Sodium removal during pre-dilution haemofiltration

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1 Nephrol Dial Transplant (2003) 18 [Suppl 7]: vii31 vii36 DOI: /ndt/gfg1076 Sodium removal during pre-dilution haemofiltration Salvatore Di Filippo, Celestina Manzoni, Simeone Andrulli, Francesca Tentori and Francesco Locatelli Department of Nephrology and Dialysis, A. Manzoni Hospital, Lecco, Italy Abstract Background. Cardiovascular instability still affects a large percentage of uraemic patients undergoing extracorporeal substitutive treatments. Post-dilution haemofiltration has been reported to be a method for improving cardiovascular stability; however, the limited removal of small molecular weight solutes together with the need for high blood flow from the fistula greatly restrict the use of this treatment. To increase the solute clearances and to partially resolve the necessity for high blood flow, the replacement solution, in a quantity about double that used in postdilution mode, can be administered in pre-dilution mode. A high vascular stability has also been observed for pre-dilution haemofiltration. Since the lower morbidity may be due to less sodium removal when compared with haemodialysis, it would be important to characterize the sodium transport in this kind of treatment. Methods. Nine patients underwent nine pre-dilution haemofiltration treatments (one for each patient) with on-line prepared substitution fluid. Results. As mean values, total (NaF pw ) and ionized (NaE pw ) plasma water sodium concentrations increased from ± 2.8 meq/l to ± 2.4 meq/l, and from ± 2.8 to ± 1.2 meq/l, respectively, during the treatment, suggesting a hypotonic concentration of net ultrafiltrate. Plotting the difference between final and initial ionized plasma water concentrations (fnae pw inae pw ) against the difference between initial plasma water values and ionized sodium concentration in the reinfusate (inae pw NaE R ), a significant negative correlation was found, with the regression line that intercepts the abscissa at the (inae pw NaE R ) value of 8.8 meq/l; this means that to avoid changes in NaE pw in our patients, the NaE R should be lower than the inae pw by this amount. This Correspondence and offprint requests to: Dr Salvatore Di Filippo MD, Divisione di Nefrologia e Dialisi, Azienda Ospedale A. Manzoni, Via Dell Eremo 9 11, Lecco, Italy. s.difilippo@ospedale.lecco.it is quite different from the theoretical value of 4 meq/l necessary to avoid changes in NaE pw during haemodialysis. The ratio between the total sodium concentration in the ultrafiltrate (NaF uf ) and NaF pw () at the post-reinfusion site was 0.96 and decreased to 0.94 when NaF pw values at the pre-reinfusion site were considered. This last value is quite close to the theoretical value of post-dilution haemofiltration. Conclusion. As for post-dilution haemofiltration, less sodium removal, compared with haemodialysis, can partly explain the improved cardiovascular stability during pre-dilution haemofiltration. Keywords: cardiovascular stability; direct ionometry; flame photometry; haemofiltration; sodium flux Introduction Despite technological advances, cardiovascular instability still affects a large percentage of uraemic patients undergoing extracorporeal substitutive treatments. While its pathogenesis is multifactorial, older age and increased co-morbidity at the start of substitutive therapy play a major role. Considering these epidemiological characteristics, emphasis has to be placed on possible means of improving the cardiovascular stability. Dialysate sodium concentration is one of the main factors affecting intradialytic cardiovascular stability, and has been progressively increased [1,2]. However, while effective in reducing intradialytic morbidity (hypotension and muscle cramps), the systematic use of higher sodium concentrations has some disadvantages (hypertension and pulmonary oedema), particularly as sodium balance is checked infrequently. Post-dilution haemofiltration has been reported to be an alternative method to improve cardiovascular stability, possibily because of different effects on peripheral resistance [3,4]. However, the lower morbidity rates reported for post-dilution haemofiltration ß 2003 European Renal Association European Dialysis and Transplant Association

2 vii32 may be partially due to the lower sodium removal [5], and the potential side effects mentioned above may persist. Furthermore, the limited removal of small molecular weight solutes and the need for high blood flow from the vascular access greatly limit the use of this technique. To increase the solute clearances and to partially resolve the necessity for high blood flow, the replacement solution, in a quantity about double that used in post-dilution mode, can be administered in predilution mode [6]. High vascular stability has also been observed with this mode of haemofiltration (predilution haemofiltration) [7]. Since less morbidity may be related to less sodium removal compared with haemodialysis, it would be important to characterize the sodium transport also for this kind of treatment. Sodium flux Sodium crosses dialysis membrane by means of two mechanisms: convection and diffusion. Convection. Both ionized sodium and sodium complexed with non-protein anions follow water during convective transport. The sodium concentration has been shown to be lower in the ultrafiltrate compared with plasma water undergoing ultrafiltration [5,8], and both total and ionized plasma water sodium concentrations increase during isolated ultrafiltration [9]. This is due to the so-called Donnan effect which is related to the negatively charged plasma proteins incapable of crossing the dialysis membrane [10]. In order to obtain the value of ultrafiltrable sodium, total plasma sodium concentration, measured by flame photometry (NaF pl ), must be corrected in total plasma water sodium concentration (NaF pw ), and the correction can be made using the formula proposed by Waugh [11]: NaF pw ¼ NaF pl 100=ð99:1 1:03 T:L 0:73 T:PÞ ð1þ where T.L is the total plasma lipid concentration (g/dl) and T.P is the total plasma protein concentration (g/dl). The NaF pw value is then corrected for the factor, which can be defined as: ¼ NaF uf =NaF pwðiþ where NaF uf is ultrafiltrate total sodium concentration measured by flame photometry and NaF pw(i) is total sodium concentration in the aqueous phase of the inlet plasma stream. Values of have been measured as a function of the mean plasma total protein concentration (m-t.p) across the dialyser, and the general dependence of on m-t.p has been found to be [12]: ¼ð1:000±0:02Þ 0:0073 m-t:p ð2þ S. Di Filippo et al. Hence, under typical haemodialysis conditions with a mean total protein concentration across the dialyser of 7.5 g/dl, the value averages In pre-dilution haemofiltration, the mean protein concentration across the haemofilter is usually lower than in haemodialysis, and with similar blood and reinfusate flows, a mean total protein concentration across the haemofilter of 5 g/dl and an value of 0.96 can be predicted. Diffusion. Sodium flux across the dialysis membrane by diffusion is a function of sodium activity in plasma water and dialysate streams. If total sodium content is correctly measured by flame ionometry, ionized sodium concentrations are correctly determined by means of direct ionometry [13]. In order to calculate the value of diffusible sodium, plasma water ionized sodium concentration (NaE pw ) has to be corrected for a Donnan factor of 0.97 that is the ratio between ionized sodium concentration in the dialysate (NaE D ) and NaE pw at equilibrium. Thus, when NaE D corresponds to NaE pw multiplied by 0.97, there is no diffusive sodium flux [14]. The relationship between total sodium concentrations measured by flame photometry and ionized sodium concentrations measured by direct ionometry was investigated in vivo (Figure 1). In plasma, at physiological total protein concentration, the following relationship has been reported: NaE/NaF ¼ If NaF pl equals 140 meq/l, NaE pw will be 142 meq/l. Considering an average serum total lipid and total protein of 0.6 and 7.0 g/dl, respectively, applying Waugh s formula, NaF pw will be 150 meq/l, and for an value of 0.95, NaF uf will be 142 meq/l. This value is very close to that obtained on the same plasma sample by ionometry, so for clinical purposes it seems acceptable to assume NaF uf to be equivalent to NaE pw in haemodialysis. At the base concentrations currently used, the following relationship has been reported in the dialysate: NaE/NaF ¼ This means that for NaF D of 140 meq/l, NaE D will result in a value of 4 meq/l lower [15]. Sodium flux during haemodialysis Equation 3 illustrates the expression to calculate sodium removal rate during haemodialysis (JNa HD ): JNa HD ¼ D ðnae pwi 0:97 NaE Di ÞþUF ½NaE pwi D=Qe i ðnae pwi 0:97 NaE Di ÞŠ where D is sodium dialysance, UF is the ultrafiltration rate, 0.97 is the Donnan factor, Qe i is the inlet blood water flow and NaE Di and NaE pwi are ionized sodium concentrations in the inlet dialysate and plasma water streams. The first term of the equation accounts for the diffusive component of sodium flux, whereas the second term shows the convective component. ð3þ

3 Sodium and haemofiltration 150 vii33 meq/l NaF NaE NaF-pw 120 Blood Ultrafiltrate Dialysate Fig. 1. Relationships between total (NaF) and ionized (NaE) sodium concentrations in blood, ultrafiltrate and dialysate. Plasma water total sodium concentrations are calculated according to Waugh s formula and considering total lipid and total protein concentration of plasma close to 0.6 and 7.0 g/dl. Adapted from [15]. 250 JNa/UF HD pre-hf NaEpw NaFpw Fig. 2. Theoretical total sodium concentration in net ultrafiltrate (JNa/UF) during haemodialysis (HD) and pre-dilution haemofiltration (pre-hf) at different ionized (NaE pw ) and total (NaF pw ) plasma water sodium concentrations and identical dialysate (NaF Di ) and reinfusate (NaF R ) total sodium concentrations. meq/l Assuming D ¼ 0.18 l/min, NaE Di ¼ 136 meq/l for NaF Di ¼ 140 meq/l, UF ¼ 0.02 l/min and Qe i ¼ 0.3 l/min, the result for JNa HD will be: 2.21 meq/min for NaE pwi of 137 meq/l, 3.13 meq/min for NaE pwi of 142 meq/l and 4.05 meq/min for NaE pwi of 147 meq/l. When the sodium flux (JNa) is divided by UF, the Na concentration in the ultrafiltrate, resulting from the combined diffusive and convective transport mechanisms, will be 111, 157 and 202 meq/l, respectively. Sodium flux during pre-dilution haemofiltration Equation 4 calculates the sodium removal rate during pre-dilution haemofiltration (JNa HF ): JNa HF ¼ ½ðQe i NaF pwi þ Q R NaF R Þ= ðqe i þ Q R ÞŠ ðq R þ UFÞ ðq R NaF R Þ where Q R is the rate of reinfusate and NaF R is the total sodium concentration in the reinfusate fluid. Assuming as typical haemofiltration conditions, Qe i and Q R ¼ 0.3 l/min, ¼ 0.96 and NaF R ¼ 140 meq/l and equal to NaF Di. For NaE pwi values of 137, 142 and 147 meq/l and according to the relationship shown in ð4þ Figure 1, NaF pwi values of 145, 150 and 155 meq/l, respectively, can be calculated. For UF values similar to haemodialysis and according to Equation 4, sodium removal will result in 1.78 for NaE pwi of 137 meq/l, 2.54 for NaE pwi of 142 meq/l and 3.31 meq/min for NaE pwi of 147 meq/l. When sodium flux is divided by UF, the sodium concentration in the ultrafiltrate will be 89, 127 and 166 meq/l, respectively. These values are lower than the respective values calculated for haemodialysis (Figure 2), and predicting, for similar total sodium concentrations in the dialysate and in the reinfusate, less sodium removal during pre-dilution haemofiltration. Pre-dilution haemofiltration. In vivo data Nine patients underwent nine pre-dilution haemofiltration treatments with on-line prepared substitution fluid. Mean Qe i was 0.29 ± 0.02 l/min; mean Q R ¼ 0.34 ± 0.03 l/min; mean NaF R ¼ ± 1.8 meq/l; mean NaE R ¼ ± 1.3 meq/l. Patients sodium concentrations were determined at the beginning

4 vii34 (ina pw ) and at the end of each session (fna pw ), as well as during the session (15 min after start and 15 min before the end of the treatment). Intra-treatment blood samples were collected before the haemofilter at two different sites: pre-reinfusion (pre-r) and postreinfusion (post-r) sites, and in the venous line (V). Intra-treatment blood samples and ultrafiltrate samples were collected. Sodium concentrations were measured in duplicate by flame photometry and by direct ionometry. Correction for plasma water total sodium concentration was made using Equation 1 and assuming a total lipid concentration equal to 0.6 g/dl for all patients. Results Both mean NaF pw and NaE pw increased during treatment, suggesting a hypotonic concentration of net ultrafiltrate. The mean NaF pw changed from ± 2.8 meq/l to ± 2.4 meq/l and the mean NaE pw from ± 2.8 meq/l to ± 1.2 meq/l. S. Di Filippo et al. Figure 3 shows the relationship between the difference (fnae pw inae pw ) and the difference (inae pw NaE R ). A significant negative correlation was found, with the regression line intercepting the abscissa at the (inae pw NaE R ) value of 8.8 meq/l. This means that to avoid changes in NaE pw in our patients, the NaE R should be lower than the inae pw by this amount. This is quite different from the theoretical value of 4 meq/l necessary to avoid changes in NaE pw during haemodialysis. The projected regression line intercepts the ordinate at a (fnae pw inae pw ) value of 6.6 meq/l; therefore, NaE pw would increase by this amount when using reinfusate with the same ionized sodium concentration as that of plasma water. Figure 4 shows the data on the intra-treatment sodium concentrations. Secondary to the hypotonic concentration of the reinfusate, both post-r NaF pw and post-r NaE pw resulted in lower values than pre-r values, with a mean post-r/pre-r ratio of ± for NaF pw and ± for NaE pw. Secondary to the hypotonic concentration of the ultrafiltrate, both venous NaF pw and NaE pw values NaEpw (f -i) (inaepw-naer) Fig. 3. Regression plot of the NaE pw (f i) difference against the (inae pw NaE R ) difference. The regression coefficient (r ¼ 0.97) is highly significant (P < 0.001). meq/l Pre-R Post-R V NaFpw NaEpw (T.P. g/dl) Fig. 4. Intra-treatment total (NaF pw ) and ionized (NaE pw ) plasma water sodium concentrations and total plasma protein (T.P) concentration during pre-dilution haemofiltration at three different sites of the extracorporeal circuit: pre-reinfusion site (pre-r); post-reinfusion site (post- R); venous line (V).

5 Sodium and haemofiltration Table 1. Total plasma water and ultrafiltrate sodium concentrations and factors were higher than the post-r values, with a mean venous/post-r ratio of ± for NaF pw and ± for NaE pw. Total plasma water and ultrafiltrate sodium concentrations and NaF uf /post-r NaF pw and NaF uf /pre-r NaF pw ratios ( factor) are shown in Table 1. Mean NaF uf was 96% of the mean plasma water total sodium concentration at the post-r site. This value was very similar to the theoretical value calculated according to the determined mean plasma total protein concentration: m-t.p ¼ 5.6 ± 0.5 g/dl; ¼ ± On the other hand, when pre-r NaF pw values were considered, the NaF uf /pre-r NaF pw ratio was This last value is closer to the theoretical value of post-dilution haemofiltration. In other words, in our patients, we could expect a similar sodium removal with both pre- and post-dilution haemofiltration. Discussion Plasma water pre-r Plasma water post-r On-line preparation of infusion solution has created a renewed interest in haemofiltration. Because reinfusate volume is no longer a limiting factor, haemofiltration can be performed in a pre-dilution mode, which resolves the limitations of blood flow, urea clearance and viscosity. Similarly to post-dilution haemofiltration, improved haemodynamic stability with an increase in vascular resistance [16] and a lower incidence of intradialytic symptoms compared with haemodialysis have been reported for pre-dilution haemofiltration [7,17]. However, the lower morbidity rates reported for postdilution haemofiltration may at least be partially due to the reduced sodium removal compared with haemodialysis [5]. Our calculations demonstrate that in pre-dilution haemofiltration, with a reinfusate sodium concentration equal to dialysate sodium concentration, sodium concentration in the net ultrafiltrate is expected always to be lower than in haemodialysis. This result is partially secondary to the so-called Donnan effect and partially to the dilutional effect on plasma water sodium concentration of reinfusate, with post-r Na pw concentrations being always lower than the pre-r values. Our results show no changes in ionized plasma water sodium concentration for a difference of 8.8 meq/l between NaE pw and NaE R. Because this effect is obtained in haemodialysis with a mean difference between NaE pw and NaE Di of only 4 meq/l, it is UF NaF ± ± ± ± ± vii35 reasonable to expect less sodium removal in predilution haemofiltration when NaE R is equal to NaE Di. In haemodialysis, the single pool variable volume sodium kinetic model allows prediction of fnae pw with a very low level of imprecision when inae pw and NaE Di are known [14]. Applying this model to our patients and assuming NaE Di equal to NaE R, the predicted fnae pw value was 2.9 ± 0.7 meq/l lower than the fnae pw values determined during haemofiltration. Based on these results, and in order to obtain similar end-treatment sodium contents, a dialysate sodium concentration 5.5 ± 0.9 meq/l higher than the reinfusate sodium concentration should have been used. Finally, we calculated that similar end dialysis sodium contents could have been obtained by decreasing net ultrafiltration during haemodialysis from 2.8 ± 1 to 2.2 ± 0.9 l. In other words, switching from haemofiltration to haemodialysis, dry body weight should have been increased by 0.6 kg to yield similar endtreatment sodium contents. This quite high value can explain to a large extent the improved cardiovascular stability in pre-dilution haemofiltration. References 1. Stewart WK, Fleming LW, Manuel MA. Benefits obtained by the use of high sodium dialysate during maintenance hemodialysis. Proc Eur Dial Transplant Assoc 1972; 9: Locatelli F, Pedrini L, Ponti R et al. Physiological and pharmacological dialysate sodium concentrations. Int J Artif Organs 1982; 5: Shaldon S, Deschodt G, Beau MC, Claret G, Mion H, Mion C. Vascular stability during high flux hemofiltration (HF). Proc Eur Dial Transplant Assoc 1979; 16: Baldamus CA Ernst W, Fassbinder W, Koch KM. Differing haemodynamic stability due to differing sympathetic response: comparision of ultrafiltration, haemodialysis and haemofiltration. Proc Eur Dial Transplant Assoc 1980; 17: Gotch FA, Sargent JA. Hemofiltration: an unnecessarily complex method to achieve hypotonic sodium removal and controlled ultrafiltration. Blood Purif 1983; 1: David S, Bostrom M, Cambi V. Predilution hemofiltration. Clinical experience and removal of small molecular weight solutes. Int J Artif Organs 1995; 18: Altieri P, Sorba G, Bolasco P et al. Pre-dilution haemofiltration the Second Sardinian Multicentre Study: comparision between haemofiltration and haemodialysis during identical Kt/V and session times in a long-term cross-over study. Nephrol Dial Transplant 2001; 16: Locatelli F, Ponti R, Pedrini L, Costanzo R, Di Filippo S, Marai P. Sodium kinetics across dialysis membranes. Nephron 1984; 38: Nolph KD, Stoltz ML, Carter CB, Fox M, Maher JF. Factors affecting the composition of ultrafiltrate from hemodialysis coils. Trans Am Soc Artif Intern Organs 1970; 16: Donnan FG. The theory of membrane equilibria. Chem Rev 1924; 1: Waugh WH. Utility of expressing serum sodium per unit of water in assessing hyponatremia. Metabolism 1969; 18: Gotch FA, Lam MA, Prowitt M, Keen ML. Preliminary clinical results with sodium-volume modeling of hemodialysis therapy. Proc Clin Dial Transplant Forum 1980; 10: Stiller S, Mann H. Ionometry versus flame photometry in dialysis therapy. ESAO Proceedings, Athens, Greece; 1985: 63 69

6 vii Di Filippo S, Corti M, Andrulli S, Manzoni C, Locatelli F. Determining the adequacy of sodium balance in hemodialysis using a kinetic model. Blood Purif 1996; 14: Locatelli F, Ponti R, Pedrini L, Di Filippo S. Sodium kinetics and dialysis performances. Contrib Nephrol 1989; 70: van Kuijk WHM, Hillion D, Savoiu C, Leunissen KML. Critical role of the extracorporeal blood temperature in the hemodynamic S. Di Filippo et al. response during hemofiltration. J Am Soc Nephrol 1997; 8: Altieri P, Sorba GB, Bolasco PG et al. the Sardinian Collaborative Study Group of On-Line Hemofiltration. On-line predilution hemofiltration versus ultrapure high-flux hemodialysis: a multicenter prospective study in 23 patients. Blood Purif 1997; 15:

Acid base homeostasis with the high convective dialysis treatments

Nephrol Dial Transplant (2003) 18 [Suppl 7]: vii26 vii30 DOI: 10.1093/ndt/gfg1075 Acid base homeostasis with the high convective dialysis treatments Mariano Feriani Department of Nephrology and Dialysis,