1 Department of Nephrology, Lapeyronie University Hospital, Montpellier, France, 2 Department of Nephrology, Maisonneuve-Rosemont Hospital, Montréal, Québec and 3 Department of Chemical Engineering, Lakehead University, Thunder Bay, Ontario, Canada
Correspondence and offprint requests to: Prof. Bernard Canaud, Department of Nephrology, Lapeyronie University Hospital, F-34295 Montpellier, France.
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Abstract |
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Methods. This observation was explored in six non-diabetic chronic dialysis patients during 48 HDF sessions using 1.8 m2 polysulphone membrane dialysers. In all six patients, 24 sessions were performed with glucose supplementation (as a continuous D50% (500 g/l) infusion at 40 ml/h) and 24 sessions without supplementation.
Results. Glucose supplementation led to a marked increase in Kuf from 22.8±2.2 (without D50%, n=24) to 32.1±3.9 ml/h/mmHg (with D50%, n=24) (P<0.0001). An increase in percentage reduction ratios for urea and creatinine were also consistently observed during the sessions with glucose administration (from respective mean values of 75±5 and 68±4% to 79±4 and 74±10%). Mean double-pool Kt/V, calculated from serum urea concentrations, rose from 1.65±0.24 (n=24) to 1.86±0.24 (n=24) (P<0.005). Similar results were observed in a subgroup of 18 HDF sessions (nine with glucose and nine without) monitored with an on-line urea sensor of spent dialysate. No detrimental effects were induced at any time.
Conclusions. We conclude that intravenous glucose administration during high-flux HDF using polysulphone membranes increases significantly both ultrafiltration capacity and dialysis dose delivery.
Keywords: haemodiafiltration performances; glucose dialysis dose; membrane permeability
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Introduction |
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In vivo haemodiafilter performances are commonly assessed on two parameters: solute clearances and ultrafiltration coefficient. On one hand, clearances (Kd) permit evaluation of the solute clearing capacity of a haemodiafilter with selected solute marker. Kd gives an indirect insight to the solute membrane permeability. Normalized body clearance known as the `dialysis dose' or Kt/V is one of the most convenient dialysis indices to evaluate objectively the dialysis efficacy. On the other hand, ultrafiltration coefficient (Kuf) permits evaluation of the water plasma filtering capacity of a haemodiafilter. Kuf is a surrogate of haemodiafilter hydraulic permeability that represents the ultrafiltration rate (UFR in ml/h) and transmembrane pressure (TMP in mmHg) ratio. Hydrostatic and osmotic forces both interact to regulate ultrafiltration rate water and transfer across the artificial membrane [4]. In vivo UFR can be altered consequently due to the protein concentrationpolarization effect occurring at the surface of the membrane, particularly with high ultrafiltration rate (100150 ml/min) [57]. Recently, on-line continuous Kuf monitoring has proved useful for real-time assessment of hydraulic permeability changes of the module device during HDF [8]. While evaluating this system in vivo, it was noticed that Kuf changed suddenly during the HDF session with high-flux polysulphone when glucose was infused intravenously to the patient to correct or to prevent hypotensive episodes. This empirical observation prompted us to assess the effects of i.v. glucose administration on high-flux HDF performances and to evaluate its impact on `dialysis dose' delivery.
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Subjects and methods |
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Patients
Six stable haemodialysis dialysis patients were included in this study after informed consent was obtained. The group consisted in four men and two women of a mean age of 41.3±22.4 years. Diabetes mellitus was an exclusion criterion.
Dialysis modality
HDF was performed with 2008E and 4008D volumetric control machines (Fresenius, Bad Homburg, Germany) allowing on-line production of replacement fluid from fresh ultrapure dialysate, as described previously [9]. Dialysate and replacement solutions contained glucose at a concentration of 5.55 mmol/l (1.0 g/l). The blood flow rate was maintained at 350 ml/min and the mean dialysate flow rate was 630±19 ml/min (both were maintained at the same level for a given patient). Session duration was kept constant in each case, varying between 3.0 and 4.0 h. No change in heparin regimen was allowed during the study for the same individual (mean bolus of 2981±1204 IU followed by a maintenance dose of 1773±984 IU/h). HF 80s dialysers (Fresenius, Bad Homburg, Germany), made of 1.8 m2 high-flux polysulphone membrane, were used in all cases. Dialysers were not reused and primed with 2 l of normal saline solution. In each part of the study, nine HDF sessions were monitored with a urea sensor (UM1000, Baxter Healthcare Corporation, McGraw Park, IL, USA) connected on-line to the effluent stream (spent dialysate plus ultrafiltrate).
Recorded parameters and calculations
Kuf was monitored at bedside during the session (DIB08E, Fresenius), as recently described [8]. This data acquisition system allows continuous determination of Kuf throughout the entire session. Kuf is calculated from the ratio of total UFR and TMP measured by the dialysis monitor. In this case, TMP represents the numerical sum of the pressure values recorded in blood and dialysate compartments.
Blood was sampled pre- and immediately post-session for urea, creatinine, glucose, sodium, osmolality, and total protein concentrations, as well as haematocrit determination. In addition, serum glucose concentration was measured simultaneously at the dialyser inlet and outlet, and in the spent dialysate, after 1 h of dialysis. Haematocrit level was also measured from inflow and outflow blood sampling. Pre- and post-session dialysis weight, total and net ultrafiltration, and pre- and post-session mean arterial pressure (MAP) were recorded. Percentage reduction ratio (%) for urea and creatinine and double-pool equivalent Kt/V urea were assessed at each session. Body single-pool Kt/V was calculated according to the equation from Garred et al. [10]:where R,
BW, BW, and tHD represent respectively ratios between pre-and post-dialysis serum urea concentrations, pre- to post-dialysis change in body weight (kg), dry body weight (kg), and session time (h).
Kt/Vsp was then corrected for rebound according to the equation from Daugirdas et al. [11]:The on-line urea sensor (UM1000) on the spent dialysate line provides the solute removal index (SRI) and body Kt/V; both parameters were recorded for the sessions monitored with this device.
Statistics
Results are presented as mean±SD. Where appropriate, paired Student's t-test, and Spearman correlation coefficient were applied for statistical analysis.
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Results |
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Consequences of glucose administration
Instantaneous glucose mass transfer (JGlu, mmol/min) using inlet (Glinlet) and outlet (Gloutlet) dialysate glucose concentrations and dialysate flow (QD) were measured 60 min after the start of HDF session as . Instantaneous glucose fluxes were used to calculate the net glucose mass balance (mmol/session and g/session) achieved through the overall HDF session
assuming that operational conditions remained constant.
Serum glucose concentrations tended to increase post-HDF as a consequence of the glucose supplementation. However, no severe hyperglycaemia or tolerance problems were observed at any time. Serum glucose pre- and post-HDF rose from 4.9±0.8 to 6.6±1.5 mmol/l for the 24 sessions without glucose, and from 5.1±1.3 to 8.6±2.3 mmol/l for the 24 with glucose infusion (P<0.05). Glucose concentrations measured simultaneously at dialyser blood inlet and outlet, and in spent dialysate were respectively as follows: 5.0±0.7, 5.7±1.0 and 5.5±0.3 mmol/l in the absence of glucose infusion and 9.1±0.6, 7.1±0.6 and 8.1±0.5 mmol/l in the presence of glucose supplementation. Results comparing HDF sessions without and with glucose infusion are presented in Table 2. As shown, a virtually nil net glucose mass balance (5.9±35 mmol/session or 1.1±6.3 g/session) was noted in HDF sessions without glucose infusion while HDF sessions with glucose infusion induced a 346±88 mmol/session (62.4±16 g/session) negative glucose mass transfer.
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Total protein concentration was 66 g/l at dialyser inlet and 70 g/l at dialyser outlet in the absence of glucose infusion as compared to 67 g/l and 71 g/l respectively with glucose supplementation.
Furthermore, there was no significant change in serum sodium concentrations and blood osmolality (pre- vs post-HDF and sessions without vs with glucose). Pre-/post-session serum sodium was 139±2/143±1 mmol/l in HDF without glucose, and 141±2/137±2 mmol/l in HDF with glucose (P=NS (non significant) without vs with glucose). Pre-/post-blood osmolality was 312±9.6/301±3.5 without glucose, and 314±10.1/301±3.9 mosm/kgH2O (P=NS without glucose vs with glucose). Arterial blood pressure tended to be better maintained in HDF sessions when glucose was administered, although it did not reach statistical significance. Mean arterial pressure pre- and post-HDF declined from 101±23 to 78±16 mmHg for the 24 sessions without glucose, and from 97±20 to 83±17 mmHg for the 24 sessions with glucose.
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Discussion |
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Enhancement in solute clearances by 1015% with glucose administration observed in our study appears to be most probably a consequence of an increase in membrane water and/or solute fluxes. It translated into improved performance of HDF as evidenced by a significant increase of percentage reduction ratios, Kt/V, and SRI. Although not assessed in the present study, an evaluation of middle molecule elimination during HDF (with or without glucose supplementation) appears suitable to appreciate more extensively the overall gain in performance brought about by the glucose infusion. It is admitted that the formation of a protein layer onto the membrane under high convective flux affects its hydraulic permeability and decreases Kuf and solute removal by reducing the sieving coefficient of the membrane [57]. Blood viscosity, which is largely dependent on plasma protein concentration and haematocrit, has an impact on the magnitude of this phenomenon [1315]. Accordingly, one may wonder if the protein coating that develops at the surface of a polysulphone membrane during high-flux HDF could be altered by glucose administration, thereby reducing its negative impact on water and/or solute permeability.
This preliminary study does not provide a clear explanation for the enhanced ultrafiltration capacity of a polysulphone filter concomitant on glucose infusion in the venous blood return. A mechanical phenomenon is not likely since the continuous infusion should not affect pressure equilibrium in the dialyser. Anyway, the dialysis machine would keep the ultrafiltration at the desired rate by self-adjusting the transmembrane pressure and, indirectly, pressure in the dialysate compartment. It is recognized that an increase in dialysate sodium may result in a higher serum osmolality, permitting a better refilling of the intravascular compartment from interstitial and intracellular spaces [16,17]; this becomes potentially useful for haemodynamically unstable patients during haemodialysis [18]. On the other hand, glucose infused directly into the patient's blood induces a brisk increase in serum osmolality, accelerating refilling of the intravascular compartment, and consequently contributing to an increase in hydrostatic gradient across the membrane. Indeed, the observed tendency toward higher glycaemia with glucose supplementation would support this hypothesis. On-line volaemia monitoring was not performed during the course of this study, suppressing, by the way, arguments that would favour this hypothesis. However, glucose osmotic effect in non-diabetic patients (who easily release insulin and rapidly transfer glucose into cells) is not as sustained as for other osmotic agents, nor as in diabetic subjects. In the absence of prolonged hyperglycaemia, this explanation appears difficult to admit. Finally, the observed phenomenon could instead be attributed to a direct effect of glucose, and several hypotheses may be formulated. First, glucose may act as an osmotic agent that, freely passing the haemodiafilter membrane, induces a solvent drag effect, facilitating water and small solute removal. Negative glucose mass balance observed during an HDF session with glucose infusion may substantiate this hypothesis. Second, glucose may have a direct effect at the membrane level. Indeed, glucose may be adsorbed onto the membrane, reducing the protein-layer formation. Alternatively, glucose may interact with the chemical and/or electrical structure of the polysulphone membrane itself, altering its permeability performance. Nevertheless, the fact that the Kuf increase is a very early phenomenon favours a role of glucose acting as a solvent drag agent more than interfering at the membrane level with the protein-layer formation. Further, in-vitro and in-vivo studies exploring the role of glucose on haemodiafilter performance changes are needed for a better definition and understanding of such phenomena.
From a haemodynamic perspective, intradialytic administration of an osmotic agent such as hypertonic glucose can improve tolerance to haemodialysis and is routine practice in many units. Even if our objective was not to evaluate this particular aspect, a slight tendency toward better preserved post-session MAP was noted in patients receiving glucose supplementation, although it did not reach significance.
We conclude that glucose infusion in the venous blood return during haemodiafiltration using polysulphone membranes increases ultrafiltration performance by as much as 40% with a concomitant increment in dialysis dose by 1015%. This preliminary observation favours the osmotic role of glucose and its solvent drag action. However, a direct role of glucose at the membrane surface altering the protein layer formation and the membrane permeability may not be completely ruled out. Further studies are required to evaluate the impact of glucose on different types of membrane and to elucidate its beneficial role on haemodiafiltration performance.
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Acknowledgments |
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References |
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