CHICAGO — Maintaining a lower hemoglobin level may help prevent morbidity and mortality in patients with chronic kidney disease, according to a study of 1,432 patients randomized to two different hemoglobin goals.
Almost half of patients with stage 3–5 chronic kidney disease (CKD) have anemia, and nephrologists know that treating anemia with erythropoietin and iron “improves quality of life, well-being, exercise tolerance, and lowers the risk of transfusions,” said Dr. Ajay Singh, who presented late-breaking results of the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) study at a meeting on clinical nephrology sponsored by the National Kidney Foundation.
A deficiency of erythropoietin, which is produced by the kidneys, is known to contribute to anemia. Iron deficiency also plays a role, noted Dr. Singh, director of the dialysis unit at Brigham and Women's Hospital, Boston.
But researchers have not yet elucidated the optimal target hemoglobin level for CKD patients. Dr. Singh and his associates conducted a randomized, controlled trial of 1,432 patients with CKD. The patients were randomized to one of two groups, with a target hemoglobin of either 13.5 g/dL or 11.3 g/dL. The groups had similar baseline characteristics: About half of those in each group had diabetes, and about one-third had hypertension.
Patients were followed weekly, for a median of 16 months, to assess how many in each group reached a primary composite end point of death, MI, stroke, or severe heart failure requiring hospital admission. Patients in both groups received an average dose of 8,000 U of erythropoietin subcutaneously every week. To achieve the hemoglobin levels specified in the trial, some patients were switched to every-other-week dosing.
Patients also received iron supplementation, as indicated, according to the standard of care.
The patients randomized to the lower hemoglobin level were significantly less likely to reach the primary composite end point, compared with those randomized to the higher hemoglobin level.
Further analysis of the data showed that death and heart failure were driving the composite end point, rather than an increased incidence of stroke or MI. No difference was seen between the groups in reaching the secondary composite end point: all-cause mortality, change in hemoglobin level or hematocrit, or development of heart failure.
The physiologic mechanisms underlying the findings have not yet been worked out. “The biologic mechanisms are unclear,” Dr. Singh said in an interview.
It is not yet known whether the poorer outcomes seen in the high-hemoglobin group were the result of the higher level of hemoglobin itself, the use of erythropoietin to achieve this higher hemoglobin level, or other factors. “It seems to be a phenomenon related to kidney disease,” he added.