Stability of Target Hemoglobin Levels during the First Year of Epoetin Treatment in Patients with Chronic Kidney Disease

Abstract

Background and Objectives: Instability of hemoglobin levels during epoetin therapy is a new problem in hemodialysis. We evaluated extent and correlates of time in target, that is, the time spent with hemoglobin >11 g/dl during the first year of epoetin and its association with renal survival.Design, Setting, Participants, & Measurements: Data were collected in 917 visits for 12.0 mo in 119 patients with chronic kidney disease; thereafter, patients started renal survival analysis for 10.1 mo. At baseline, hemoglobin was 10.0 ؎ 0.8 g/dl and GFR was 22.1 ؎ 14.2 ml/min per 1.73 m 2 . Results: Hemoglobin target, reached in 1.5 mo, was steadily maintained in only 24% of patients. Time in target was not merely due to differences in time to target; after first achievement of target, in fact, a reduction of hemoglobin <11 g/dl occurred in 51% of patients. At multivariate analysis, male gender, basal GFR and hemoglobin levels, first epoetin dose, and iron supplementation were directly associated with length of time in target. A lower risk for renal death (dialysis n ‫؍‬ 53; death n ‫؍‬ 8) was detected in the higher tertile of time in target (11.3 mo) versus lower tertile (3.2 mo). This difference persisted at Cox analysis after adjustment for age, gender, GFR, BP, and proteinuria.Conclusions: In chronic kidney disease, time in target during the first year of epoetin therapy is frequently short depending not only on time to target but also on post-target hemoglobin reductions, correlates with male gender, timing, and intensity of initial therapy and is coupled with better renal survival.

Epoetin Therapy and Hemoglobin Level Variability in Nondialysis Patients with Chronic Kidney Disease

“…Outcome variables during the baseline period were the measures of Hb variability, such as Hb fluctuations (18,19), residual standard deviation (SD) (20), within-patient SD for Hb (29), and time in target (21). We also calculated the area under the curve for Hb (Hb-AUC) to define the time-weighted average of Hb levels.…”

“…Indeed, on the one hand, omission of therapy with EPO is frequent throughout the whole spectrum of CKD (3)(4)(5)(6)(7)(8)(11)(12)(13)(14)(15)(16); on the other hand, several studies have reported that in treated patients, transitory reductions of Hb levels below target range are common and associated with worse outcome (17)(18)(19)(20)(21)(22). Specifically, in nondialysis patients with CKD, we found that intrapatient Hb variability occurred frequently, with most patients showing a limited extent of time spent with Hb at target (time in target), and that short time in target is associated with lower renal survival (21). Our previous study, however, left unanswered a critical question: Whether stability of Hb depends on individual responsiveness to EPO or intensity of therapeutic intervention.…”

Association Between Haemoglobin Variability and Clinical Outcomes in Chronic Kidney Disease

“…Interestingly, in one report, the risk of developing haemoglobin variability was greater with long-acting ESAs (Boudville et al, 2009). De Nicola and colleagues did not find any association between long-acting ESAs versus erythropoietin and haemoglobin variability (De Nicola et al, 2007). However, they observed that baseline haemoglobin level, first dose of ESA and initial iron supplementation were directly associated with the length of time-in-target haemoglobin.…”

“…al., 2008). In a study of 119 non-dialysis CKD patients, male gender was directly associated with increased time-intarget haemoglobin (De Nicola et al, 2007).…”

“…Various studies have reported that young age is a risk factor for haemoglobin variability (De Nicola et al, 2007;Eckardt et al, 2010). Boudville and colleagues reported that the odds of haemoglobin variability decreased by 11% with each 10-yr increment in age (Boudville et al, 2009).…”