Chronic fluid overload has been related to severely increased mortality in ESRD patients. In addition, the increasing prevalence of diabetes along with concomitant diseases make fluid management more difficult and calls for individualized fluid targets, taking co-morbidities into account. Aim of this work was to assess the mortality risk of diabetes in different degrees of chronic fluid overload, and to identify potential target ranges for optimal outcome.

Introduction and Aims: Peginesatide is a once-monthly, peptide-based erythropoiesis-stimulating agent (ESA) approved in the US for treatment of anemia due to chronic kidney disease (CKD) in adult patients ( pts) on dialysis.Peginesatide demonstrated noninferiority to epoetin in maintaining hemoglobin (Hb) in hemodialysis (HD) pts in two Phase 3 randomized trials (EMERALD 1, 2; Fishbane et al.NEJM 2013).Time to dose stability with a less frequently administered ESA is an issue of clinical interest.This post-hoc analysis evaluated the time to achieve initial dose stability in pts who converted from stable epoetin to peginesatide, or maintenance of dose stability in pts who remained on epoetin.Methods: Data were pooled from the EMERALD trials assessing safety and efficacy of peginesatide (Q4W; n=1066) vs epoetin alfa/beta (1-3x weekly; n=542) in HD pts previously on stable epoetin.Dose adjustments were to be made no more than once Q4W (unless for safety reasons) to maintain Hb 10-12 g/dL ( per guidelines in effect at time of trial).Hb was measured Q2W (or QW during evaluation period [Wk 29-36] and dose postponements).Due to different dosing frequencies, definitions of dose stability were different between treatments: (1) subsequent dose changed by <20% of prior dose, with 21-35d between doses ( peginesatide) or total dose in subsequent month changed by <20% of prior month's total dose (epoetin); and (2) at least 1 Hb was within target between doses ( peginesatide) or between first dose of consecutive months (epoetin).The evaluable population were pts who received ≥2 peginesatide doses (n=1034) or ≥2 months of epoetin (n=528).Results: Similar proportions (96.6%) of pts achieved ( peginesatide) or maintained (epoetin) dose stability.For peginesatide and epoetin, respectively, dose stability was achieved or maintained after: 1st dose in 61.4% and 54.9%, 2nd dose in 76.7% and 67.4%, and 3rd dose in 84.9% and 77.2% of pts.The most common reason for not achieving peginesatide initial dose stability at 1st dose was a ≥20% decrease in the 2nd dose.Both groups achieved or maintained dose stability at similar rates (in wks; Fig) .Conclusions: After conversion from stable epoetin, >75% of peginesatide pts achieved initial dose stability within 1-2 doses.Compared with pts who remained on epoetin, peginesatide pts did not differ in achievement of dose stability.These post-hoc results may warrant further study.

The measurement of relative blood volume (RBV) changes during ultrafiltration assume a constant mass and distribution of circulating blood components such as hematocrit. The authors examine the validity of this assumption in 10 subjects undergoing repeated direct measurements of systemic hematocrit and plasma volume (PV(icg)) using indocyanine green dilution at four stages of dialysis with intermittent ultrafiltration. Ultrasonic RBV changes were monitored. Absolute blood volumes (ABV) were initially derived for each PV(icg) estimate, and corresponding measured systemic hematocrit was adjusted by a factor of 0.86 to correct for the difference between the systemic and whole-body hematocrit (constant Fcell ratio). PV(icg) and ABV changes correlated closely (R = 0.98; P <0.001). ABV changes overestimated reduction in PV(icg) during ultrafiltration (mean difference, -140 +/- 202 ml). The calculated red cell mass however was variable (P <0.01). Fcell ratio was then adjusted at each blood volume measurement (Fcell(1), 0.87 +/- 0.02; Fcell(2), 0.89 +/- 0.03; Fcell(3), 0.94 +/- 0.06; Fcell(4), 0.94 +/- 0.04; P <0.01) to maintain a constant red cell mass (2146 +/- 460 ml). When ABV was recalculated using PV(icg), systemic hematocrit and variable Fcell (ABV(Fvariable)), the mean difference between PV(icg) changes and ABV(Fvariable) changes, was negligible (-0.2 +/- 35 ml). During intermittent ultrafiltration, RBV changes systematically underestimated the percentage reduction in ABV (mean difference, 7.7 +/- 10.6%). When corrected for variations in Fcell, ABV(Fvariable) and RBV differences were negligible (mean difference 1.2 +/- 2.6%). Varying Fcell ratio probably reflects microvascular volume change with net fluid shift from the microcirculation to macrocirculation (intravascular refill). This may result in underestimation of changes in systemic hematocrit and RBV during dialysis such that they were less than those predicted by directly measured changes in plasma volume.

A method for determining at least one of a component poor hydration, a component of adipose tissue component and a lean tissue of a patient, comprising the steps of: determining chemical or physical properties of the patient and deriving the at least one component based on the chemical or physical properties and previously determined fraction of a certain mass or volume of water in lean tissue and a mass or volume fraction of water in adipose tissue values.

Hemodynamic stability during hemodialysis depends largely on plasma volume (PV) preservation during ultrafiltration (UF). Current estimates of blood volume (BV) are indirect or involve the use of radioactive tracers, which does not allow repeated measurements during hemodialysis. Indocyanine green was used to measure PV during hemodialysis. After an initial pilot phase (phase I), PV values were determined before dialysis, repeatedly during isovolemic hemodialysis (phase II), and during stepwise UF (phase III). Absolute BV values were calculated from PV and hematocrit values. Patients were monitored for extracellular fluid volume (bioimpedance monitoring) and relative BV changes (ultrasonic monitoring). Phase I demonstrated dye stability in plasma, peak absorbance at 805 nm, and a short half-life (4.53 +/- 1.5 min). Ten milligrams of dye (2.5 mg/ml) were injected for each PV measurement. Eight plasma samples were obtained beginning 3 min after injection, at 1-min intervals, for assessment of decay characteristics. The isovolemic hemodialysis PV measurements demonstrated excellent reproducibility (r(2) = 0.98; method SD, 356 ml; mean coefficient of variation, 4.07%) and a difference of only 149 +/- 341 ml (mean +/- SD), compared with predialysis PV values (Bland-Altman method). PV values at the beginning of dialysis were significantly correlated with body surface area (r(2) = 0.82, P < 0.001) and extracellular fluid estimates (r(2) = 0.73, P < 0.001). BV prediction formulae significantly underestimated absolute BV at the start of dialysis (P < 0.0001). The findings demonstrate that this method can be used for repeated PV determinations during hemodialysis, with excellent reproducibility. It is a potential tool for further research on hemodynamic stability during UF.

BACKGROUND Relative blood volume (RBV) changes during hemodialysis (HD) are poorly understood. We wish to define characteristics of RBV profiles at different hydration states predictive of hemodynamic instability. METHODS Thirty patients underwent online RBV monitoring during an HD session with intermittent ultrafiltration (UF) pulses administered until the onset of hypotension. The RBV decay constant (tau) was derived from curve fitting. Linear divergence, the net deviation of the RBV curve during UF from predicted linear decay, was computed from initial 1-minute slopes. RESULTS The best correlation with proximity to dry weight (PDW) was provided by linear divergence (r = 0.817; P < 0.001), its major determinant in multiple regression analysis. Other predictors were RBV at initiation of UF pulse, UF pulse volume, and UF decay constant (tau(UF)). These parameters were significantly different in UF pulses within 1 kg and 1 kg or greater of dry weight. There were no correlations with refill parameters. The occurrence of hypotension was not different at RBVs less than 90% (7.4%) or 90% or greater (5.3%). tau(UF), linear divergence, RBV at initiation of UF pulse (all P < 0.001), and UF decay amplitude (P < 0.01) were different between hypotensive and normotensive UF pulses. Hypotension was the only independent predictor of tau(UF) (R2 = 0.40; P < 0.001). The only independent predictor of linear divergence was PDW (R2 = 0.667; P < 0.001). CONCLUSION Approaching dry weight, the RBV decline during UF switched from exponential to linear decay, probably indicating failing vascular refill. Monitoring deviation from linearity may allow improved hemodynamic stability and attainment of optimal post-HD weight.

In patients with kidney failure, it is necessary to remove ingested fluid during a dialysis treatment. This paper describes the development of a compartmental fluid kinetic model for the interpretation of blood volume changes that occur when fluid is removed during a dialysis treatment. Fluid transfer between compartments may be assisted by active refilling, a process which has been taken into account in the model and is in agreement with findings from clinical studies. This model could form the basis of control algorithms for fluid control during dialysis.

Blood pressure instability is the most frequent complication of haemodialysis treatments, Individualised control of fluid removal that takes into account impaired physiological responses, is the key to improved stability. The cardiopulmonary reflex, the first line of defence to prevent hypotension caused by hypovolaemia, is mainly dependant on the central venous pressure (CVP). Until now only invasive methods are available for the measurement of CVP. A system for observing the venous pressure based on cardiac output, blood pressure and heart rate measurements combined with additional information about the patients heart condition (hypertrophy and contractility) was developed, The core of this system is an inverted non-pulsatile model of the heart which enables the reconstruction of the venous pressure. A cross cheek of the calculated venous pressure values by using relative blood volume measurements was applied to 12 different patients. The reconstructed venous pressure is linearly volume dependent and stays inside the known physiological range. It decreases during the dialysis treatment from very high values (12 mmHg) in the heavily fluid overloaded stage, towards near normal values (3 mmHg) when reaching dry weight. The results are reproducible and patient specific. The venous pressure can be used as a much better indicator for oncoming hypotension episodes then the mean arterial pressure

Blood pressure instability is the most frequent complication of haemodia-lysis treatments. Individualised control of fluid removal, taking into account impaired physiological responses, is the key to improved stability. Heart rate and the function of the arterial vessels can be identified using a two model approach. An inverted heart model has been used to estimate venous pressure from cardiac output. A model of the closed circulatory system has facilitated the analysis of arterial and venous resistance in 12 patients. Both resistances were found to increase, reaching physiological levels only after heavy fluid reduction.

In this paper a method for identifying and classifying hemodialysis patients based on the relative blood volume (RBV) is presented. A group of 42 hemodialysis patients were treated with a special ultrafiltration pattern. The response in RBV to this pattern was recorded and analysed. Using the steady state and time constant of a fitted and estimated function, the patients can clearly be separated into 4 different groups. The analysed parameters give information about the fluid-status, the hemodynamic stability and the physiologic and pathologic patient conditions

Immediately after hemodialysis, the urea concentration rebounds upwards as urea continues to be transferred into the arterial circulation from peripheral body compartments. This rebound takes at least 30 minutes to complete. Hemodialysis is quantified as the Kt/V, calculated prom pre- and post-dialysis urea samples. Unless the post-dialysis sample is taken at least 30 minutes after dialysis, the Kt/V will be overestimated. This overestimation will be relatively greater in short high-efficiency dialyses, which have greater post-dialysis rebounds. We propose a method of correction that uses only the conventional pre- and immediate post-dialysis samples and is based on the physiologically-appropriate patient clearance time (tp). This is the time needed to clear all body compartments when the dialyzer clearance is infinite. The tp can be calculated from the pre-, immediate post- and 30-minute post-dialysis urea concentrations and was 35 minutes (SD 16) in 29 patients undergoing short (149 min) hemodiafiltration and standard (243 min) hemodialysis the following week. There was no significant difference between tp values calculated during the two treatments. Standard Kt/V can be corrected by multiplying by t/(t + tp) and dialysis time should be increased by tp x Kt/V minutes to compensate for the rebound. Despite individual variations in tp, a value of tp = 35 was sufficient to correct Kt/V in all patients. Kt/V corrected in this way agreed with Kt/V calculated using a 60-minute post-dialysis sample (r = 0.856, P < 0.001). The method predicted the 60-minute post-rebound concentration (SE 0.5 mM, r = 0.983, P < 0.001) and the addition of 35 minutes to the treatment time corrected for the rebound in both conventional and short treatments. Similar simple equations corrected the error in V caused by rebound effects.

Limitations to short haemodiaiysis It is now generally accepted that there is a significant risk of underdialysis if the treatment time is shortened towards 4 h or less. To avoid these risks, a return to longer dialysis times has been advocated, despite the increase in cost and inconvenience to the patient. An alternative strategy would be to understand the mechanism of reduced efficiency in short dialysis and specifically correct for it without resorting to long treatments. If it were possible to increase the rate of removal of fluid and solute mass in proportion to the reduction of dialysis time, without increasing the patient's fluid content, blood pressure or solute concentrations, then the short treatment would have equivalent efficacy to the long treatment. There are a number of factors which combine to reduce rate of fluid and solute removal in short dialysis. These include the relatively slow diffusion of middle and large molecular weight solutes, hypotension related to high ultrafiltration rates and the post-dialysis rebound. This paper will consider only the post-dialysis rebound, although it is accepted that other factors need to be considered when prescribing short dialysis. The rate at which solute can be removed from the patient is dependent on the dialyser clearance and on the rate at which solute can be conveyed from all parts of the body into the arterial needle. While the dialyser clearance rate is controllable and relatively easy to measure, the other factors are much more difficult to measure and are generally impossible to modify. For solute to travel from the intracellular compartment (which is the largest body water compartment) to the needle, it must cross the cell membrane, be carried into the central circulation by venous blood flow, be pumped into the aorta by the heart and carried to the needle by the fistula blood flow. Therefore the rate of transfer depends on the intra/extracellular mass transfer coefficient, regional blood flow rates, cardiac output