**4. Discussion**

166 Progress in Hemodialysis – From Emergent Biotechnology to Clinical Practice

Further analyses regarded the relationship between CRP and albumin. The tables 9 and 10

**Mean CRP [mg/l] N** 87 33 98 218

**Mean albumin [g/l] N** 93 35 104 232

For all patients the Hb level was negatively correlated to CRP (r= - 0.24, p< 0.0005) and

**Spearman Correlation Coefficients Prob > |r| under H0: Rho=0 Number of Observations** 

positively to Albumin (r= 0.30, p< 0.0001) and TSAT (r= 0.20, p< 0.005): see table 11:

**Dialysis units** 

**Dialysis unit** 

**Mean** 40.28 39.44 38.81 **39.49 SD** 3.10 2.17 2.84 2.93 **Min** 30.4 35.8 31.0 30.4 **Median** 40.5 39.6 39.0 39.6 **Max** 47.1 43.7 45.9 47.1

**esamean hbmean** 


0.30050 <.0001 232

0.19808 0.0024 233

0.08497 0.2115 218



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

9.96± 8.28 mg/l, HD 16.07 ± 16.26 mg/l, p< 0.05): Tables 12 and 13:

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

**1 2 3 Total**

**Mean** 15.82 14.77 13.58 **14.65 SD** 19.48 8.75 9.67 14.30 **Min** 3.6 4.5 3.1 3.1 **Median** 10.2 13.1 10.4 10.6 **Max** 160 47.6 40.5 160

**1 2 3 Total**

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

**crpmean**  CRP

**albmean**  Albumin

**tsatmean**  TSAT

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

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 reduced ESA needs.

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

Influence of Online Hemodiafiltration on Hemoglobin Level,

Fig. 2. Mean serum albumin concentration HD vs. olHDF (p=0.01)

from HD to olHDF) showed an increase in albumin level rather than a decrease.

**g/l**

Fig. 3, and Table 13:

Fig. 3. Mean CRP concentration HD vs. olHDF (p=0.02)

**mg/l**

ESA-Dosage and Serum Albumin – A Retrospective, Multicenter Analysis 169

**Mean Albumin HD vs olHDF**

HD olHDF Mixed **Procedures**

Albumin losses during renal replacement procedures are generally thought of being unwanted, as low serum albumin correlates with poor outcome in dialysis patients. Therefore, olHDF, that technically spoken is an albumin-loosing therapy, might carry the danger of exposing the treated patients to threads associated with low albumin levels. It is striking that in our analysis the olHDF group had the largest serum albumin concentration (Fig. 2, Table 12). All patients of the "mixed" group (containing patients that had switched

Moreover, olHDF can remove proinflammatory substances such as cytokines (Bellomo et al., 1991; Lee et al., 2004). Again, we could confirm this phenomenon with lower CRP levels in the olHDF group vs. HD group (9.96+/- 8.28 mgl/l vs. HD 16.07+/- 16.26 mg/l, p=0.02), see

**Mean CRP Levels HD vs olHDF**

HD olHDF Mixed **Procedures**

dosage and Hb levels. But the subanalysis calculating the impact of the different treatment modes on Kt/V resulted in a significant increased spKt/V for olHDF treatments compared with HD (1.62±0.28 for olHDF versus 1.48±0.44 for HD; Table 8).

Interestingly the correlation analysis also shows a highly significant positive correlation of the mean albumin level with the mean Hb values (p < 0.001, Table 11) and a negative one with the mean ESA dosage (p = 0.0003). Simultaneously CRP is negatively correlated with Hb (p = 0.0004, Table 11).

The significant difference in albumin concentration most likely played the decisive role for ESA dosage and Hb level (Ward, 2005). It is known that in patients who underwent convective-diffusive treatment the ESA dosage could be reduced (Vaslaki et al., 2006; Bonforte et al., 2002; Eiselt et al., 2000). That observation was confirmed by our results, reaching an economically interesting level of savings in ESA costs: Fig. 1.

Fig. 1. Mean Hb level and ESA dosage HD vs. HDF (ESA: p=0.1, ns., Hb: p=0.01)

Typically, convective diffusive procedures are characterized by an additional removal of hydrophobic middle molecules and protein (albumin) bound uremic toxins depending on the membrane characteristics (hydrophobic areas, pore size, adsorptive properties, biocompatibility) (Ahrenholz et al., 2004; Panicchi et al., 2008). The loss of protein bound substances leads to a membrane determined loss of albumin during olHDF sessions (Ahrenholz et al., 2004; Samtleben et al., 2003; Combarnous et al., 2002). In low flux dialysis protein removal only occurs with adsorptive membranes (PMMA, polyacrilonitrile) with decreasing dialysis efficacy for water soluble toxins (Parzer et al., 1993). This removal of albumin can be compensated after a time of about 12 weeks in the absence of relevant inflammation (Ding et al., 2002; Kaysen et al., 1997). In chronic ambulant peritoneal dialysis protein losses are in-between 6 to 10 g/d and albumin losses up to 5 g/d over the peritoneal membrane (Kaysen et al., 1984).

dosage and Hb levels. But the subanalysis calculating the impact of the different treatment modes on Kt/V resulted in a significant increased spKt/V for olHDF treatments compared

Interestingly the correlation analysis also shows a highly significant positive correlation of the mean albumin level with the mean Hb values (p < 0.001, Table 11) and a negative one with the mean ESA dosage (p = 0.0003). Simultaneously CRP is negatively correlated with

The significant difference in albumin concentration most likely played the decisive role for ESA dosage and Hb level (Ward, 2005). It is known that in patients who underwent convective-diffusive treatment the ESA dosage could be reduced (Vaslaki et al., 2006; Bonforte et al., 2002; Eiselt et al., 2000). That observation was confirmed by our results,

**Mean Hb and ESA dosage HD vs. olHDF**

HB

ESAx1000

HD HDF Mixed **Procedures**

Typically, convective diffusive procedures are characterized by an additional removal of hydrophobic middle molecules and protein (albumin) bound uremic toxins depending on the membrane characteristics (hydrophobic areas, pore size, adsorptive properties, biocompatibility) (Ahrenholz et al., 2004; Panicchi et al., 2008). The loss of protein bound substances leads to a membrane determined loss of albumin during olHDF sessions (Ahrenholz et al., 2004; Samtleben et al., 2003; Combarnous et al., 2002). In low flux dialysis protein removal only occurs with adsorptive membranes (PMMA, polyacrilonitrile) with decreasing dialysis efficacy for water soluble toxins (Parzer et al., 1993). This removal of albumin can be compensated after a time of about 12 weeks in the absence of relevant inflammation (Ding et al., 2002; Kaysen et al., 1997). In chronic ambulant peritoneal dialysis protein losses are in-between 6 to 10 g/d and albumin losses up to 5 g/d over the peritoneal

Fig. 1. Mean Hb level and ESA dosage HD vs. HDF (ESA: p=0.1, ns., Hb: p=0.01)

with HD (1.62±0.28 for olHDF versus 1.48±0.44 for HD; Table 8).

reaching an economically interesting level of savings in ESA costs: Fig. 1.

Hb (p = 0.0004, Table 11).

3,5 5,5 7,5 9,5 11,5 13,5

membrane (Kaysen et al., 1984).

**mmol/l- ESAx1000 U/l**

Fig. 2. Mean serum albumin concentration HD vs. olHDF (p=0.01)

Albumin losses during renal replacement procedures are generally thought of being unwanted, as low serum albumin correlates with poor outcome in dialysis patients. Therefore, olHDF, that technically spoken is an albumin-loosing therapy, might carry the danger of exposing the treated patients to threads associated with low albumin levels.

It is striking that in our analysis the olHDF group had the largest serum albumin concentration (Fig. 2, Table 12). All patients of the "mixed" group (containing patients that had switched from HD to olHDF) showed an increase in albumin level rather than a decrease.

Moreover, olHDF can remove proinflammatory substances such as cytokines (Bellomo et al., 1991; Lee et al., 2004). Again, we could confirm this phenomenon with lower CRP levels in the olHDF group vs. HD group (9.96+/- 8.28 mgl/l vs. HD 16.07+/- 16.26 mg/l, p=0.02), see Fig. 3, and Table 13:

Fig. 3. Mean CRP concentration HD vs. olHDF (p=0.02)

Influence of Online Hemodiafiltration on Hemoglobin Level,

*Nephrol* . Vol 18: 2219- 2220

2315- 2321

ESA-Dosage and Serum Albumin – A Retrospective, Multicenter Analysis 171

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Because albumin is a negative acute phase protein we can, in general, expect higher concentrations at lower inflammation (Panicchi et al., 2006; Kaysen et al., 1997). However, none-biocompatible membranes and partly low flux hemodialysis increases proinflammatory cytokines such as TNF-alpha. Ultrapure dialysis fluid is of relevant importance to prevent inflammation (Panicchi et al., 2008). On the other hand complement activation plays a role for inflammation during the dialysis sessions therefore biocompatible membranes are urgently necessary (Hakim et al., 1984). In the olHDF method as use in this study, both ultrapure dialysate and biocompatible membrane materials were used, enabling clear attenuation of procedure-associated inflammatory processes. This attenuation of inflammation to us seems the key factor for increased albumin production that even makes up for procedure-associated albumin losses. The nutritional situation (nPCR) has only a secondary influence (Savica et al., 2006; Stenvinkel, 2005). Hbvar also depends on inflammation and albumin concentration (Brimble et al., 2007). Hbvar in olHDF is lower than in HD because of less inflammation and higher concentration of albumin.
