Automated individualization of dialysate sodium concentration reduces intradialytic plasma sodium changes in hemodialysis

In standard care, hemodialysis patients are often treated with a center‐specific fixed dialysate sodium concentration, potentially resulting in diffusive sodium changes for patients with plasma sodium concentrations below or above this level. While diffusive sodium load may be associated with thirst and higher interdialytic weight gain, excessive diffusive sodium removal may cause intradialytic symptoms. In contrast, the new hemodialysis machine option “Na control” provides automated individualization of dialysate sodium during treatment with the aim to reduce such intradialytic sodium changes without the need to determine the plasma sodium concentration. This proof‐of‐principle study on sodium control was designed as a monocentric randomized controlled crossover trial: 32 patients with residual diuresis of ≤1000 mL/day were enrolled to be treated by high‐volume post‐dilution hemodiafiltration (HDF) for 2 weeks each with “Na control” (individually and automatically adjusted dialysate sodium concentration) versus “standard fixed Na” (fixed dialysate sodium 138 mmol/L), in randomized order. Pre‐ and post‐dialytic plasma sodium concentrations were determined at bedside by direct potentiometry. The study hypothesis consisted of 2 components: the mean plasma sodium change between the start and end of the treatment being within ±1.0 mmol/L for sodium‐controlled treatments, and a lower variability of the plasma sodium changes for “Na control” than for “standard fixed Na” treatments. Three hundred seventy‐two treatments of 31 adult chronic hemodialysis patients (intention‐to‐treat population) were analyzed. The estimate for the mean plasma sodium change was ?0.53 mmol/L (95% confidence interval: [?1.04; ?0.02] mmol/L) for “Na control” treatments and ?0.95 mmol/L (95% CI: [?1.76; ?0.15] mmol/L) for “standard fixed Na” treatments. The standard deviation of the plasma sodium changes was 1.39 mmol/L for “Na control” versus 2.19 mmol/L for “standard fixed Na” treatments (P = 0.0004). Whereas the 95% CI for the estimate for the mean plasma sodium change during “Na control” treatments marginally overlapped the lower border of the predefined margin ±1.0 mmol/L, the variability of intradialytic plasma sodium changes was lower during “Na control” versus “standard fixed Na” treatments. Thus, automated dialysate sodium individualization by “Na control” approaches isonatremic dialysis in the clinical setting.     

The Choice of Dialysate Sodium is Influenced by Hemodialysis Frequency and Duration: What Should It Be and For What Modality?

Cardiovascular disease is the leading cause of mortality in hemodialysis patients. A chronic state of volume and pressure overload contributes, and central to this is the net sodium balance over the course of a hemodialysis. Of recent interest is the contribution of the dialysate sodium concentration (Dial‐Na+) to clinical outcomes. Abundant evidence confirms that in thrice‐weekly conventional hemodialysis, higher Dial‐Na+ associates with increased intradialytic weight gain, blood pressure, and cardiovascular morbidity and mortality. On the other hand, low Dial‐Na+ associates with intradialytic hypotension in the same patient population. However, the effect of Dial‐Na+ in short hours daily hemodialysis (SHD; often referred to as “quotidian” dialysis), or nocturnal dialysis (FHND) is less well studied. Increased frequency and duration of exposure to a diffusive sodium gradient modulate the way in which DPNa+ alters interdialytic weight gain, predialysis blood pressure, and intradialytic change in blood pressure. Furthermore, increased dialysis frequency appears to decrease the predialysis plasma sodium setpoint (SP), which is considered stable in conventional thrice‐weekly patients. This review discusses criteria to determine optimal Dial‐Na+ in conventional, SHD and FHND patients, and identifies areas for future research.     

Sodium modeling in hemodiafiltration.

A computer model was developed to simulate sodium and water kinetics during hemodiafiltration (HDF), acetate-free biofiltration (AFB) and hemodialysis (HD). Multiple regression analysis of the results of 3,240 simulated applications of the model (1,620 HDF, 1,080 AFB, 540 HD) showed that, during HDF and AFB, there is a close correlation (R2 = 0.92 and 0.91) between plasma water sodium concentration [( Na+P]) and a set of three variables: 1) the sodium gradient between plasma water and dialysate, 2) the sodium concentration of the substitution fluid and 3) ultrafiltration (UF) rate. With HD, a close correlation (R2 = 0.94) was found between changes in [Na+P] and combined changes in sodium gradient and the UF rate. On this basis, a regression equation was formulated for each procedure which allowed a reliable prediction of final [Na+P] to be made on the basis of knowledge of the imposed Na gradient, the programmed infusion (during HDF and AFB), and the UF rate. Clinical validation of the model was obtained in 12 patients: predicted final [Na+P] agreed well with the values measured by means of direct potentiometry (141.9 vs. 142.1 mEq/liter; P = NS), with a mean difference (-0.16 mEq/liter) and limits of agreement (+0.8 to -1.03 mEq/liter) fully acceptable for clinical purposes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sodium balance in hemodialysis therapy

Water and sodium overload is the predominant factor in the pathogenesis of hypertension in dialysis patients. In many dialysis patients, dry weight is not reached because of an imbalance between the interdialytic accumulation of water and sodium and the brief and discontinuous nature of routine dialysis therapy. During dialysis, sodium is removed by convection and to a lesser degree by diffusion. However, with supraphysiologic dialysate sodium concentrations, diffusive influx from dialysate may occur, especially in patients with low predialytic plasma sodium concentrations. Measuring sodium removal during dialysis is difficult and hampered by the variability in conventional sodium measurements. Ionic mass removal by continuous measurement of conductivity in the dialysate ports appears to be a promising tool for the approximation of sodium removal during dialysis. While the beneficial effects of concomitant water and sodium removal on blood pressure control in dialysis patients are undisputed, it is less well known whether a change in hydrosodium balance solely by reducing dialysate sodium is beneficial. Considering the inherent dangers of such an approach (intradialytic hemodynamic instability), the beneficial effects of strict dietary sodium restriction appear to be of much larger clinical benefit. It has become possible to individualize dialysate sodium concentration by means of online measurements of plasma conductivity and adjustment of dialysate conductivity by feedback technologies. The clinical benefits of this approach deserve further study. Still, reducing dietary sodium intake remains the most important tool in improving blood control in dialysis patients.     

Solute kinetics in hypertonic hemodiafiltration and standard hemodialysis

Hemodiafiltration (HDF) is a new dialysis treatment that combines convective and diffusive forces. In order to assess the efficiency of a peculiar model of hypertonic HDF (H HDF), we studied eight uremic patients when they were undergoing five sessions of H HDF of 180 minutes duration and two sessions of standard hemodialysis (HD) of 270 minutes duration with a comparable blood (approximately 400 mL/min) and dialysate flow rate (approximately 520 mL/min). The plasma water clearances (Kw) of small [urea (U), creatinine (C), uric acid (UA), and phosphorus (P)] and middle molecules [netilmicin (N) and inulin (I)] were exceedingly higher in H HDF than in HD; however, because of the different treatment times, U and C removal (R) in HD overcame and UA and P R in HD equalized that in H HDF. The factor time was not sufficient to HD to compensate for the large difference in Kw in the case of I. Additional studies were performed in seven out of the eight patients after two sessions of H HDF and one session of HD. Two significantly higher rebounds were observed when comparing both treatments: for U after HD and for parathyroid hormone (PTH) after H HDF; however, PTH Cx/Cs ratios (ratios of the plasma water concentration of PTH at any postdialysis time to the plasma water concentration of PTH at the start of the run) were not different in both treatments, meaning that there was an increased PTH secretion in the early post H HDF hours in order to compensate for the larger PTH R with H HDF.(ABSTRACT TRUNCATED AT 250 WORDS)     

New reinfusate composition in high UF haemodiafiltration: electrolyte solution combined with bicarbonate

When high-permeability membranes are employed, high UF shouldbe used in order to obtain optimal uraemic toxin removal andto avoid backfiltration. A high UF requires the infusion ofan electrolyte solution including Ca²⁺ and Mg²⁺ which cannotbe associated with bicarbonate in prepackaged solutions becauseof the risk of precipitation; therefore acetate or lactate areused as buffers. This study evaluated whether bicarbonate can be infused togetherwith an electrolyte solution in high UF HDF, and if so, theclinical advantages that could be obtained by substituting acetatewith bicarbonate in the reinfusate. In 12 patients on postdilutional high UF (121±10 ml/min)HDF (Qb 400, Qd 500 ml/min, dialysate containing Na, 141 ±2;K, 2.5; Ca, 3.5; Mg, 0.7; Cl, 111±2; acetate, 3; bicarbonate,34 mEq/1; TMP 400 mmHg), an acid bag (Na, 128; K, 4; Ca, 7;Mg, 2; Cl, 141; acetate, 8 mEq/1), and a basic bag (Na, 150;HCO₃, 80; Cl, 70 mEq/1), each containing 2 litres, were simultaneouslyinfused through a Y connection. The final composition of reinfusate at the drip-chamber, combinedwith the above dialysate, allowed a negative intradialytic massbalance for Na, K, Mg and a positive one for Ca, acetate, tomaintain pre-postdialytic plasma values of these ions as wellas bicarbonate close to normal limits. Furthermore, in five high-risk patients, clinical data wereevaluated on high UF HDF, infusing a solution containing eitheracetate or bicarbonate, and an improvement of vascular stabilitywas observed with the bicarbonate reinfusate. Therefore, in high UF HDF, bicarbonate can be infused alongwith an electrolyte solution, avoiding unphysiological levelsof other buffers, and improving vascular stability in high-riskpatients.     

Haemodialysis with on-line monitoring equipment: tools or toys?

BACKGROUND: On-line monitoring of chemical/physical signals during haemodialysis (HD) and bio-feedback represents the first step towards a 'physiological' HD system incorporating adaptive and logic controls in order to achieve pre-set treatment targets. METHODS: Discussions took place to achieve a consensus on key points relating to on-line monitoring and bio-feedback, focusing on the clinical applications. RESULTS: The relative blood volume (BV) reduction during HD can be monitored by optic devices detecting the variations in concentration of haemoglobin/haematocrit. BV changes result from an equilibrium between ultrafiltration and the refilling capacity. However, BV reduction has little power in predicting intra-HD hypotensive episodes, while the combination of the patient-dialysate sodium gradient, the relative BV reduction between the 20th and 40th minute of HD, the irregularity of the profile of BV reduction over time and the heart rate decrease from the start to the 20th minute of HD predict intra-HD hypotension with a sensitivity of 82%, a specificity of 73% and an accuracy of 80%. A bio-feedback system drives the relative BV reduction according to desired values by instantaneously changing the ultrafiltration rate and the dialysate conductivity. This system has proved to reduce the incidence of intra-HD hypotension episodes significantly. Ionic dialysance and the patient's plasma conductivity can be calculated easily from on-line inlet and outlet dialysate conductivity measurements at two different steps of dialysate conductivity. Ionic dialysance is equivalent to urea clearance corrected for recirculation and is a tool for continuously monitoring the dialysis efficiency and detecting early problems with the delivery of the prescribed dose of dialysis. Given the strict and linear relationship between conductivity and sodium content, the conductivity values replace the sodium concentration values and this permits the development of a conductivity kinetic model, by means of which sodium balance can be achieved at each dialysis session. The conductivity kinetic model has been demonstrated to improve intra-HD cardiovascular stability in hypotension-prone patients significantly. Ionic dialysance is also a useful tool to monitor vascular access function, as it can be used to obtain serial measurements of vascular access blood flow. On-line urea monitors provide detailed information on intra-HD urea kinetics and delivered dialysis dose, but they are not in widespread use because of the costs related to the disposable materials (e.g. urease cartridge). The body temperature monitor measures the blood temperature at the arterial and venous lines of the extra-corporeal circuit and, thanks to a bio-feedback system, is able to modulate the dialysate temperature in order to influence the patient's core body temperature, which can be kept at constant values. This is associated with improved intra-HD cardiovascular stability. The module can also be used to quantify total recirculation. CONCLUSIONS: On-line monitoring devices and bio-feedback systems have evolved from toys for research use to tools for routine clinical application, particularly in patients with clinical complications. Conductivity monitoring appears the most versatile tool, as it permits quantification of delivered dialysis dose, achievement of sodium balance and surveillance of vascular access function, potentially at each dialysis session and without extra cost.     

An Update on Intradialytic Cardiac Dysfunction

Cardiac dysfunction is a key factor in the high morbidity and mortality rates seen in hemodialysis (HD) patients. Much of the dysfunction is manifest as adverse changes in cardiac and vascular structure prior to commencing dialysis. This adverse vascular remodeling arises as a dysregulation between pro‐ and antiproliferative signaling pathways in response to hemodynamic and nonhemodynamic factors. The HD procedure itself further promotes cardiomyopathy by inducing hypotension and episodic regional cardiac ischemia that precedes global dysfunction, fibrosis, worsening symptoms, and increased mortality. Drug‐based therapies have been largely ineffective in reversing HD‐associated cardiomyopathy, in part due to targeting single pathways of low yield. Few studies have sought to establish natural history and there is no framework of priorities for future clinical trials. Targeting intradialytic cardiac dysfunction by altering dialysate temperature, composition, or ultrafiltration rate might prevent the development of global cardiomyopathy, heart failure, and mortality through multiple pathways. Novel imaging techniques show promise in characterizing the physiological response to HD that is a unique model of repetitive ischemia‐reperfusion injury. Reducing HD‐associated cardiomyopathy may need a paradigm shift from empirical delivery of solute clearance to a personalized therapy balancing solute and fluid removal with microvascular protection. This review describes the evidence for intradialytic cardiac dysfunction outlining cardioprotective strategies that extend to multiple organs with potential impacts on exercise tolerance, sleep, cognitive function, and quality of life.     

Comparison of predilution hemodiafiltration and low-flux hemodialysis at temperature-controlled conditions using high calcium-ion concentration in the replacement and dialysis fluid

BACKGROUND: It is the prevailing view that convective dialysis techniques stabilize blood pressure. The aim of this study was to compare the hemodynamics of high-dose predilution hemodiafiltration (HDF) and low-flux hemodialysis (HD), under matched conditions and using high calcium-ion concentration in the replacement/dialysis fluid. METHODS: 13 stable hemodialysis patients were investigated in a randomized crossover, blinded controlled trial. The patients were allocated to one session of predilution HDF (substitution fluid 1.20 1/kg BW) and one session of HD at 4.5 hours. At the start of the dialysis the patient's core temperature was "locked" by an automatic feedback system regulating the dialysate temperature, thereby patient's temperature was kept stable throughout the whole treatment. The Ca ion concentration in the substitution/dialysis fluid was 1.75 mM. Cardiac output was measured hourly by the ultrasound velocity dilution method. RESULTS: Within treatments comparisons revealed that both treatments displayed stable mean blood pressure and equally reduced cardiac output. HDF showed decreased stroke volume and increased total peripheral resistance. The pulse rate decreased significantly only during HD. Arterial temperature was kept constant during both treatments. Ultrafiltration volume, cardiopulmonary recirculation, relative blood volume, Kt/V and total energy transfer were matched for HD and HDF. The overall between treatments comparisons revealed no significant differences. CONCLUSIONS: We have shown that during matched conditions and high calcium concentrations, the hemodynamic profiles of high dose predilution HDF and lowflux HD were similar. Both modalities showed stable mean blood pressure profiles. An acute circulatory benefit of convective solute removal over diffusive, could not be demonstrated.     

Clinical Use of Profiled Hemodialysis

The new population on dialysis today consists mainly of high risk patients (the elderly, diabetics, etc.) with high cardiovascular scores, and such vascular pathology is the most important predisposing factor for the occurrence of a frequent intradialytic clinical complication, vascular instability syndrome, which covers a range of clinical problems. Recently a new dialysis technique, profiled hemodialysis (PHD), has been set up and proposed for routine use. PHD consists of the clinical use of preestablished individual dialysis profiles aimed at antagonizing the changes in intradialytic plasma osmolarity by continuous modulation of dialysate sodium concentration throughout the whole extracorporeal session. In particular, PHD aims at reducing the fall of plasma osmolarity in the first half of the session (when it is higher) by reducing the sodium removal rate through increasing its dialysate concentration while taking into account the desired individual sodium balance to be reached at the end of the session. In this work, we report clinical experience with PHD compared to standard hemodialysis with constant sodium dialysate (SHD) in terms of its efficacy to maintain a more stable intradialytic blood volume (BV) and more stable hemodynamics. The PHD used in this work has been implemented by a mathematical model for computing the individual dialysate sodium profile which we have recently validated (Ursino M, Colì L, La Manna G, Grilli Cicilioni M, Dalmastri V, Guidicissi A, Masotti P, Avanzolini G, Stefani S, Bonomini V. A simple mathematical model of intradialytic sodium kinetics: “in vivo” validation during hemodialysis with constant or variable sodium. Int J Artif Organs 1996; 19:393–403.). Eleven uremic patients affected by hypotension at the beginning of dialysis treatment were studied. Each patient first underwent an SHD treatment and 1 week later a PHD treatment. The 2 extracorporeal sessions (one on SHD and the other on PHD) were performed in each individual patient under identical operative conditions including the sodium mass removal by the end of the session and the ultrafiltration rate. The crit line and Doppler echocardiography were used to determine BV, cardiac output (CO), and stroke volume (SV) throughout the sessions. The mean blood pressure (MBP) and heart rate (HR) were simultaneously monitored. PHD was associated with a more stable intradialytic BV and more stable hemodynamics compared to SHD. The higher stability of BV and cardiac function (in terms of SV and CO maintenance) which was obtained above all in the first half of the PHD session was associated with a higher stability of the MBP and the HR. This resulted in an enhancement in cardiovascular tolerance to ultrafiltration throughout the session in all tested patients. In contrast, SHD in the same patients was characterized by early significant changes in BV and cardiovascular parameters resulting in a significant decrease of the MBP and a significant increase of the HR throughout the session and also 1 h after the end of dialysis. Our results indicate that PHD may represent an efficient approach for the treatment of patients suffering from intradialytic vascular instability. If long-term clinical practice confirms the efficacy of PHD in controlling dialysis intolerance symptoms, it will have great scope as a routine procedure.     

Study on Sodium and Potassium Balance During Hemodialysis

It is the goal of this section to publish material that provides information regarding specific issues, aspects of artificial organ application, approach, philosophy, suggestions, and/or thoughts for the future.
Abstract: To acquire data for adequate ultrafiltration (UF) control, sodium and potassium balance was investigated during hemodialysis (HD) in 16 hemodialyzed patients. Overall balances were evaluated from concentration measurements of the in- and outflowing dialysate and pre- and postdialysis plasma. The diffusive and convective part of the electrolyte removal and its intra- and extracellular space (ICS, ECS) component were calculated. During a 5-h HD, 40–110 mmol of potassium is removed, predominantly by diffusion (72–88%). Calculation shows that 40–70% of the removed amount is taken from the ICS. Sodium's overall HD showed much higher scatter, ranging from positive values to 500 mmol removal. The diffusive component was positive in most cases. By ultrafiltration sodium is removed in all cases. Calculations also showed in all cases that sodium was delivered to the ICS. This is in contradiction with the general belief that exchangeable sodium is distributed solely in ECS (1,2,6,7). This may be a sign of the effort to keep changes of ICS osmotic load at a minimum. Based on the finding of the exchange of sodium for potassium in the cellular wall, a method has been devised to calculate the UF fraction removed from EC ( UF _EC) expressed as a coefficient K _EC = UF _EC/ UF _ToT, with UF _ToT being the total fluid volume removed during the HD session.     

Calcium exposure and removal in chronic hemodialysis patients.

The risks associated with calcium exposure in chronic hemodialysis (HD) patients are becoming increasingly apparent. Current K/DOQI guidelines recommend an absolute maximum elemental calcium load of 2,000 mg/d, including calcium-containing medication and a maximum dialysate calcium concentration of 1.25 mmol/L (to avoid intradialytic calcium loading). The goal of this study was to characterize the total exposure to calcium from all sources that chronic HD patients are exposed to. We studied 52 patients. Each was requested to complete a 3-day food diary for analysis of daily calcium intake; 24-hour urine collections were taken and analyzed for calcium content. All patients underwent HD using Hospal Integra (Lyon, France) dialysis monitors, bicarbonate buffering, and dialysate sodium and calcium concentrations of 134 mmol/L and 1.25 mmol/L, respectively. Blood was sampled before and after HD for total serum calcium, albumin, bicarbonate, and phosphate, in addition to ionized calcium level measured at the bedside using a portable electrolyte analyzer. Calcium flux was determined from measurements of ionized calcium levels in dialyzer inlet samples and those in continuous partial waste dialysis collection (with reference to total waste dialysate and ultrafiltration volumes). There was marked interpatient variability of total calcium exposure; the mean was 2,346 +/- 293 mg (range, 230 to 7,309 mg) per day. The majority of enteral calcium exposure was from calcium-containing phosphate binders, with diet providing only a mean load of 581 +/- 34 mg (range, 230 to 1,309 mg). Calcium removal was evident in 83% of patients. Mean calcium flux was -187 +/- 232 mg (range, -486 to 784 mg). There was a linear correlation observed between the amount of calcium removed during dialysis and the predialysis ionized plasma calcium concentration, r2 = 0.42, P < .001 (calculated from actual measured dialysate ionized calcium concentration). This shows that calcium flux across the dialysis membrane is determined by the diffusion gradient. The amount of calcium removed during dialysis was found to be independent of exogenous calcium load. These results support previous reported data showing that the majority of HD patients are continually experiencing calcium overload. This may have a contributory role in the development of vascular calcification. In contrast to recent K/DOQI recommendations, an upper dialysate concentration of 1.25 mmol/L may not be ideal for every patient. To minimize the effects of exogenous calcium overload, dialysate concentrations should be prescribed with reference to plasma calcium levels.     

Impact of convective flow on phosphorus removal in maintenance hemodialysis patients.

OBJECTIVE: Hyperphosphatemia leads to increased risk of death in maintenance hemodialysis patients (MHD). This study investigated phosphorus (P) removal, P reduction rate (PRR), and P rebound, comparing on-line, high-volume hemodiafiltration in postdilution (HDF) and high-flux hemodialysis (HD) in a setting of an equal amount of produced dialysate solution in both modalities. METHODS: A total of 22 MHD patients, treated with regular 3 x 4 hours HDF weekly, were randomly dialyzed with one 4-hour session of HDF and of HD. In both modalities, an equal amount of produced dialysate solution of 800 mL/minute was used. The only variable was the fact that in HDF, 100 mL/min of this produced dialysate solution was used as replacement fluid. The other parameters were kept identical: blood flow rate, 350 mL/min; high-flux polysulfone F80 dialyzer; and 4800 E monitor, (Fresenius, Bad Homburg, Germany). The P removal was measured in total spent dialysate and ultrafiltrate volumes. Statistical analyses were done with the paired t-test. RESULTS: The mean total P removed with HDF was 1159 +/- 296 mg, and 972 +/- 312 mg with HD (P < .001), ie, 19% higher in HDF; PRR was significantly higher in HDF (63.3%) versus HD (58.6%) (P = .014). The mean serum P did not differ: 5.3 mg/dL in HDF and 5.2 mg/dL in HD. There was a linear correlation between serum P and P removal. With a serum P level up to 5 to 5.5 mg/dL, HDF achieved a higher P removal compared with HD. The difference gradually decreased as the serum P value increased. Above 7 mg/dL, no difference in total P removal was observed. There was a high but equal rebound percentage at 60 minutes in HDF (42%) and HD (39%) (P = .42). With HDF, no predialysis metabolic acidosis was noted. CONCLUSIONS: Treatment with on-line HDF in postdilution resulted in a higher P removal and higher PRR compared with HD. The long-term implementation of this modality may result in a more optimal serum P control, without an increase in the number of or lengthening of the dialysis sessions.     

Pharmacokinetics of netilmicin in hypertonic hemodiafiltration and standard hemodialysis

Recently, we developed a peculiar model of hemodiafiltration (HDF), in which a conventional acetate hemodialysis (HD) is combined with a high flux dialyzer, a high ultrafiltration flow rate and a postdilution hypertonic reinfusion (H HDF). The pharmacokinetics of netilmicin (N), a relatively new aminoglycoside, were evaluated during 5 sessions of H HDF of 180 min and 2 sessions of HD of 270 min in the same 8 patients with a comparable blood (approximately 400 ml/min) and dialysate flow rate (approximately 520 ml/min). Additional studies were performed in 7 out of the 8 patients after 2 sessions of H HDF and one session of HD. N clearance, calculated both as plasma water and total body clearance, was so exceedingly higher during H HDF than during HD, that the amount of drug removed by H HDF in 180 min was still significantly higher than that removed by HD in 270 min. Consequently, the N half-life during HD was about 5 h, whereas during H HDF it was less than 2.5 h, approaching that reported in normal subjects. N half-life out of dialysis treatments was about 55 h. In conclusion, N pharmacokinetics are strikingly different between H HDF and HD, with N clearance during H HDF about the double of that during HD. The implications of this study are: a different dosage adjustment of aminoglycosides is needed for patients routinely treated by HDF; HDF may be a very effective treatment for the overdose of many drugs.