Fabio Grandi

Electrophysiological response to dialysis: the role of dialysate potassium content and profiling.

UNLABELLED The task of dialysis therapy is, amongst other things, to remove excess potassium (K+) from the body. The need to achieve an adequate K+ removal with the risk of cardiac arrhythmias due to sudden intra-extracellular K+ gradient advises the distribution of the removal throughout the dialysis session instead of just in the first half. The aim of the study was to investigate the electrical behavior of two different K+ removal rates on myocardial cells (risk of arrhythmia and ECG alterations). Constant acetate-free biofiltration (AFB) and profiled K+ (decreasing during the treatment) AFB (AFBK) were used in a patient sample to understand, first of all, the effect on premature ventricular contraction (PVC) and on repolarization indices [QT dispersion (QTd) and principal component analysis (PCA)]. The study was divided into two phases: phase 1 was a pilot study to evaluate K+ kinetics and to test the effect on the electrophysiological response of the two procedures. The second phase was set up as an extended cross-over multicenter trial in patient subsets prone to arrhythmias during dialysis. Phase 1: PVC increased during both AFB and AFBK but less in the latter in the middle of dialysis (298 in AFB vs. 200 in AFBK). The PVC/h in a subset of arrhythmic patients was 404 +/- 145 in AFB and 309 +/- 116 in AFBK (p = 0.0028). QT interval (QTc) prolongation was less pronounced in AFBK than in AFB. Phase 2: The PVC again increased in both AFB and AFBK but less in the latter mid-way through dialysis (79 +/- 19 AFB vs. 53 +/- 13 AFBK). Moreover, in the most arrhythmic patients the benefit accruing from the smooth K+ removal rate was more pronounced (103 +/- 19 in AFB vs. 78 +/- 13 in AFBK). CONCLUSION It is not the K+ dialysis removal alone that can be destabilizing from an electrophysiological standpoint, but rather its removal dynamics. This is all the more evident in patients with arrhythmias who benefit from the K+ profiling during their dialysis treatment.

Model-Based Analysis of Potassium Removal During Hemodialysis

Potassium ion (K(+)) kinetics in intra- and extracellular compartments during dialysis was studied by means of a double-pool computer model, which included potassium-dependent active transport (Na-K-ATPase pump) in 38 patients undergoing chronic hemodialysis. Each patient was treated for 2 weeks with a constant K(+) dialysate concentration (K(+)(CONST) therapy) and afterward for 2 weeks with a time-varying (profiled) K(+) dialysate concentration (K(+)(PROF) therapy). The two therapies induced different levels of K(+) plasma concentration (K(+)(CONST): 3.71 +/- 0.88 mmol/L vs. K(+)(PROF): 3.97 +/- 0.64 mmol/L, time-averaged values, P < 0.01). The computer model was tuned to accurately fit plasmatic K(+) measured in the course and 1 h after K(+)(CONST) and K(+)(PROF) therapies and was then used to simulate the kinetics of intra- and extracellular K(+). Model-based analysis showed that almost all the K(+) removal in the first 90 min of dialysis was derived from the extracellular compartment. The different K(+) time course in the dialysate and the consequently different Na-K pump activity resulted in a different sharing of removed potassium mass at the end of dialysis: 56% +/- 17% from the extracellular compartment in K(+)(PROF) versus 41% +/- 14% in K(+)(CONST). At the end of both therapies, the K(+) distribution was largely unbalanced, and, in the next 3 h, K(+) continued to flow in the extracellular space (about 24 mmol). After rebalancing, about 80% of the K(+) mass that was removed derived from the intracellular compartment. In conclusion, the Na-K pump plays a major role in K(+) apportionment between extracellular and intracellular compartments, and potassium dialysate concentration strongly influences pump activity.

Acetate-Free Biofiltration

Acetate-free biofiltration (AFB) is a hemodiafiltration technique that, technically as well as biologically speaking, has all the premises for being a perfectly biocompatible technique capable of satisfying even the demands of critical patients laden with comorbidities. Important clinical benefits to patients have been reported, such as a better correction of acid-base balance, an improved nutritional status and a better hemodynamic stability. In particular, as far as the cardiovascular instability is concerned, several studies have shown that the rationale behind a better hemodynamic stability is the overall absence of acetate usually present in the dialysis bath, which often leads to an impaired vascular tone and a reduced cardiac contractility. One of the powerful features of AFB is its adaptability to new devices and tools which can be easily and safely used. In AFB, potassium modulation in the dialysate is easily achieved. Thus, patients with elevated levels of predialysis potassium and a tendency to develop both intra- and interdialysis arrhythmias benefit most. Lastly, the possibility to associate AFB with devices like Hemocontrol (which allows for a feedback conditioning of blood volume) broadens its practical scope, not only for use with hypotension-prone patients, but also with hypertensive patients with massive increases in their interdialysis body weight. In this category of patients, avoiding the risk of dangerous hypovolemias allows for the achievement of dry body weight, thereby facilitating the control of arterial blood pressure and minimizing the clinical consequences of a chronic fluid overload.

Adsorption in Extracorporeal Blood Purification: How to Enhance Solutes Removal Beyond Diffusion and Convection

Uremic syndrome is linked to a plethora of uremic toxins circulating in the body in ESRD patients. Their overall spectrum is partly or entirely unexplored despite the need to urgently define the specimens and the patho-physiology beyond their high blood levels to address new or more selective removal strategies. It is generally accepted that convective hemodialysis is the best choice to remove large part of the molecular spectrum, even though it is not fully demonstrated its superiority in terms of clinical outcomes. Then, transport mechanisms can benefit from maximizing all the physi‐ co-chemical principles including diffusion for small solutes, convection for middle mole‐ cules and adsorption for large molecular size uremic toxins. The latter has not been fully adopted in hemodialysis and this transport mechanisms is limited to the intrinsic capability of dialysis membrane to adsorb macromolecules while transporting solutes by diffusion and/or convection. However, poorly has been explored about the use of sorbents to enhance the solute removal in hemodialysis. The purpose of this chapter is to summarize the main contributions of so far published clini‐ cal and technical experiences. The chapter will be structured as follow: first we introduced a summary of the basic princi‐ ples of solutes transport and relative contribution of the different mechanisms to the overall