Hemoglobin Variability Does Not Predict Mortality in European Hemodialysis Patients

Abstract

Patients with CKD exhibit significant within-patient hemoglobin (Hb) level variability, especially with the use of erythropoiesis stimulating agents (ESAs) and iron. Analyses of dialysis cohorts in the United States produced conflicting results regarding the association of Hb variability with patient outcomes. Here, we determined Hb variability in 5037 European hemodialysis (HD) patients treated over 2 years to identify predictors of high variability and to evaluate its association with all-cause and cardiovascular disease (CVD) mortality. We assessed Hb variability with various methods using SD, residual SD, time-in-target (11.0 to 12.5 g/dl), fluctuation across thresholds, and area under the curve (AUC). Hb variability was significantly greater among incident patients than prevalent patients. Compared with previously described cohorts in the United States, residual SD was similar but fluctuations above target were less frequent. Using logistic regression, age, body mass index, CVD history, dialysis vintage, serum albumin, Hb, angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) use, ESA use, dialysis access type, dialysis access change, and hospitalizations were significant predictors of high variability. Multivariable adjusted Cox regression showed that SD, residual SD, time-in-target, and AUC did not predict all-cause or CVD mortality during a median follow-up of 12.4 months (IQR: 7.7 to 17.4). However, patients with consistently low levels of Hb (Ͻ11 g/dl) and those who fluctuated between the target range and Ͻ11 g/dl had increased risks for death (RR 2.34; 95% CI: 1.24 to 4.41 and RR 1.74; 95% CI: 1.00 to 3.04, respectively). In conclusion, although Hb variability is common in European HD patients, it does not independently predict mortality.

Association Between Haemoglobin Variability and Clinical Outcomes in Chronic Kidney Disease

“…Each 3-mo increment in the duration of ESA therapy decreased the risk of haemoglobin variability by 6%. In a study involving 5,037 ESKD patients on haemodialysis, the risk of developing haemoglobin variability was more than twice in patients on ESAs, compared to those not on ESAs (Eckardt et al, 2010). These findings suggest that the need of ESA rather than ESA therapy per se leads to haemoglobin variability (See Table 1).…”

“…al., 2009;). On the other hand, 82 to 90% of ESKD patients on dialysis exhibit haemoglobin variability (Ebben et al, 2006;Eckardt et. al., 2010;Gilbertson et.…”

“…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).…”

“…Eckardt and colleagues studied the magnitude and frequency of haemoglobin variability as a quantitative index by integrating the area under the curve (AUC) between measured haemoglobin values and the mean haemoglobin concentration (Eckardt et al, 2010). High degree of haemoglobin variability was defined as AUC >50 th percentile.…”

Erythropoiesis-Stimulating Agents in Renal Medicine

“…When the Hb level exceeds the target, the ESA dose should be reduced without discontinuing treatment in order to avoid an excessive decrease in the Hb level that can only be corrected with higher ESA doses, because this may lead to Hb cycling. This cause-effect relationship is far from proven, but it has been related to greater mortality at the patient [35] and facility [36] level, although a recent observational study of 5,037 European HD patients found that the risk for mortality was only higher in patients with persistently low Hb levels (Ͻ11 g/dL) or levels that fluctuated between the target range and Ͻ11 g/dL [37].…”