Hemodialysis and peritoneal dialysis

The extent of removal of the uremic toxins in hemodialysis (HD) therapies depends primarily on the dialysis membrane characteristics and the solute transport mechanisms involved. While designation of ‘flux’ of membranes as well toxicity of compounds that need to be targeted for removal remain unresolved issues, the relative role, efficiency and utilization of solute removal principles to optimize HD treatment are better delineated. Through the combination and intensity of diffusive and convective removal forces, levels of concentrations of a broad spectrum of uremic toxins can be lowered significantly and successfully. Extended clinical experience as well as data from several clinical trials attest to the benefits of convection-based HD treatment modalities. However, the mode of delivery of HD can further enhance the effectiveness of therapies. Other than treatment time, frequency and location that offer clinical benefits and increase patient well-being, treatment- and patient-specific criteria may be tailored for the therapy delivered: electrolytic composition, dialysate buffer and concentration and choice of anticoagulating agent are crucial for dialysis tolerance and efficacy. Evidence-based medicine (EBM) relies on three tenets, i.e. clinical expertise (i.e. doctor), patient-centered values (i.e. patient) and relevant scientific evidence (i.e. science), that have deviated from their initial aim and summarized to scientific evidence, leading to tyranny of randomized controlled trials. One must recognize that practice patterns as shown by Dialysis Outcomes and Practice Patterns Study and personalization of HD care are the main driving force for improving outcomes. Based on a combination of the three pillars of EBM, and particularly on bedside patient–clinician interaction, we summarize what we have learned over the last 6 decades in terms of best practices to improve outcomes in HD patients. Management of initiation of dialysis, vascular access, preservation of kidney function, selection of biocompatible dialysers and use of dialysis fluids of high microbiological purity to restrict inflammation are just some of the approaches where clinical experience is vital in the absence of definitive scientific evidence. Further, HD adequacy needs to be considered as a broad and multitarget approach covering not just the dose of dialysis provided, but meeting individual patient needs (e.g. fluid volume, acid–base, blood pressure, bone disease metabolism control) through regular assessment—and adjustment—of a series of indicators of treatment efficiency. Finally, in whichever way new technologies (i.e. artificial intelligence, connected health) are embraced in the future to improve the delivery of dialysis, the human dimension of the patient–doctor interaction is irreplaceable. Kidney medicine should remain ‘an art’ and will never be just ‘a science’.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Choices in hemodialysis therapies: variants, personalized therapy and application of evidence-based medicine

Canaud

Stuard

Laukhuf

et al. 2021

“…A crucial but lesser degree of transport in the opposite direction is necessary to replenish the blood with electrolytes depleted during dialysis and to correct metabolic acidosis with buffers to control acid–base derangements. Understanding and accomplishing a higher degree of control of transport in both directions is the central objective of delivery of dialysis that determines its efficacy and tolerance, as well as outcomes [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical relevance of abstruse transport phenomena in haemodialysis

Bowry¹,

Kırçelli

Mooppil³

et al. 2021

Haemodialysis (HD) utilizes the bidirectional properties of semipermeable membranes to remove uraemic toxins from blood while simultaneously replenishing electrolytes and buffers to correct metabolic acidosis. However, the nonspecific size-dependent transport across membranes also means that certain useful plasma constituents may be removed from the patient (together with uraemic toxins), or toxic compounds, e.g. endotoxin fragments, may accompany electrolytes and buffers of the dialysis fluids into blood and elicit severe biological reactions. We describe the mechanisms and implications of these undesirable transport processes that are inherent to all HD therapies and propose approaches to mitigate the effects of such transport. We focus particularly on two undesirable events that are considered to adversely affect HD therapy and possibly impact patient outcomes. Firstly, we describe how loss of albumin (and other essential substances) can occur while striving to eliminate larger uraemic toxins during HD and why hypoalbuminemia is a clinical condition to contend with. Secondly, we describe the origins and mode of transport of biologically active substances (from dialysis fluids with bacterial contamination) into the blood compartment and biological reactions they elicit. Endotoxin fragments activate various proinflammatory pathways to increase the underlying inflammation associated with chronic kidney disease. Both phenomena involve the physical as well as chemical properties of membranes that must be selected judiciously to balance the benefits with potential risks patients may encounter, in both the short and long term.

Flummoxed by flux: the indeterminate principles of haemodialysis

Bowry¹,

Kırçelli

Misra

2021

In haemodialysis (HD), unwanted substances (uraemic retention solutes or ‘uraemic toxins’) that accumulate in uraemia are removed from blood by transport across the semipermeable membrane. Like all membrane separation processes, the transport requires driving forces to facilitate the transfer of molecules across the membrane. The magnitude of the transport is quantified by the phenomenon of ‘flux’, a finite parameter defined as the volume of fluid (or permeate) transferred per unit area of membrane surface per unit time. In HD, as transmembrane pressure is applied to facilitate fluid flow or flux across the membrane to enhance solute removal, flux is defined by the ultrafiltration coefficient (KUF; mL/h/mmHg) reflecting the hydraulic permeability of the membrane. However, in HD, the designation of flux has come to be used in a much broader sense and the term is commonly used interchangeably and erroneously with other measures of membrane separation processes, resulting in considerable confusion. Increased flux is perceived to reflect more ‘porous’ membranes having ‘larger’ pores, even though other membrane and therapy attributes determine the magnitude of flux achieved during HD. Adjectival designations of flux (low-, mid-, high-, super-, ultra-) have found indiscriminate usage in the scientific literature to qualify a parameter that influences clinical decision making and prescription of therapy modalities (low-flux or high-flux HD). Over the years the concept and definition of flux has undergone arbitrary and periodic adjustment and redefinition by authors in publications, regulatory bodies (US Food and Drug Administration) and professional association guidelines (European Renal Association, Kidney Disease Outcomes Quality Initiative), with little consensus. Industry has stretched the boundaries of flux to derive marketing advantages, justify increased reimbursement or contrive new classes of therapy modalities when in fact flux is just one of several specifications that determine membrane or dialyser performance. Membranes considered as high-flux previously are today at the lower end of the flux spectrum. Further, additional parameters unrelated to the rate of diffusive or convective transport (flux) are used in conjunction with or in place of KUF to allude to flux: clearance (mL/min, e.g. of β2-microglobulin) or sieving coefficients (dimensionless). Considering that clinical trials in nephrology, designed to make therapy recommendations and guide policy with economic repercussions, are based on the parameter flux they merit clarification—by regulatory authorities and scientists alike—to avoid further misappropriation.