Serum Albumin Is Strongly Associated with Erythropoietin Sensitivity in Hemodialysis Patients

Abstract

Background and objectives: In hemodialysis patients, the hematological response to erythropoietin (epo) is variable and clinical factors that explain this variability are incompletely understood. We tested the hypothesis that the variability in hemoglobin (Hgb) response (epo sensitivity) is determined by key nutritional, inflammation, and oxidative stress markers.Design, setting, participants, & measurements: Eighty-two consecutive patients on hemodialysis had 3 consecutive monthly predialysis evaluations of Hgb, total white blood cell (WBC) count, serum albumin, malondialdehyde (MDA), and monocyte chemoattractant protein-1 (MCP1). We analyzed the time course of Hgb in relationship to serum albumin, WBC, MDA, MCP1, epo and iron administration, and tests of iron sufficiency in a linear growth curve model.Results: Subjects with higher Hgb had a fall in Hgb and vice versa, regressing to a mean Hgb (SD) of 11.8 g/dl (1.8 g/dl). Whereas the average slope of Hgb was flat, the SD of slopes was 0.63 g/dl, which explained 39% of the variance in Hgb. Nonuse of epo was associated with a mean Hgb change of ؊0.18 g/dl (95% confidence interval [CI] ؊0.26 to ؊0.10) per 10,000 IU epo/mo (P < 0.05). Epo use was associated with steeper rate of change at 0.04 g/dl per mo per 10,000 IU (95% CI 0.01 to 0.07) (P < 0.01). Hgb at baseline was 0.73 g/dl higher for each 1-g/dl increase in albumin, and the rate of change increased by 0.49 g/dl per mo for each 1-g/dl increase in albumin concentration. WBC, MDA, or MCP1 had no role in predicting the baseline Hgb or its change over time.Conclusions: Serum albumin concentration is an important predictor of both baseline Hgb and epo sensitivity in chronic hemodialysis patients. Factors that improve serum albumin may also improve Hgb in hemodialysis patients.

Iron, Inflammation, Dialysis Adequacy, Nutritional Status, and Hyperparathyroidism Modify Erythropoietic Response

“…Serum Ferr and TSat have been used as the two primary markers of iron available for erythropoiesis. However, many studies have failed to show the effect that these markers have on the erythropoietic response (7,16,(25)(26)(27). Our analysis indicates that both markers are associated with the moderation of the erythropoietic response.…”

“…Among these factors, iron stores are most thoroughly described (7)(8)(9)(10)(11). Other factors include inflammation (12,13), adequacy of dialysis (14,15), nutritional status (16), and hyperparathyroidism (17).…”

Individual Response Variations to Erythropoietin Stimulating Agents in Patients on Maintenance Hemodialysis.

“…Therefore, albumin level could be considered a marker of nutritional status as well as inflammation. Malnutrition and inflammation can cause hypoalbuminemia and also suppress erythropoeisis since the elevated levels of cytokines particularly IL-1, mediates acute phase response, enhances CRP production and reduces albumin level and transferrin synthesis [19]. Low level of transferrin prevents transportation of iron to the hematopoietic sites and leads to suppression of Hgb synthesis as well as hyporesponsiveness to ESA [41].…”

“…Main factors associated with ESA resistance include iron deficiency [18] low serum albumin level [19], malnutrition [20], hyperparathyroidism [21], suboptimal dialysis [22]; however, ESA resistance is still an incompletely understood problem. Therefore, identifying the factors that associate with ESA resistance is important not only in reducing the costs associated with the treatment, but also possibly in influencing patients' mortality risks.…”

Individualizing Decision-Making—Resurrecting the Doctor-Patient Relationship in the Anemia Debate

“…Therefore, ESA hyporesponse is dynamic and must be evaluated on an ongoing basis. One study found that an acute-phase reactant, serum albumin concentration, tracks closely with ESA response (24). Larger studies are needed to determine whether serum albumin and change in serum albumin can be used to track ESA responsiveness and individualize therapy.…”