Can regional anticoagulation with calcium-free dialysate be extended to maintenance hemodialysis?

BACKGROUND: Regional anticoagulation in hemodialysis avoids the use of heparin, which is responsible for both hemorrhagic and non-hemorrhagic complications. Typically, blood is decalcified by injecting citrate into the arterial line of the extracorporeal circuit. Calcium-free dialysate improves anticoagulation efficacy but requires injection of a calcium-containing solution into the venous line and strict monitoring of blood calcium levels. Recent improvements have made regional anticoagulation with calcium-free dialysate safer and easier. OBSERVATIONS: (1) Adjusting the calcium injection rate to ionic dialysance avoids the risk of dyscalcemia, thus making unnecessary the monitoring of blood calcium levels. This adjustment could be carried out automatically by the hemodialysis monitor. (2) As calcium-free dialysate reduces the amount of citrate required, this can be supplied by dialysate obtained from currently available concentrates containing citric acid. This avoids the need for citrate injection and the risk of citrate overload. (3) Calcium-free dialysate no longer needs the dialysate acidification required for avoiding calcium carbonate precipitation in bicarbonate-containing dialysate. CONCLUSIONS: Regional anticoagulation with calcium-free dialysate enables an acid- and heparin-free procedure that is more biocompatible and environmentally friendly than conventional bicarbonate hemodialysis. The availability of specific acid-free concentrates and adapted hemodialysis monitors is required to extend this procedure to maintenance hemodialysis.

Automated adjustment of dialysate sodium by the hemodialysis monitor: Rationale, implementation, and clinical benefits.

Prescribing dialysate sodium is the responsibility of the physician, but there are currently no clear guidelines for this prescription. Furthermore, there is quite frequently a significant difference between prescribed and measured dialysate sodium. Several arguments, both theoretical and experimental, suggest that dialysate sodium should be adjusted individually in such a way as to result in a decreasing sodium profile that takes into account the patient's predialytic natremia. The generalization in clinical routine of this strategy requires the integration into the hemodialysis monitor of software making the machine capable to automatically adjust the dialysate sodium at each session. The only three such softwares that have been integrated into hemodialysis machines for routine clinical use are discussed. All three work with conductivity measurements as a surrogate for sodium concentrations. Although there are only a few publications on the use of these softwares in clinical practice, they appear to result in improved intradialytic tolerance to the dialysis treatment, better control of hypertension, and reduced thirst, leading to decreased interdialytic weight gain.

Dialysate sodium management in hemodialysis and online hemodiafiltration: The single-pool kinetic model revisited.

BACKGROUND: Determining the optimal dialysate sodium remains one of the challenges of hemodialysis prescription. Several arguments suggest that the dialysate sodium should be individually adjusted according to the patient's natremia. This strategy is greatly facilitated by using an algorithm. Only three such algorithms have been embedded in hemodialysis machines for the widespread generalization of this strategy in clinical routine: the Diacontrol (Hospal-Baxter Healthcare Corp., Deerfield, IL, USA), the HFR-Aequilibrium (Bellco-Medtronic, Dublin, Ireland), and the Na-control (Fresenius Medical Care, Bad-Homburg, Germany). METHODS: Model the solute mass-transfer across the dialyzer membrane in online hemodiafiltration and adapt the Diacontrol algorithm based on a single-pool kinetic model of sodium balance for quantifying ionic balance and managing tonicity. RESULTS: (1) Substituting sodium measurements with conductivity measurements allows the control of tonicity which is a more physiological parameter than natremia. (2) Consideration of all ion exchanges as a whole and not just sodium exchange avoids some of the assumptions required by kinetic modeling of sodium balance. (3) Equations provided by the model are applicable to both hemodialysis and online hemodiafiltration. (4) The differences between this model used by Diacontrol and the models on which the other two software's (HFR-Aequilibrium and Na-control) are based are highlighted. CONCLUSIONS: The single-pool kinetic model developed for the management of natremia in hemodialysis is also valid for the management of tonicity for both conventional hemodialysis and all online hemodiafiltration procedures.

Routine online assessment of dialysis dose: Ionic dialysance or UV-absorbance monitoring?

For three-weekly hemodialysis, a single-pool Kt/V target of at least 1.4 together with a minimal dialysis dose Kt at 45 L for men and 40 L for women per each session is currently recommended. Fully automatic online calculation of Kt and Kt/V from conductivity or UV-absorbance measurements in the dialysate is standardly implemented on some hemodialysis monitors and makes it possible to estimate the dialysis dose without the need for blood or dialysate samples. Monitoring the UV-absorbance of the spent dialysate is the most direct method for estimating Kt/V as it does not require an estimate of V. Calculation of ionic dialysance from conductivity measurements is the most direct method for estimating Kt and BSA-scaled dialysis dose. Both ionic dialysance monitoring and UV-absorbance monitoring may help detect a change in urea clearance occurring during the session, but this change must be interpreted differently depending on the monitoring being considered. An abrupt decrease in urea clearance results in a decrease in ionic dialysance but, paradoxically, a sudden increase in estimated urea clearance provided by dialysate UV-absorbance monitoring. Healthcare teams who monitor both ionic dialysance and UV-absorbance in their hemodialysis units must be clearly informed of this difficulty.

Mathematical model to predict B-type natriuretic peptide levels in haemodialysis patients.

AIM: Clinical interpretation of B-type natriuretic peptide (BNP) levels in haemodialysis (HD) patients for fluid management remains elusive. METHODS: We conducted a retrospective observational monocentric study. We built a mathematical model to predict BNP levels, using multiple linear regressions. Fifteen clinical/biological characteristics associated with BNP variation were selected. A first cohort of 150 prevalent HD (from September 2015 to March 2016) was used to build several models. The best model proposed was internally validated in an independent cohort of 75 incidents HD (from March 2016 to December 2017). RESULTS: In cohort 1, mean BNP level was 630 ± 717 ng/mL. Cardiac disease (CD - stable coronary artery disease and/or atrial fibrillation) was present in 45% of patients. The final model includes age, systolic blood pressure, albumin, CD, normo-hydrated weight (NHW) and the fluid overload (FO) assessed by bio-impedancemetry. The correlation between the measured and the predicted log-BNP was 0.567 and 0.543 in cohorts 1 and 2, respectively. Age (ß = 3.175e-2 , P < 0.001), CD (ß = 5.243e-1 , P < 0.001) and FO (ß = 1.227e-1 , P < 0.001) contribute most significantly to the BNP level, respectively, but within a certain range. We observed a logistic relationship between BNP and age between 30 and 60 years, after which this relationship was lost. BNP level was inversely correlated with NHW independently of CD. Finally, our model allows us to predict the BNP level according to the FO. CONCLUSION: We developed a mathematical model capable of predicting the BNP level in HD. Our results show the complex contribution of age, CD and FO on BNP level.

[The different modalities of isonatric hemodialysis]. / Hémodialyse isonatrique : principe et modalités.

Setting dialysate sodium allows to adequately adjust sodium balance and plasma sodium at the end of dialysis session. In accordance with the set-point theory based on the concept of restoring cellular hydration, an adequate target for plasma sodium at the end of the session could be the value of predialysis plasma sodium concentration (isonatric hemodialysis). Some recently available dialysis monitors provide an on-line value of plasma-water conductivity usually converted in on-line natremia. There are different modalities of isonatric hemodialysis depending on whether the online value of natremia is used or not. By reviewing the few studies concerning the isonatric hemodialysis, it seems logical to set a target of postdialysis on-line natremia (or plasma-water conductivity) slightly lower than its predialysis value. However this strategy requires specifically designed software not yet available in clinical routine.

[Technological innovations in dialysis]. / Innovations technologiques en dialyse.

The history of dialysis, which started only half a century ago, is rich in developments and technological innovations. Thanks to scientific progress and the development of knowledge in the field of dialysis, patient survival will continue to increase and quality of life will continue to improve. More precise purification, reductions in the size and weight of equipment as well as refinement of filtration membranes are a few of the recent and current breakthroughs, and are challenges for further development. Dialysis has a world of opportunities ahead in terms of optimizing processes and new innovations, continuing the progress made in improving patient treatment conditions. Cet article fait partie du numéro supplément Innovations en Néphrologie réalisé avec le soutien institutionnel de Vifor Fresenius Medical Care Renal Pharma.

From Isonatric to Isotonic Hemodialysis.

BACKGROUND: Isonatric hemodialysis aims at maintaining stable cellular hydration through a close control of natremia, considered a surrogate of tonicity. However, 2 methods are available to perform isonatric hemodialysis: one based on natremia derived from plasma conductivity (NaCond) and the other based on natremia measured at laboratory (NaLab). We compared the control of tonicity obtained by isonatric hemodialysis based on NaLab or NaCond. METHODS: Changes in tonicity NaLab and NaCond were recorded during 55 hemodialysis sessions. Sessions were divided according to the variation of tonicity: hypotonic sessions (tonicity decrease ≥2 mOsm/kg); isotonic sessions (tonicity variation <2 mOsm/kg); hypertonic sessions (tonicity increase ≥2 mOsm/kg). RESULTS: During isotonic hemodialysis, NaCond decreases significantly by 1 mmol/L, whereas NaLab remained stable. CONCLUSIONS: Isonatric hemodialysis based on NaLab and isonatric hemodialysis based on NaCond is to be distinguished. Isotonic hemodialysis could be performed by decreasing NaCond by 1 mmol/L or maintaining NaLab stability.

Natremia, tonicity, and conductivity measurements in hemodialyzed patients.

PURPOSE: Natremia is usually considered to reflect tonicity in non-hemodialyzed patients. Some hemodialysis monitors provide an online value (NaCond) of natremia calculated from conductivity measurements. This study compared the relation between tonicity and natremia (NaLab) measured at laboratory with the relation between tonicity and NaCond in hemodialysis patients. METHODS: Fifty-five hemodialysis sessions performed with a Fresenius 5008 dialysis monitor (Fresenius Medical Care, Bad Homburg, Germany) providing a value of NaCond were analyzed. Tonicity (calculated as "osmolality - urea"), NaLab and NaCond were measured at the beginning and end of sessions. RESULTS: The r2 correlation-coefficient between tonicity and NaLab is 0.48 (n = 110). The correlation between tonicity and NaCond is stronger (r2 =  0.71). CONCLUSIONS: Conductivity measurements provide a natremia value (NaCond) that is a better surrogate for tonicity than natremia measured at laboratory. Because NaCond is not obtained from sodium measurement, dialysis monitors should display a value for plasma conductivity (mS/cm) instead for natremia (mmol/l).

[Online hemodiafiltration: is it really more expensive?]. / Hémodiafiltration en ligne : y a-t-il réellement un surcoût ?

Online hemodiafiltration has been shown to have many benefits in terms of morbi-mortality and to increase middle weight molecules removal. However, this technique is supposed to have an additional cost which may be an obstacle to increase its development in hemodialysis centers. The aim of the study is to achieve an accurate pharmaco-economic evaluation for determining the real overcost of online hemodiafiltration (OL-HDF) in comparison with high flux hemodialysis (HF-HD) using standard priming. We have identified the additional costs related to the consumables and monitors and the additional costs imposed by the technique itself (water consumption and microbiological analysis). In the center, more than 28,000 sessions per year are performed with 70% in OL-HDF (90% post-dilution). The consumable overcost ranges from -2.55 to +3.35 euros per session depending on the monitor and on the HDF modality. The overcost of microbiological analysis is +1.1 euros per session. The theoretical additional water consumption is calculated from different dialysat flow rates and OL-HDF modality. Its ranges from +50.8L to +74.8L per session increasing the water overcost from +0.15 to +0.23 euros per session. This accurate evaluation shows that the cost difference of OL-HDF depends on monitor used and on the OL-HDF modality. In our center, it ranges from -1.29 to +4.58 euros per session.

Ionic dialysance and determination of Kt/V in on-line hemodiafiltration with simultaneouspre- and post-dilution.

PURPOSE: A direct determination of Kt/V using ionic dialysance for estimating K and bio-impedancemetry for estimating V is compared with the usual indirect estimation based on the second generation Daugirdas equation during a new technique of hemodiafiltration with simultaneous pre- and post-dilution (mixed-HDF).
 METHODS: In 31 informed consented patients, the urea distribution volume (V) is estimated by total body water (VBCM ) measured by the Body Composition Monitor (BCM; Fresenius Medical Care, Bad Homburg, Germany) based on bio-impedance spectroscopy. The value (KOCM t)/VBCM is calculated during 114 mixed-HDF sessions (duration 4 hours) from the measurement of ionic dialysance KOCM by the OCM module, standard on the 5008 dialysis monitor (Fresenius Medical Care, Germany). The single pool (Kt/V)sp is determined from blood urea concentration measurements using the Daugirdas equation. RESULTS: Mixed-HDF is a very high-efficiency hemodialysis with a delivered dialysis dose Kt/V near from 2 per 4-hour session. (KOCM t)/VBCM (1.97 ± 0.28) is consistent with (Kt/V)sp (2.01 ± 0.34) with a correlation coefficient at 0.72. CONCLUSIONS: Direct calculation of Kt/V from estimating K by OCM and V by BCM is consistent with the usual indirect estimation by the second generation Daugirdas equation. Therefore, the regular determination of V by BCM allows the estimation of single-pool Kt/V at each session without the need of blood sampling.

[Disorders in sodium-water balance]. / Anomalies de l'équilibre hydrosodé

Water balance control is aimed at normalizing cellular hydration, and sodium balance control at normalizing extracellular volume. Water balance control is based on the regulation of body fluid tonicity, while the control of sodium balance is based on the regulation of effective arterial volume. Disorders of water balance act on cellular hydration: primary disorders induce a proportional change in tonicity; secondary disorders are induced by a change in tonicity or effective arterial volume. Disorders of sodium balance act on extracellular volume: primary disorders of sodium balance induce a change in effective arterial volume; secondary disorders are induced by a change in effective arterial volume. Physical examination of the patient allows assessing the extracellular volume and the severity of the sodium balance disorder. Natremia - that generally reflects tonicity - allows to assess cellular hydration and to determine the type of water balance disorder. In the case of natremia disturbance, the assessment of both the tonicity and the extracellular volume allows the determination of the type of water and/or sodium balance disorder that is necessary for prescribing the adequate therapy.

Effect of a plasma sodium biofeedback system applied to HFR on the intradialytic cardiovascular stability. Results from a randomized controlled study.

BACKGROUND: Intradialytic hypotension (IDH) is still a major clinical problem for haemodialysis (HD) patients. Haemodiafiltration (HDF) has been shown to be able to reduce the incidence of IDH. METHODS: Fifty patients were enrolled in a prospective, randomized, crossover international study focussed on a variant of traditional HDF, haemofiltration with endogenous reinfusion (HFR). After a 1-month run-in period on HFR, the patients were randomized to two treatments of 2 months duration: HFR (Period A) or HFR-Aequilibrium (Period B), followed by a 1-month HFR wash-out period and then switched to the other treatment. HFR-Aequilibrium (HFR-Aeq) is an evolution of the haemofiltration with endogenous reinfusion (HFR) dialysis therapy, with dialysate sodium concentration and ultrafiltration rate profiles elaborated by an automated procedure. The primary end point was the frequency of IDH. RESULTS: Symptomatic hypotension episodes were significantly lower on HFR-Aeq versus HFR (23 ± 3 versus 31 ± 4% of sessions, respectively, P l= l0.03), as was the per cent of clinical interventions (17 ± 3% of sessions with almost one intervention on HFR-Aeq versus 22 ± 2% on HFR, P <0.01). In a post-hoc analysis, the effect of HFR-Aeq was greater on more unstable patients (35 ± 3% of sessions with hypotension on HFR-Aeq versus 71 ± 3% on HFR, P <0.001). No clinical or biochemical signs of Na/water overload were registered during the treatment with HFR-Aeq. CONCLUSIONS: HFR-Aeq, a profiled dialysis supported by the Natrium sensor for the pre-dialysis Na(+) measure, can significantly reduce the burden of IDH. This could have an important impact in every day dialysis practice.

Isonatric dialysis biofeedback in hemodiafiltration with online regeneration of ultrafiltrate (HFR): rationale and study protocol for a randomized controlled study.

Dialysate sodium prescription has major implications for hemodialysis tolerance but also for dialyzed patients' cardiovascular morbidity as a determinant factor of blood pressure. Biofeedback systems have been developed to drive dialysate conductivity in order to reach a prescribed serum sodium concentration, indirectly evaluated by a dialysate or an ultrafiltrate conductivity measurement. A biofeedback system using hemodiafiltration with online regeneration of ultrafiltrate (HFR) has been specially developed with an isonatric mode maintaining an equal serum sodium concentration between start and end of the dialysis session, combined with ultrafiltration and conductivity profiles. We hypothesized that using this biofeedback in an isonatric mode would have a beneficial effect on blood pressure and dialysis tolerance. The study protocol has been approved by our ethics committee and is presented herein.

Safe use of citric acid-based dialysate and heparin removal in postdilution online hemodiafiltration.

BACKGROUND: Anticoagulation of the blood circuit with heparin is essential for hemodialysis, but exposes patients to several risks (bleeding, thrombocytopenia, etc.). The use of citric acid-based dialysate (CitA-D) allows the reduction of heparin in conventional hemodialysis. We evaluated the feasibility of using CitA-D in postdilution online hemodiafiltration (OL-HDF) and of removing heparin. METHODS: We prospectively compared chlorhydric acid-based dialysate with CitA-D in 10 patients treated by OL-HDF. First, we reduced heparin by half the dose and then we totally removed anticoagulation. RESULTS: For all 120 sessions using heparin-free CitA-D, only one clotting episode related to an arteriovenous fistula stenosis was observed. No adverse clinical effect was observed. (Kt/V)sp, predialytic serum bicarbonate, calcium, phosphate, parathroid hormone, and ß2-microglobulin remained the same in all cases. CONCLUSION: Our data suggest that the use of CitA-D in OL-HDF is safe and allows heparin removal in most patients.

[Acetate-free hemodialysis: what does it mean?]. / Hémodialyse sans acétate: qu'est-ce vraiment?

Substituting bicarbonate by acetate in dialysis fluids has been proposed for avoiding precipitation of calcium and magnesium carbonates. However, acetate hemodialysis has been abandoned because of deleterious effects of acetate. Conventional bicarbonate hemodialysis is not totally acetate-free, because 3 to 7 mEq/l of acetic acid are added to the dialysate. Acetate-free hemodialysis is possible with another acid (chlorhydric acid or citric acid) or without acid by using some techniques of low-efficiency hemodiafiltration, as acetate-free biofiltration, which avoids the deleterious effect of blood acidification into the dialyzer. In this paper, advantages and disadvantages of different techniques of acetate-free hemodialysis are discussed.

[Estimation of urea distribution volume in hemodialysis patients]. / Estimation du volume de distribution de l'urée chez le patient hémodialysé.

BACKGROUND: On-line urea clearance estimation, currently available on some dialysis monitors, makes it possible to calculate the dialysis dose Kt and thus allows to estimate Kt/V for each session, providing an estimation of urea distribution volume (V) at equilibrium assumed equal to total body water. METHODS: Three methods suitable for routinely estimating V, using the anthropometric Watson formula (V(Wat)), the body composition monitor (BCM) device (Fresenius Medical Care) based on bio-impedance analysis (V(imp)) and the indirect estimation (V(Daug)) obtained from measurement of Kt/(Kt/V)(sp) ratio respectively are compared during 25 dialysis sessions in 15 patients to a direct estimation (V(DDQ)) obtained by direct quantification of dialysis (DDQ) considered as the gold standard in hemodialysis patient.. RESULTS: V(Watson) overestimates V(DDQ) by about 20%. The values of V(imp) (29.1±5.6 L) and V(Daug) (29.5±4.6 L) are in agreement with V(DDQ) (29.9±5.2 L). Correlation coefficient with V(DDQ) is better for V(imp) (r=0.94) than for V(Daug) (r=0.85). CONCLUSION: Bio-impedancemetry using BCM and indirect method using the second generation Daugirdas equation are two methods of clinical interest for estimating V. Bio-impedancemetry does not require blood sample, but it needs to have a specific device at disposal.

[Technical advances in haemodialysis]. / Nouveautés techniques en hémodialyse.

Survival improvement of our haemodialysis patients is partly due to technologic improvement of the dialysis therapy. High permeability membranes and bicarbonate dialysate were the most relevant of past decades. What are the present technologic innovations that will provide clinical benefit? Acetate-free biofiltration, biofeedback systems, better haemodiafiltration techniques and techniques with adsorption could be part of them.

Measuring plasma conductivity to detect sodium load in hemodialysis patients.

BACKGROUND: Sodium thiosulfate therapy has been proposed for calcific uremic arteriolopathy and nephrogenic systemic fibrosis in hemodialysis patients. The treatment brings 3.7 g (161 mmol) of sodium. How to counterbalance this sodium load was studied. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma conductivity (Cp) and mass balance index were compared for 20 sessions without thiosulfate and 20 sessions with thiosulfate infusion. Subsequently, the dialysate conductivity was set to 13.8 mS/cm during the entire session. Next, dialysate conductivity was set to 14 mS/cm for the first 3 h and to 13 mS/cm for the last hour of thiosulfate infusion (n = 25). RESULTS: The Cp variation between beginning and end was equal to +0.005 +/- 0.13 mS/cm without thiosulfate, +0.24 +/- 0.13 mS/cm with thiosulfate, and 14 mS/cm dialysate conductivity (P < 0.001). The decrease in dialysate conductivity at 13.8 mS/cm did not counterbalance the sodium load. The last program adequately compensated the sodium load with a Cp increase of only +0.05 +/- 0.14 mS/cm (NS versus without thiosulfate). The total of the dialyzed sodium and the sodium load for this last program was equal to 603 mmol compared with 456 mmol for the sessions without thiosulfate, the difference of 147 mmol being close to the known content of 161 mmol in 25 g of infused thiosulfate. CONCLUSIONS: Thiosulfate infusion requires a decrease of dialysate conductivity of -1 mS/cm during the infusion to counterbalance the added 3.7 g (161 mmol) sodium load.