Age and anemia management: relationship of hemoglobin levels with mortality might differ between elderly and nonelderly hemodialysis patients

Abstract

Background: The elderly hemodialyzed population is growing. However, little is known about the relationship between hemoglobin level and survival according to age. We investigated the effect of age on the relationship between hemoglobin and survival within the Japan Dialysis Outcomes and Practice Patterns Study (DOPPS) cohort.

Methods: We enrolled the entire Japan DOPPS phases 3 and 4 population. Patients were divided by the age of 75 years into two groups. Cox's proportional hazard model was used with hemoglobin at every 4 months treated as a time-dependent variable. The interaction of age and hemoglobin was analyzed.

Results: We included 3341 patients in the analyses. The primary outcome occurred in 567 patients during the median follow-up of 2.64 years. Hemoglobin of entire population was 10.3 ± 1.3 g/dL. The median of epoetin dose was 3000 IU/week. Interaction was found between ages stratified by the age of 75 years and hemoglobin values (P = 0.045) with use of Cox's proportional hazard model. The nonelderly population had poorer prognosis with hemoglobin <10 g/dL, while elderly population only with hemoglobin <9 g/dL. For both hemoglobin strata <9, ≥9 and <10 g/dL, interactions between age and hemoglobin were significant. Subgroup analysis indicated that interaction between age and Hb levels was observed only in the nondiabetic nephropathy group. Several sensitivity analyses demonstrated a similar trend with the original analyses and reinforced the robustness.

Conclusions: The elderly population might tolerate low hemoglobin levels. Our findings open the way for further investigation of individualized anemia management.

Keywords: aged population; anemia management; individualized therapy; mortality.

FIGURE 1:

Flow diagram of the analyzed population. J-DOPPS phases 3 and 4 were potential population for the present study. Among phase 3 patients, 1121 patients were continuously followed-up into the phase 4 period. After exclusion, a complete data set was created for 3341 patients. J-DOPPS: the Japan Dialysis Outcomes and Practice Patterns Study.

FIGURE 2:

Effect of age on optimal Hb target ranges (cutoff age: 75 years). The HR of mortality for patients in each Hb group versus reference was assessed using Cox models adjusted for sex, years on dialysis, primary disease (diabetic nephropathy), smoking, 13 comorbidities (coronary artery disease, cancer, other cardiovascular disease, cerebrovascular disease, congestive heart failure, diabetes, gastrointestinal bleeding, hypertension, lung disease, neurologic disorder, psychological disorder, peripheral vascular disease and recurrent cellulitis), body mass index, single-pool Kt/V, albumin, C-reactive protein, adjusted Ca, serum P, total cholesterol, ferritin and epoetin dose of ≥4500 IU/week without (A) or with (B) inverse propensity treatment weighting. P for trend indicates the significance across Hb strata within each age group, whereas P for interaction indicates the significance between both age groups in each Hb strata. Hb, hemoglobin; HR, hazard ratio; 95% CI, 95% confidence interval.

FIGURE 3:

Analyses stratified by the primary diagnosis of diabetic nephropathy were performed for the groups where the cutoff age was 75 years. (A) Analyses for patients without diabetic nephropathy; (B) analyses for patients with diabetic nephropathy. The HR of mortality for patients in each Hb group versus reference was assessed using Cox models adjusted for sex, years on dialysis, smoking, 13 comorbidities (coronary artery disease, cancer, other cardiovascular disease, cerebrovascular disease, congestive heart failure, diabetes, gastrointestinal bleeding, hypertension, lung disease, neurological disorder, psychological disorder, peripheral vascular disease and recurrent cellulitis), body mass index, single-pool Kt/V, albumin, C-reactive protein, adjusted Ca, serum P, total cholesterol, ferritin and epoetin dose of ≥4500 IU/week with inverse propensity treatment weighting. P for trend indicates the significance across Hb strata within each age group, whereas P for interaction indicates the significance between both age groups in each Hb strata. Hb, hemoglobin; HR, hazard ratio; 95% CI, 95% confidence interval.