Japanese haemodialysis anaemia management practices and outcomes (1999-2006): results from the DOPPS

Abstract

Background: Japanese haemodialysis (HD) patients not only have a very low mortality and hospitalization risk but also low haemoglobin (Hb) levels. Internationally, anaemia is associated with mortality, hospitalization and health-related quality of life (QoL) measures of HD patients.

Methods: Longitudinal data collected from 1999 to 2006 from 60 to 64 representative Japanese dialysis units participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS) were used to describe anaemia management practices and outcomes for Japanese HD patients.

Results: From 1999 to 2006, patient mean Hb increased from 9.7 g/dl to 10.4 g/dl, and the percentage of facilities with median Hb >or=10 g/dl increased from 27% to 75%. Hb was measured in the supine position for 90% of patients, resulting in substantially lower reported Hb values than those seen in other countries. As of 2006, erythropoietin (Epo) was prescribed to 83% of HD patients; mean Epo dose was 5231 units/week; intravenous (IV) iron use was 33% and median IV iron dose was 160 mg/month. Many patient- and facility-level factors were significantly related to higher Hb. A consistent overall pattern of lower mortality risk with higher baseline Hb levels was seen (RR = 0.89 per 1 g/dl higher Hb, P = 0.003). Facilities with median Hb >or=10.4 displayed a lower mortality risk (RR = 0.77, P = 0.03) versus facility median Hb <10.4 g/dl. Lower Hb levels were not significantly related to hospitalization risk, but were associated with lower QoL scores.

Conclusions: These results provide detailed information on anaemia management practices in Japan and the relationships of anaemia control with outcomes, with implications of anaemia management worldwide.

Fig. 1

(A) Distribution of haemoglobin concentrations among prevalent Japanese haemodialysis patients with ESRD >180 days in DOPPS I (1999), DOPPS II (2002) and DOPPS III (2006). The results for each study phase are based upon a point-prevalent cross-section of HD patients with ESRD >180 days in DOPPS I (n = 1996), DOPPS II (n = 1581) or DOPPS III (n = 1656). The standard deviation ranged from 1.35 in DOPPS I to 1.23–1.26 in DOPPS II and III. (B) Distribution of facility median haemoglobin concentrations among Japanese dialysis units in DOPPS I (1999), DOPPS II (2002), and DOPPS III (2006). Facility median haemoglobin concentrations were determined for a point-prevalent cross-section of HD patients having ESRD >180 days in each participating DOPPS dialysis unit at the start of each study phase; n = 64 facilities for DOPPS I, n = 60 for DOPPS II and n = 61 for DOPPS III.

Fig. 2

Epo dosing practices for Epo-treated HD patients in DOPPS III. (A) Distribution of facility mean Epo dose (Epo units/week) among DOPPS III dialysis units. Facility mean Epo dose (units/week) was calculated based on the number of Epo units/week given to Epo-treated patients from a point-prevalent cross-section of HD patients having ESRD >180 days in each participating DOPPS dialysis unit at the start of DOPPS III; n = 61 facilities. (B) Percentage of Epo-treated HD patients receiving one, two or three Epo doses per week in DOPPS III. Results are based upon a point-prevalent cross-section of Japanese HD patients having ESRD >180 days at the start of DOPPS III; n = 1412 patients. (C) Distribution of patient Epo doses (Epo units/week) in DOPPS III for patients receiving one, two or three Epo doses per week. Results are based on a point-prevalent cross-section of Japanese HD patients having ESRD >180 days at the start of DOPPS III; n = 1412 patients.

Fig. 3

(A) Distribution of facility IV iron use among Japanese dialysis units in DOPPS I (1999), DOPPS II (2002) and DOPPS III (2006). The percentage of patients within a facility using IV iron was determined for a point-prevalent cross-section of HD patients having ESRD >180 days in each participating DOPPS dialysis unit at the start of each study phase; n = 63 facilities for DOPPS I, n = 60 for DOPPS II and n = 61 for DOPPS III. (B) Distribution of the number of IV iron doses per month given to prevalent HD patients in DOPPS III. Results are based on a point-prevalent cross-section of Japanese HD patients having ESRD >180 days at the start of DOPPS III; analyses were restricted to patients receiving IV iron during the first month after study entry (n = 1336).

Fig. 4

Iron management and patient haemoglobin levels in DOPPS II and III. (A) Percentage of facility patients receiving IV iron and the mean haemoglobin concentration in Japanese HD patients having ESRD >180 days. The association between facility IV iron use and patient Hb levels was estimated using mixed linear regression models adjusted for age, sex, years with ESRD, coronary artery disease, congestive heart failure, other cardiovascular disease, cerebrovascular disease, peripheral vascular disease, hypertension, recurrent cellulitis/gangrene, diabetes, lung disease, GI bleed in prior year, neurologic disease, psychiatric disorder, cancer, HIV and albumin. Facility IV iron use was calculated as the percentage of IV iron use in a cross-section of facility HD patients having ESRD >180 days in DOPPS II and III (n = 2850). (B) Difference in the mean haemoglobin concentration among patients by levels of ferritin (n = 3244) and percent transferrin saturation (TSAT) (n = 2850). The relationship was estimated using mixed linear regression models with the patient haemoglobin level as the outcome, adjusting for the same factors as in (A), as well as calcium, phosphorus and BMI. Results are based on a prevalent cross-section of DOPPS II and III HD patients having ESRD >180 days at the time of study initiation.

Fig. 5

Baseline patient haemoglobin levels and subsequent mortality risk. Cox regression models were used to estimate the relationship between the mortality risk and levels of patient Hb either as a continuous variable (inset) or as categories of Hb. Results are based upon data combined from DOPPS phases I, II and III for patients having ESRD >180 days, and were adjusted for age, sex, BMI, years with ESRD, coronary artery disease, congestive heart failure, other cardiovascular disease, cerebrovascular disease, peripheral vascular disease, hypertension, recurrent cellulitis/gangrene, diabetes, lung disease, GI bleed in prior year, neurologic disease, psychiatric disorder, cancer, HIV, single-pool Kt/V, phosphorus, calcium, albumin, study phase and facility clustering effects (n = 5398). Mean study follow-up time was 1.53 years. When limiting the analysis to Hb ≥8 g/dl, the RR was smaller [RR = 0.94 per g/dl higher Hb, P = 0.20 (n = 5091)].

Fig. 6

Time trend in Epo use and mean haemoglobin concentration for new ESRD patients after initiating haemodialysis. The percentage of patients receiving Epo and the mean haemoglobin concentration were determined at 6 points during the first year of haemodialysis for a cohort of new ESRD patients entering DOPPS II within 10 days of their first-ever dialysis treatment. The 6 time points for this analysis were 0–0.3 months, 1.5–3 months, 3.1–5 months, 5.1–7 months, 7.1–9 months and 9.1–12 months (n = 205). Hb (g/dl) = solid line, Epo use = dashed line.