epoetin-alfa and Diabetes-Mellitus

Topics: Anemia; Darbepoetin alfa; Diabetes Mellitus; Epoetin Alfa; Erythropoietin; Heart Failure; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Treatment Outcome

The CHOIR trial in anemic patients with chronic kidney disease compared epoetin-alfa treatment with low (11.3 g/l) and high (13.5 g/l) hemoglobin targets on the composite end point of death, hospitalization for heart failure, stroke, and myocardial infarction. However, other anemia management trials in patients with chronic kidney disease found there was increased risk when hemoglobin is targeted above 13 g/dl. In this secondary analysis of the CHOIR trial, we compared outcomes among the subgroups of patients with diabetes and heart failure to describe the comparative relationship of treatment to these two different hemoglobin goals. By Cox regression analysis, there was no increased risk associated with the higher hemoglobin target among patients with heart failure. In patients without heart failure, however, the hazard ratio (1.86) associated with the higher target was significant. Comparing survival curves in an unadjusted model, patients with diabetes did not have a greater hazard associated with the higher target. Subjects without diabetes had a significantly greater hazard in the high as compared to the low target, but the interaction between diabetes and the target was not significant. We suggest that the increased risks associated with higher hemoglobin targets are not clinically apparent among subgroups with greater mortality risk. These differential outcomes underscore the need for dedicated trials in these subpopulations.

Topics: Aged; Aged, 80 and over; Anemia; Chronic Disease; Comorbidity; Diabetes Mellitus; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Regression Analysis; Retrospective Studies; Survival Analysis; Treatment Outcome

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.

Topics: Diabetes Mellitus; Electronic Health Records; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Hypertension; Kidney Failure, Chronic; Male; Models, Biological; Practice Guidelines as Topic; Predictive Value of Tests; Recombinant Proteins; Renal Dialysis; United States

Anemia is common in chronic kidney disease (CKD). The CHOIR study found increased risk of a composite cardiovascular outcome when anemia was treated with epoetin-alfa to a target hemoglobin level of 13.5 as compared with 11.3 g/dl. Whether this increase applies to all patient subgroups equally is unclear. We discuss an analysis by Szczech and colleagues of the effects of the higher hemoglobin target in CKD patients with diabetes mellitus or congestive heart failure.

Topics: Anemia; Chronic Disease; Diabetes Mellitus; Epoetin Alfa; Erythropoietin; Heart Failure; Hemoglobins; Humans; Kidney Diseases; Recombinant Proteins

Darbepoetin alpha is effective for renal anemia when epoetin is insufficient. We previously reported that the dose conversion ratio from epoetin alpha to darbepoetin alpha was 1:350.5 after 24 weeks of follow-up. This study assessed the conversion ratio in stable Japanese hemodialysis patients after 52 weeks.. A total of 104 hemodialysis patients who were stable on intravenous epoetin alpha were switched to intravenous darbepoetin alpha according to the 1:200 rule. Then they were followed for 52 weeks to assess changes of hemoglobin and the darbepoetin alpha dose.. Eighty-five patients completed the study. Their hemoglobin increased very rapidly during the first 8 weeks. The final conversion ratio was 1:286.6 at 52 weeks. Darbepoetin alpha showed similar efficacy in diabetics and non-diabetics. Patients switching from a high epoetin alpha dose (> or =4500 IU/week) had a higher conversion ratio compared with those switching from a low dose (<4500 IU/week).. The dose conversion ratio of 1:200 was unsuitable and led to a rapid increase of hemoglobin. A conversion ratio of 1:250 to 1:300 should be employed when switching from epoetin alpha to darbepoetin alpha in Japanese patients.

Topics: Aged; Anemia; Asian People; Biomarkers; Darbepoetin alfa; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Dosage Calculations; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Japan; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome

In patients with diabetes mellitus, hemoglobin A(1c) (A1C) is commonly interpreted as a measure of long-term glycemic control, reflecting a mean glucose level over the previous 2-3 months. Although some reports suggest that treatment with recombinant erythropoietin may affect A1C values in patients undergoing hemodialysis, we know of no evidence to support this interaction in patients with chronic renal insufficiency who are not undergoing hemodialysis. In addition, we know of no evidence specific to the treatment effect of epoetin alfa and/or darbepoetin alfa on A1C. We describe a 64-year-old man with diabetes, chronic kidney disease, and anemia who was treated consecutively with epoetin alfa and darbepoetin alfa and experienced a temporal reduction in A1C level to a nadir of 4.4%. Throughout approximately 3 years of treatment with these erythropoietin analogs, the patient's total daily dose of insulin was reduced in response to his decreasing A1C values, despite elevated blood glucose levels and the absence of patient-reported hypoglycemic events. Five months after the patient's erythropoietin therapy was discontinued, his A1C value increased to 8.8%, leading us to conclude that management of the insulin dose may have been different without the falsely lowered A1C levels. Use of the Naranjo adverse drug reaction probability scale indicated a probable association between this patient's reduced A1C levels and erythropoietin therapy. This case demonstrates that both epoetin alfa and darbepoetin alfa may artificially lower A1C levels in a patient with diabetes who is not undergoing dialysis, and therefore this finding can be interpreted as a class effect. Clinicians should be aware of factors that affect A1C values, specifically erythrocyte life span. In patients receiving erythropoietin, therapeutic decisions should be based on A1C and glucose levels, as well as patient symptoms suggestive of hypo- or hyperglycemia, to avoid therapy changes that could complicate disease management.

Topics: Anemia; Darbepoetin alfa; Diabetes Mellitus; Diabetic Nephropathies; Diagnostic Errors; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Glycated Hemoglobin; Hematinics; Humans; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

Anemia is a common complication of advancing chronic kidney disease, yet little is known about the consistency of anemia treatment before end-stage renal disease (ESRD) and mortality on dialysis therapy.. We studied 89,193 incident Medicare patients with ESRD in 1995 to 1997 aged 67 plus years with claims 2 years before their dialysis therapy initiation. Patients were classified as follows: no epoetin, 25% or less (least consistent), greater than 25% to 50%, greater than 50% to 75%, and greater than 75% (most consistent) epoetin treatment in the available months from the first pre-ESRD epoetin dose to the first ESRD service date. Cox regression modeled the risk for 1-year death in the post-ESRD period, adjusting for age, sex, race, diabetic status, albumin level, and incidence year.. Sixty percent of patients had hematocrits less than 30% at ESRD initiation, yet only 15.6% (N = 13,877) had epoetin claims before ESRD. The most consistent epoetin treatment group had hematocrits increase from 27.5% to 30.8% (P < 0.0001) by month 4 of treatment. Patients with the most consistent epoetin treatment had a greater mean hematocrit (29.2% +/- 0.11%; P < 0.0001) and albumin level (3.31 +/- 0.01 g/dL [33.1 g/L]) at initiation than those with the least consistent treatment (28.1% +/- 0.10% and 3.21 +/- 0.01 g/dL [32.1 g/L], respectively). The relative risk for death in patients with the least consistent versus the most consistent (the reference) epoetin treatment was 1.460 (95% CI, 1.245 to 1.713; P < 0.0001) 1 year after the first ESRD service date.. Elderly patients with consistent pre-ESRD epoetin treatment had lower risks for death in the first year of dialysis therapy after ESRD initiation.

Topics: Aged; Anemia; Diabetes Complications; Diabetes Mellitus; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Indices; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Male; Models, Statistical; Mortality; Racial Groups; Recombinant Proteins; Renal Dialysis; Reproducibility of Results; Serum Albumin; Sex Factors; Survival Rate