Changing paradigms of renal replacement therapy in chronic kidney disease patients: ultrapure dialysis fluid and high-efficiency hemodiafiltration for all?

Ultrapurity of dialysis fluid is important for the biocompatibility of renal replacement therapy systems. Penne and collaborators have assessed the microbiological quality of water and dialysis fluid in dialysis facilities. No side effects were noted in 97 patients who received 11,258 online hemodiafiltration sessions. This study confirms that ultrapure water and dialysis fluid may be easily produced and used for online hemodiafiltration

Principles of Haemodiafiltration: Rationale for Improved Patients’ Survival

Haemodiafiltration (HDF) is a renal replacement modality that combines diffusion and enhanced convection in order to remove small- and middle-molecular-weight compounds, respectively. They are removed along solvent drag effect of ultrafiltration through increased transmembrane pressure (TMP), whereas the replacement solution is infused intravenously at equal amount minus the desired fluid volume removal for achieving dry weight. Limiting factors for high-volume on-line haemodiafiltration (HV oHDF) are blood flow and viscosity (haematocrit, protocrit), filter performance and technical features of HDF monitor. Most recent advanced technology of dynamic analysis of pressure pulses along the blood flow pathway in the dialyser has enabled optimal ultrafiltration flow performances. HV oHDF offers today the best compromise of cardioprotective option by reducing cardiovascular risk factors in end-stage kidney disease patients. Recent randomised controlled trials (RCTs), individual participant data meta-analyses and a number of observational studies have shown the evidence of survival advantage of HDF over conventional haemodialysis (HD). The convective volume has become the key quantifier for HV oHDF as the measure of dialysis dose. Its cut-off values for better survival have been recognised, but the research is still needed in the years to come to set the required optimal volumes tailored to individual patients’ needs

Update on Clinical Evidence Supporting Hemodiafiltration

The aim of this chapter is to define hemodiafiltration target efficiency, to clarify the concept of “optimal convective dose,” and to facilitate hemodiafiltration (HDF) implementation in clinical practice by addressing the need for the establishment of best clinical practices for HDF. The approach taken was to conduct a comprehensive summary of clinical evidence supporting HDF. Convective dose is the total ultrafiltered volume and is complementary to diffusive dose (urea Kt/V) as a dose‐dependent parameter. It can be quantified and adjusted to patient characteristics. Factors affecting convective dose are discussed: patient characteristics, prescription‐dependent factors, and technical and machine‐dependent factors. The key issue of HDF prescription and implementation of best practices is addressed as are intermediary and endpoint clinical outcomes. The main messages are as follows: (1) HDF is safe and effective provided that best clinical practices are followed and the right convective dose is delivered; (2) HDF is easy to perform with new technology; and (3) depending on the convection volume, HDF reduces all‐cause and cardiovascular mortality. Open challenges remain, namely, the implementation of best practices to (a) achieve optimal convection volume, (b) define patient subsets that would benefit more from HDF, and (c) evaluate new tools that fine‐tune HDF prescription according to individual patient needs

Controversy on the CONVINCE study findings: the PRO take

The CONVINCE study, recently published in the New England Journal of Medicine, reveals a groundbreaking 23% reduction in the relative risk of all-cause mortality among end-stage kidney patients undergoing high convective volume hemodiafiltration. This significant finding challenges the conventional use of high-flux hemodialysis and offers hope for improving outcomes in chronic kidney disease patients. While some controversies surround the study's findings, including concerns about generalizability and the causes of death, it is essential to acknowledge the study's design and its main outcomes. The CONVINCE study, part of the HORIZON 2020 project, enrolled 1360 patients and demonstrated the superiority of hemodiafiltration in reducing all-cause mortality overall, as well as in specific patient subgroups (elderly, short vintage, non-diabetic, and those without cardiac issues). Interestingly, it was shown that hemodiafiltration had a protective effect against infection, including COVID-19. Future research will address sustainability, dose scaling effects, identification of subgroups especially likely to benefit and cost-effectiveness. However, for now, the findings strongly support a broader adoption of hemodiafiltration in renal replacement therapy, marking a significant advancement in the field

Oxidative stress in hemodialysis patients: Is NADPH oxidase complex the culprit?

Oxidative stress in hemodialysis patients: Is NADPH oxidase complex the culprit?Oxidative stress results from an imbalance between oxidant production, including reactive oxygen species (ROS), reactive nitrogen species (RNS), chlorinated compounds, and antioxidant defense mechanisms. Most reports prove that oxidative stress is present in ESRD patients. Several studies tend to accreditate the hypothesis by which oxidative stress is a strong co-factor for the development of complications related to long-term HD such as atherosclerosis, amyloidosis, malnutrition, anemia, and infection.In order to evaluate the rationale for curative action against oxidative damage in chronic renal failure patients, we reviewed the putative factors involved in this process. Antioxidant systems are severely impaired in uremic patients and gradually altered with the degree of renal failure. Moreover, the inflammatory state caused by the hemoincompatibility of the dialysis system plays a critical role in the activation of NADPH oxidase, aggravating the pro-oxidant status of uremic patients.Prevention of ROS overproduction by improvement of dialysis biocompatibility, an important component of adequate dialysis, might be completed by antioxidant supplementation

Vascular Access Management for Haemodialysis: A Value-Based Approach from NephroCare Experience

A good functioning vascular access (VA) is a prerequisite to obtain a successful dialysis treatment. This chapter reviews VA management in advanced chronic kidney disease (CKD) patients drawn from the experience of a large network dialysis care provider with the following sections: overview on VA management in advanced CKD that follows patient pathway and patient profile, current practice patterns in line with best clinical practices; VA creation addressing crucial themes: when and what type of VA to construct, how to assess patient pre-emptively, how to proceed for the construction and monitoring to prevent early failures and complications; VA management with particular focus on clinical monitoring, surveillance and interventional procedures required to preserve patency and functionality of VA; the often-forgotten patient perspective is VA usage. What information to share, how to proceed for preventing pain, and fears related with VA needling? What should patients know about their VA and how to manage in daily life? Competences, skills and responsibilities of nursing staff when using and managing VA; and future of VA in terms of innovative concept for creating and maintaining VA conduits in dialysis patients

Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results.

Cardiovascular (CV) events are increased 36-fold in patients with end-stage renal disease. However, randomized controlled trials to lower LDL cholesterol (LDL-C) and serum total cholesterol (TC) have not shown significant mortality improvements. An inverse association of TC and LDL-C with all-cause and CV mortality has been observed in patients on chronic dialysis. Lipoproteins also may protect against infectious diseases. We used data from 37,250 patients in the international Monitoring Dialysis Outcomes (MONDO) database to evaluate the association between lipids and infection-related or CV mortality. The study began on the first day of lipid measurement and continued for up to 4 years. We applied Cox proportional models with time-varying covariates to study associations of LDL-C, HDL cholesterol (HDL-C), and triglycerides (TGs) with all-cause, CV, infectious, and other causes of death. Overall, 6,147 patients died (19.2% from CV, 13.2% from infection, and 67.6% from other causes). After multivariable adjustment, higher LDL-C, HDL-C, and TGs were independently associated with lower all-cause death risk. Neither LDL-C nor TGs were associated with CV death, and HDL-C was associated with lower CV risk. Higher LDL-C and HDL-C were associated with a lower risk of death from infection or other non-CV causes. LDL-C was associated with reduced all-cause and infectious, but not CV mortality, which resulted in the inverse association with all-cause mortality

Intradialytic cardiac magnetic resonance imaging to assess cardiovascular responses in a short-term trial of hemodiafiltration and hemodialysis

Hemodynamic stress during hemodialysis (HD) results in recurrent segmental ischemic injury (myocardial stunning) that drives cumulative cardiac damage. We performed a fully comprehensive study of the cardiovascular effect of dialysis sessions using intradialytic cardiac magnetic resonance imaging (MRI) to examine the comparative acute effects of standard HD versus hemodiafiltration (HDF) in stable patients. We randomly allocated 12 patients on HD (ages 32–72 years old) to either HD or HDF. Patients were stabilized on a modality for 2 weeks before undergoing serial cardiac MRI assessment during dialysis. Patients then crossed over to the other modality and were rescanned after 2 weeks. Cardiac MRI measurements included cardiac index, stroke volume index, global and regional contractile function (myocardial strain), coronary artery flow, andmyocardial perfusion. Patients had mean6SEMultrafiltration rates of 3.862.9 ml/kg per hour during HD and 4.462.5 ml/kg per hour during HDF (P=0.29), and both modalities provided a similar degree of cooling. All measures of systolic contractile function fell during HD and HDF, with partial recovery after dialysis. All patients experienced some degree of segmental left ventricular dysfunction, with severity proportional to ultrafiltration rate and BP reduction. Myocardial perfusion decreased significantly during HD and HDF. Treatment modality did not influence any of the cardiovascular responses to dialysis. In conclusion, in this randomized, crossover study, there was no significant difference in the cardiovascular response to HDF or HD with cooled dialysate as assessed with intradialytic MRI