**3. Results**

The distribution of ESA applications in the three observed dialysis centers can be seen in table 1. Totally 185 of 233 patients received at least one ESA dosage. The mean value of ferritin was 538 mg/L. The transferrin saturation (TSAT) did not differ significantly in the observed dialysis units.


Table 1. Application of ESA per dialysis unit and overall.

The mean weekly ESA dosage can be seen in table 2:


Table 2. Mean weekly ESA dosage

162 Progress in Hemodialysis – From Emergent Biotechnology to Clinical Practice

233 chronic hemodialysis patients were included in this clinical evaluation (dialysis center 1 (D1) n= 94, D2 n= 35, D3 n= 104 patients). 54.9% were male; the mean age was 63.8 years (range 22 - 89). The patients in all three centers were comparable with regard to gender distribution, mean age, mean time on dialysis, and distribution of underlying kidney disease. The clinical evaluation was carried out for 12 months retrospectively. Laborchemical parameters were estimated for hemoglobin (Hb) every 2 weeks (labanalyzer), CRP (turbidometry), albumin (alb; nephelometry) and ferritin (chemiluminescence technique) every three months. Serum iron (photometry) and transferrin (turbidometry) were necessary to calculate the transferrin saturation (every 4 weeks). Single pool kt/V was evaluated every 3 months with the Daugirdas technique (Daugirdas, 1993). Intraindividual variability of hemoglobin (Hbvar) was defined as the difference between minimal and maximal concentration (range) and by time to reach the target between Hb 6.8 mmol/l and 8.0 mmol/l within 9 months. Relevant changes in ESA dosages were defined as an elevation greater than two fold and lowering of a half of the

ESA dosage, the end of ESA application or the start with more than 4200 U/week.

Hemodialysis (HD) was performed by MTS 5008 (Fresenius Medical Care), low flux dialyser FX8, FX10 (helixone, Fresenius Medical Care), QB 300 ml/min, QD 500 ml/min, ultrapure dialysis fluid, online hemodiafiltration (olHDF) by MTS 5008 (Fresenius Medical Care; automatic procedure with factor 1.2), high flux dialyser FX 60, FX80 (helixone, Fresenius Medical Care), QB 300 ml/min, QD 350…..360 ml/min, QS 51….60 ml/min, ultrapure dialysis fluid and Nikkiso DBB 05 (Nikkiso Medical Ltd.), high flux dialyser FDY 15 G (PEPA, Nikkiso Medical Ltd.), QB 300 ml/min, QD 700 ml/min, QS 60 ml/min, ultrapure dialysis fluid (QB… blood flow; QD…dialysate flow; Qs…substitution flow). The group "mixed" contained patients started with HD and switched to olHDF (at least 6 months olHDF). We compared the mean values of collected serum parameters three times a month. Descriptive statistical evaluation was calculated by mean, standard deviation and significance by Wilcoxon test, correlation by Spearman rang correlation. The level of

The distribution of ESA applications in the three observed dialysis centers can be seen in table 1. Totally 185 of 233 patients received at least one ESA dosage. The mean value of ferritin was 538 mg/L. The transferrin saturation (TSAT) did not differ significantly in the

> **Application of ESA** <sup>37</sup> 39.4 <sup>4</sup> 11.4 <sup>7</sup> 6.7 <sup>48</sup> **20.6 without ESA At least 1 ESA dosage** 57 60.6 31 88.6 97 93.3 185 **79.4**

Table 1. Application of ESA per dialysis unit and overall.

The mean weekly ESA dosage can be seen in table 2:

**Dialysis unit Total 1 2 3 N % N % N % N %** 

**2. Materials and methods** 

significance was defined as p< 0.05.

**3. Results** 

observed dialysis units.

In nearly all patients (98.9%) an adjustment of ESA dosage was essential. Relevant changes in ESA dosages were defined as an elevation greater than two fold and lowering of a half of the ESA dosage, the end of ESA application or the start with more than 4200 U/week.

The mean value of Hb (measured per patient over the whole study time) was 7.35 mmol/l (Table 3). In patients without ESA application during the 12 months study the mean value of Hb was larger (7.66 mmol/l) in comparison to patients with ESA dosage (7.27 mmol/l).


Table 3. Mean Hb concentrations

Influence of Online Hemodiafiltration on Hemoglobin Level,

Table 6. Relationship between treatment mode and Hb value

**the Hb-value** 

**the Hb-value** 

**HD Mean treatment efficacy (spkt/V) N** 

Table 8. Single Pool Kt/V as a function of the treatment mode

0.66±0.28 mmol/l vs olHDF 0.53±0.16 mmol/l, p<= 0.05): Table 7.

**Intra-individual standard deviation of** 

**Intra-individual standard deviation of** 

**Treatment mode** 

**HD** 

**All patients** 

**All patients** 

**HDF** 

mode

ESA-Dosage and Serum Albumin – A Retrospective, Multicenter Analysis 165

**HD Mean Hb [mmol/L] N** 40 32 74 146

**HDF Mean Hb [mmol/L] N** 15 . 4 19

**Mixed Mean Hb [mmol/L] N** 39 3 26 68

**Total Mean Hb [mmol/L] N** 94 35 104 233

In the olHDF group the intraindividual Hbvar was significantly lower than in HD (HD

Table 7. Intra-individual standard deviation of the Hb-values as a function of the treatment

In the subanalysis the single pool Kt/V (spkt/V) was >1.2 on average in all centers. But there is a significant improvement of spKt/V for olHDF compared to HD (p = 0.04): Table 8:

**HDF Mean treatment efficacy (spkt/V) N** 15 . 4 19

**Mixed Mean treatment efficacy (spkt/V) N** 38 3 26 67

**Dialysis unit** 

**Mean** 7.37 7.16 7.23 **7.25 SD** 0.43 0.59 0.53 0.52

**Mean** 7.58 . 7.50 **7.56 SD** 0.38 . 0.25 0.35

**Mean** 7.56 7.22 7.41 **7.49 SD** 0.46 0.11 0.61 0.52

**Mean** 7.48 7.17 7.29 **7.35 SD** 0.44 0.57 0.55 0.52

**Dialysis unit** 

**N** 40 32 74 146 **Mean** 0.69 0.51 0.71 **0.66 SD** 0.29 0.24 0.26 0.28

**N** 15 . 4 19 **Mean** 0.52 . 0.57 **0.53 SD** 0.11 . 0.30 0.16

**Dialysis unit** 

**1 2 3** 

**Mean** 1.46 1.32 1.55 **1.48 SD** 0.60 0.29 0.38 0.44

**Mean** 1.57 . 1.82 **1.62 SD** 0.17 . 0.52 0.28

**Mean** 1.48 1.16 1.45 **1.45 SD** 0.24 0.04 0.31 0.27

**Total** 

**1 2 3 Total** 

**1 2 3 Total** 


Table 4 shows the intra-individual variability of hemoglobin (Hbvar):

Table 4. Means of haemoglobin variability

The relation between the treatment mode (HD, olHDF) and ESA dosage as well as Hb is shown in the tables 5 and 6:


Table 5. Relationship between treatment mode and required weekly ESA dosage

Hb was larger in the olHDF group and the required ESA dosage to reach the Hb concentration lower (Hb olHDF 7.56± 0.35 mmol/l, HD 7.25± 0.52 mmol/l, p= 0.01; ESA/week olHDF 4407± 4660 U/l, HD 6809±7293 U/l, p= 0.1): Table 6.

**ESA** <sup>37</sup> 4 7 48 **without ESA Hb range (min-max) N** 

**at least one ESA dosage Hb range (min-max) N** 57 31 97 185

**Total Hb range (min-max) N** 94 35 104 233

The relation between the treatment mode (HD, olHDF) and ESA dosage as well as Hb is

**HD All patients N** 40 32 74 146

**HDF All patients N** 15 . 4 19

**Mixed All patients N** 39 3 26 68

Hb was larger in the olHDF group and the required ESA dosage to reach the Hb concentration lower (Hb olHDF 7.56± 0.35 mmol/l, HD 7.25± 0.52 mmol/l, p= 0.01;

Table 5. Relationship between treatment mode and required weekly ESA dosage

ESA/week olHDF 4407± 4660 U/l, HD 6809±7293 U/l, p= 0.1): Table 6.

**Patients with at least one ESA dosage N** 22 28 69 119

**Patients with at least one ESA dosage N** 9 . 4 13

**Patients with at least one ESA dosage N** 26 3 24 53

**Dialysis unit** 

**Mean** 1.98 1.35 1.93 **1.92 SD** 0.92 0.68 1.11 0.93

**Mean** 2.20 1.74 2.41 **2.23 SD** 0.73 0.85 0.88 0.86

**Mean** 2.11 1.70 2.37 **2.17 SD** 0.81 0.83 0.90 0.88

**Dialysis unit** 

**Mean** 3608 6132 8833 **6809 SD** 5058 5511 8313 7293

**Mean** 6560 7009 9473 **8354 SD** 5217 5339 8248 7234

**Mean** 3515 . 7750 **4407 SD** 4160 . 5535 4660

**Mean** 5859 . 7750 **6441 SD** 3853 . 5535 4287

**Mean** 3505 3821 10378 **6147 SD** 3960 1500 9441 7313

**Mean** 5257 3821 11243 **7887 SD** 3775 1500 9314 7410

**1 2 3 Total** 

**1 2 3 Total** 

Table 4 shows the intra-individual variability of hemoglobin (Hbvar):

Table 4. Means of haemoglobin variability

shown in the tables 5 and 6:


Table 6. Relationship between treatment mode and Hb value

In the olHDF group the intraindividual Hbvar was significantly lower than in HD (HD 0.66±0.28 mmol/l vs olHDF 0.53±0.16 mmol/l, p<= 0.05): Table 7.


Table 7. Intra-individual standard deviation of the Hb-values as a function of the treatment mode

In the subanalysis the single pool Kt/V (spkt/V) was >1.2 on average in all centers. But there is a significant improvement of spKt/V for olHDF compared to HD (p = 0.04): Table 8:


Table 8. Single Pool Kt/V as a function of the treatment mode

Influence of Online Hemodiafiltration on Hemoglobin Level,

 **[g/l]** 

**HDF albumin [g/l]** 

**Mixed albumin [g/l]** 

Table 12. Relationship between albumin levels and treatment mode

 **[mg/l]** 

**[mg/l]** 

 **[mg/l]** 

Table 13. Relationship between CRP levels and treatment mode

dosage and Hbvar were reduced in comparison to the other centers.

**Mode** 

**Mode** 

**4. Discussion** 

reduced ESA needs.

**HDF CRP** 

**Mixed CRP** 

ESA-Dosage and Serum Albumin – A Retrospective, Multicenter Analysis 167

**HD albumin** 40 32 74 146

**HD CRP** 39 30 71 140

Our retrospective analysis was performed in three different dialysis centers for 12 months. The D1 center had the largest percentage of patients treated with olHDF (olHDF+"mixed") (57 % in D1 vs. 9 % in D2, 29 % in D3). In D1 the lowest dosage of ESA to reach the Hb target was used (Table 2; D1 vs D2 p= 0.003; D1 vs D3 p< 0.0001), the smallest number of D1 patients were treated with ESA and the time in target was longer than in D2 and D3. In addition, it could be demonstrated that in D1 patients the frequency of adaptation of ESA

Concerning the ferritin values and the transferrrin saturation (TSAT) there were no noticeable differences between the observed centers. But the subanalysis shows a positive correlation of the overall TSAT values with the Hb values (p = 0.002, see Table 11) and a negative one with the mean ESA consumption (p = 0.05). These results comply with the expectation because an improved Hb value is connected with a larger TSAT level and

The treatment efficacy (single pool and equilibrated Kt/V; spKt/V, eKt/V), which was measured periodically in the 3 dialysis units, did not show any significant influence on ESA

**N** 

**N** 

**Dialysis unit** 

**Mean** 39.89 39.35 38.58 **39.11 SD** 3.10 2.11 2.72 2.76

**N** 14 . 4 18 **Mean** 40.74 . 40.24 **40.63 SD** 2.32 . 2.17 2.23

**N** 39 3 26 68 **Mean** 40.51 40.35 39.24 **40.02 SD** 3.35 3.06 3.21 3.30

**Dialysis unit** 

**Mean** 18.56 15.52 14.94 **16.07 SD** 26.70 8.82 10.05 16.26

**N** 12 . 2 14 **Mean** 10.81 . 4.81 **9.96 SD** 8.68 . 0.22 8.28

**N** 36 3 25 64 **Mean** 14.52 7.36 10.43 **12.59 SD** 10.79 2.55 7.81 9.66

**1 2 3 Total**

**1 2 3 Total**

Further analyses regarded the relationship between CRP and albumin. The tables 9 and 10 show the mean levels of CRP and albumin:


Table 9. Mean CRP level per dialysis unit and overall


Table 10. Mean albumin level per dialysis unit and overall

For all patients the Hb level was negatively correlated to CRP (r= - 0.24, p< 0.0005) and positively to Albumin (r= 0.30, p< 0.0001) and TSAT (r= 0.20, p< 0.005): see table 11:


Table 11. Correlation of the total values for CRP, Albumin and TSAT with Hemoglobin

In a subanalysis we found significantly larger albumin levels and lower CRP concentrations in olHDF vs HD (albumin olHDF 40.63+/-2.23 g/l, HD 39.11± 2.76 g/l, p< 0.05; CRP olHDF 9.96± 8.28 mg/l, HD 16.07 ± 16.26 mg/l, p< 0.05): Tables 12 and 13:


Table 12. Relationship between albumin levels and treatment mode


Table 13. Relationship between CRP levels and treatment mode
