOI
TL;DR: In patients with clinically evident congestive heart failure or ischemic heart disease who are receiving hemodialysis, administration of epoetin to raise their hematocrit to 42 percent is not recommended.
Abstract: Background In patients with end-stage renal disease, anemia develops as a result of erythropoietin deficiency, and recombinant human erythropoietin (epoetin) is prescribed to correct the anemia partially. We examined the risks and benefits of normalizing the hematocrit in patients with cardiac disease who were undergoing hemodialysis. Methods We studied 1233 patients with clinical evidence of congestive heart failure or ischemic heart disease who were undergoing hemodialysis: 618 patients were assigned to receive increasing doses of epoetin to achieve and maintain a hematocrit of 42 percent, and 615 were assigned to receive doses of epoetin sufficient to maintain a hematocrit of 30 percent throughout the study. The median duration of treatment was 14 months. The primary end point was the length of time to death or a first nonfatal myocardial infarction. Results After 29 months, there were 183 deaths and 19 first nonfatal myocardial infarctions among the patients in the normal-hematocrit group and 150 deat...

1,944 citations

Journal ArticleDOI

854 citations


"Associations Between Changes in Hem..." refers background in this paper

  • ...The K/DOQI guidelines (14) and the European Best Practice Guidelines (15) have recommended a hemoglobin target of 11 to 12 g/dl and 11 g/dl, respectively....

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Journal ArticleDOI
TL;DR: In this historical cohort study, chronic hemodialysis patients in the group that received injectable vitamin D had a significant survival advantage over patients who did not, and the benefit of injectableitamin D was evident in 48 of 49 strata examined, including those with low serum levels of intact parathyroid hormone and elevated levels of serum calcium and phosphorus.
Abstract: Patients with ESRD commonly experience secondary hyperparathyroidism, a condition primarily managed with activated injectable vitamin D. The biologic effects of vitamin D, however, are widespread, and it is possible that activated injectable vitamin D alters survival in ESRD. This hypothesis was tested in a historical cohort study of incident hemodialysis patients who lived throughout the United States between January 1996 and December 1999. The primary outcome was 2-yr survival among those who survived for at least 90 d after initiation of chronic hemodialysis. During this period, 51,037 chronic hemodialysis patients survived for at least 90 d from the initiation of hemodialysis, and in the ensuing 2 yr, 37,173 received activated injectable vitamin D and 13,864 did not. At 2 yr, mortality rates were 13.8/100 person-years in the group that received injectable vitamin D compared with 28.6/100 person-years in the group that did not (P < 0.001). Cox proportional hazards analyses adjusting for several potential confounders and examining injectable vitamin D therapy as a time-dependent exposure suggested that compared with patients who did not receive injectable vitamin D, the 2-yr survival advantage associated with the group that did receive injectable vitamin D was 20% (hazard ratio, 0.80; 95% confidence interval, 0.76 to 0.83). The incidence of cardiovascular-related mortality was 7.6/100 person-years in the injectable vitamin D group, compared with 14.6/100 person-years in the non-vitamin D group (P < 0.001). The benefit of injectable vitamin D was evident in 48 of 49 strata examined, including those with low serum levels of intact parathyroid hormone and elevated levels of serum calcium and phosphorus, situations in which injectable vitamin D is often withheld. Repeating the entire analysis using marginal structural models to adjust for time-dependent confounding by indication yielded a survival advantage of 26% (hazard ratio, 0.74; 95% confidence interval, 0.71 to 0.79) associated with the injectable vitamin D group. In this historical cohort study, chronic hemodialysis patients in the group that received injectable vitamin D had a significant survival advantage over patients who did not. Randomized clinical trials would permit definitive conclusions.

781 citations


"Associations Between Changes in Hem..." refers background in this paper

  • ...Moreover, most of these studies examined old cohorts of dialysis patients before the contemporary era of dialysis technique and dose and more universal use of intravenous iron and vitamin D analogs, which per se may be associated with improved survival (16,28)....

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  • ...Although use of such novel epidemiologic tools as marginal structural modeling may mitigate the degree of bias by indication (28), such models were not examined in our study....

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Journal ArticleDOI
TL;DR: Anemia, an easily reversible feature of end- stage renal disease, is an independent risk factor for clinical and echocardiographic cardiac disease, as well as mortality in end-stage renal disease patients.

736 citations

Journal ArticleDOI
TL;DR: Overall adverse event rates were similar in both target groups; higher rates of skeletal pain, surgery, and dizziness were seen in the lower target group, and headache and cerebrovascular events wereseen in the higher target group.
Abstract: It is unclear whether physiologic hemoglobin targets lead to cardiac benefit in incident hemodialysis patients without symptomatic heart disease and left ventricular dilation. In this randomized, double-blind study, lower (9.5 to 11.5 g/dl) and higher (13.5 to 14.5 g/dl) hemoglobin targets were generated with epoetin α over 24 wk and maintained for an additional 72 wk. Major eligibility criteria included recent hemodialysis initiation and absence of symptomatic cardiac disease and left ventricular dilation. The primary outcome measure was left ventricular volume index (LVVI). The study enrolled 596 patients. Mean age, duration of dialysis therapy, baseline predialysis hemoglobin, and LVVI were 50.8 yr, 0.8 yr, 11.0 g/dl, and 69 ml/m 2 , respectively; 18% had diabetic nephropathy. Mean hemoglobin levels in the higher and lower target groups were 13.3 and 10.9 g/dl, respectively, at 24 wk. Percentage changes in LVVI between baseline and last value were similar (7.6% in the higher and 8.3% in the lower target group) as were the changes in left ventricular mass index (16.8 versus 14.2%). For the secondary outcomes, the only between-group difference was an improved SF-36 Vitality score in the higher versus the lower target group (1.21 versus −2.31; P = 0.036). Overall adverse event rates were similar in both target groups; higher ( P

361 citations


"Associations Between Changes in Hem..." refers background in this paper

  • ...Amelioration of anemia by ESA results in improved quality of life in patients with CKD (9,23) and may confer protection against cardiovascular disease (24,25)....

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  • ...34 12,000 to 18,000 10,751 (19) 2,533 (24) 1,122 (11) 12....

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