Modification of Dialysate Na+ Concentration but not Ultrafiltration or Dialysis Treatment Time Affects Tissue Na+ Deposition in Patients on Hemodialysis.

Introduction: Tissue Na+ overload is present in patients receiving hemodialysis (HD) and is associated with cardiovascular mortality. Strategies to actively modify tissue Na+ amount in these patients by adjusting the HD regimen have not been evaluated. Methods: In several substudies, including cross-sectional analyses (n = 75 patients on HD), a cohort study and a cross-over interventional study (n = 10 patients each), we assessed the impact of ultrafiltration (UF) volume, prolongation of dialysis treatment time, and modification of dialysate Na+ concentration on tissue Na+ content using 23Na magnetic resonance imaging (23Na-MRI). Results: In the cross-sectional analysis of our patients on HD, differences in dialysate sodium concentration ([Na+]) were associated with changes in tissue Na+ content, whereas neither UF volume nor HD treatment time affected tissue Na+ amount. Skin Na+ content was lower in 17 patients on HD, with dialysate [Na+] of <138 mmol/l compared to 58 patients dialyzing at ≥138 mmol/l (20.7 ± 7.3 vs. 26.0 ± 8.8 arbitrary units [a.u.], P < 0.05). In the cohort study, intraindividual prolongation of HD treatment time was not associated with a reduction in tissue Na+ content. Corresponding to the observational data, intraindividual modification of dialysate [Na+] from 138 to 142 to 135 mmol/l resulted in concordant changes in skin Na+ (24.3 ± 7.6 vs. 26.3 ± 8.0 vs. 20.8 ± 5.6 a.u, P < 0.05 each), whereas no significant change in muscle Na+ occurred. Conclusion: Solely adjustment of dialysate [Na+] had a reproducible impact on tissue Na+ content. 23Na-MRI could be utilized to monitor the effectiveness of dialysate [Na+] modifications in randomized-controlled outcome trials.

Cardiovascular calcifications in dialysis patients / Calcifications cardiovasculaires chez le patient dialysé

Patients with advanced chronic kidney disease and those already on dialysis have an increased prevalence of cardiovascular calcifications. They are the cause of severe complications and are associated with a reduced life expectancy in these patients. Recommendations and imaging scores have been developed to detect and assess their importance, to guide and improve the management of cardiovascular risk. However, despite these recommendations, current practice teaches us that they are only partially applied. The prevention and treatment of cardiovascular calcifications go through the correction of classic risk factors associated with atherosclerosis, mineral and bone metabolism disorders and by optimizing the dose and the efficiency of dialysis. New therapeutic strategies are beginning to emerge, others are being evaluated, such as sodium thiosulfate, rheopheresis, vitamin K, magnesium supplementation, and SNF-472.

Les patients atteints de maladie rénale chronique (MRC) avancée et ceux déjà traités par dialyse présentent une prévalence accrue de calcifications cardiovasculaires. Elles sont à l'origine des complications sévères et s'associent à une diminution de l'espérance de vie chez ces patients. Des recommandations et des scores radiographiques ont été développés pour dépister et évaluer leur importance, afin d'orienter et améliorer la prise en charge du risque cardiovasculaire. Cependant, en dépit de ces recommandations, la pratique courante nous enseigne qu'elles ne sont que partiellement appliquées. La prévention et le traitement de calcifications cardiovasculaires passent par la correction des facteurs de risque classiques associés à l'athérosclérose, des troubles du métabolisme minéral et osseux et en optimisant la dose et l'efficacité de la dialyse. Des nouvelles stratégies thérapeutiques commencent à voir le jour, d'autres sont en cours d'évaluation, comme le thiosulfate de sodium, la rhéophérèse, la vitamine K, la supplémentation en magnésium et le SNF-472.

The Green Nephrology Group of the SFNDT: initial reflections / Groupe Néphrologie verte de la SFNDT : premières réflexions

Preserving the environment is becoming a universal priority. Human activities must be redesigned to best adapt them to available resources and to reduce their deleterious impact on the planet. The Green Nephrology Group of the "Société française de néphrologie, dialyse et transplantation" (SFNDT) has started a reflection on these issues, in particular on dialysis, a vital treatment but with high carbon production, associated with high water consumption. The data available on these points are presented such as, among others, the collection of indicators and action plans, the recycling of waste from water treatment, the reduction of dialysate flow, the reuse and regeneration of spent dialysate as well as calculations of carbon emission by dialysis activity. Architectural experiences are reported as well as the regulatory constraints applying to manufacturers and organizations in the sector. Potential solutions require the mobilization of all stakeholders, ranging from patients to health authorities, including caregivers, pharmacists, technicians, nephrologists and facility managers. They will be formalized very soon in a guide being prepared by the SFNDT Green Nephrology Group.

La préservation de l'environnement devient une priorité universelle. Les activités humaines doivent être repensées pour les adapter au mieux aux ressources disponibles et réduire leur impact délétère sur la planète. Le groupe Néphrologie verte de la Société francophone de néphrologie, dialyse et transplantation (SFNDT) a entamé une réflexion sur ces problématiques, en particulier sur la dialyse, traitement à caractère vital mais à production de carbone élevée, associée à une consommation d'eau importante. Les données disponibles sur ces points sont présentées comme, entre autres, le recueil d'indicateurs et les plans d'action, le recyclage du rejet du traitement d'eau, la réduction de débit du dialysat, la réutilisation et régénération du dialysat usé ainsi que les calculs d'émission de carbone par l'activité de dialyse. Les expériences architecturales sont rapportées de même que les contraintes réglementaires s'appliquant aux industriels et établissements du secteur. Les solutions potentielles nécessitent la mobilisation de tous les acteurs, allant des patients aux autorités de santé, en passant par les soignants, pharmaciens, techniciens, néphrologues et les directions d'établissement. Elles seront formalisées très prochainement dans un guide en cours de préparation par le groupe Néphrologie verte de la SFNDT.

Fluid volume management in hemodialysis: never give up!

Every hemodialysis session starts with the question of how much fluid should be removed, which can currently not be answered precisely. Herein, we first revisit the "probing-dry-weight" concept, using the historical example of Tassin/France (practicing also "long, slow dialysis"): Mortality outcomes were, in the 1980s, better than registry data, but are nowadays similar to European average. In view of the negative primary end point in a recent trial on dry weight assessment, based on lung ultrasound-guided evaluation of fluid excess in the lungs, and a meta-analysis of prospective studies failing to show that bioimpedance-based interventions for correction of volume overload had a direct effect on all-cause mortality, we ask how to ever move forward. Clinical reasoning demands that as much information as possible should be gathered on the fluid status of patients undergoing dialysis. Besides body weight and blood pressure, measurements of bioimpedance and dialysate bolus-derived absolute blood volume can in principle be automatized, whereas lung ultrasound can be obtained routinely. In the era of machine learning, fluid management could consist of flexible target weight prescriptions, adjusted on a daily basis and accounting even for fluctuations in fluid-free body mass. In view of all the negative prospective results surrounding fluid management in hemodialysis, we propose this as a "never-give-up" approach.

Vitamin Needs and Treatment for Chronic Kidney Disease Patients.

This paper summarizes the biochemistry, metabolism, and dietary needs of vitamins in patients with chronic kidney disease (CKD) and kidney transplant recipients. Evidence indicates that the dietary intake, in vivo synthesis, urinary excretion or metabolism of different vitamins may be substantially altered in kidney failure. There are discrepancies in vitamin status assessment depending on whether the assay is functional or measuring the blood vitamin level. Whether vitamin supplements should be routinely prescribed for patients with CKD is controversial. Because low dietary intake and compounds that interfere with vitamin activity are not uncommon in patients with CKD, and water-soluble vitamin supplements appear safe and not costly, the authors recommend that supplements of the water-soluble vitamins should be routinely offered to these individuals. More research is needed to assess vitamin nutrition and function and to determine the daily vitamin needs for all patients with CKD.

Nouvelles thérapies dans la prise en charge du patient avec maladie rénale chronique souffrant de prurit : une revue de la littérature New therapies in the management of chronic kidney disease associated pruritus.

Chronic Kidney Disease associated Pruritus (CKD-aP) is a well-established and frequent complication observed in patient with CKD, especially in dialysis patients. However, the management of CKD-aP remains a challenge as the pathophysiology and research studies are too small. Finally, there are a few proposed treatment options with significant clinical benefits. This general review will summarize all the available treatments for the CKD-aP and will highlight the clinical efficacy and limits of the current drugs. Notably, we will focus on the implication of the opioid receptor in the pathophysiology of the CKD-aP and the recently Kappa opioid receptor agonist. © 2022 Published by Elsevier Masson SAS on behalf of Société francophone de néphrologie, dialyse et transplantation.

[Evolution of the incidence and results at 12 months of parathyroidectomy: 40 years of experience in a dialysis center with two successive surgical departments]. / Évolution de l'incidence et des résultats à 12 mois de la parathyroïdectomie : 40 ans d'expérience dans un centre de dialyse avec deux services de chirurgie successifs.

INTRODUCTION: Secondary hyperparathyroidism remains the main complication of mineral and bone metabolism in patients with chronic kidney disease. In case of resistance to medical treatment (native and active vitamin D, calcium and calcimimetics), surgical parathyroidectomy is indicated. The aim of this retrospective study is to show the evolution of the incidence and results of surgical parathyroidectomy in our center between 1980 and 2020 as patient characteristics, diagnostic and therapeutic strategies have changed. PATIENTS AND METHODS: We collected data from dialysis patients who had a first surgical parathyroidectomy between 2000 and 2020 (period 2) in the same surgical department and compared them with historical data between 1980 and 1999 (period 1) operated in one other center. RESULTS: In period 1, 53 surgical parathyroidectomy were performed (2.78/year, 0 to 5, 8.5/1000 patients-year) vs.56 surgical parathyroidectomy in period 2 (2.8/year, 0 to 9, 8/1000 patients-year). The patients of the 2 periods were comparable except for the higher dialysis vintage in period 1 (149±170 vs.89±94 months; P=0.02). In comparison with dialysis patients not requiring surgical parathyroidectomy during the same period, patients who had surgical parathyroidectomy were younger, had higher dialysis vintage and lower diabetes prevalence, but more frequently carriers of glomerulopathy or polycystosis. Systematically performed in period 2, cervical ultrasound identified at least one visible gland in 78.6% of cases while the scintigraphy, performed only in 66% of cases, found at least one gland in 81% of cases. Twelve months after surgery, PTH > 300 pg/mL (marker of secondary hyperparathyroidism recurrence or surgery failure) was present in 30% of patients in period 1 vs. 5.3% in period 2. Hypoparathyroidism was also more frequently observed in period 2 (35.7 vs. 18.8%). Surgical complications were also higher in period 1. CONCLUSION: Despite therapeutic and strategic advances, severe secondary hyperparathyroidism is still as common as ever. It is favored by excessively high PTH targets, by suboptimal prevention before dialysis and poor tolerance of calcimimetics. The surgical parathyroidectomy is effective and safe in the hands of a specialized team with an ultrasound and scintigraphic preoperative assessment.

Sustainability and environmental impact of on-line hemodiafiltration.

Environment has become a main issue of human activities. Chronic hemodialysis (HD) therapy saves lives but consumes large amounts of water and power and produces a lot of care-related waste. On-line hemodiafiltration (HDF) improves patients' outcomes but increases water consumption from ultra-pure water needs and infusion volume. New-generation water treatment systems have much reduced the proportion of reject water that can also be reused. Reducing the dialysate flow in standard HD decreases significantly the water consumption but impacts negatively dialysis efficiency. When on-line HDF is prescribed, reducing the dialysate flow may be applied to decrease water needs while maintaining dialysis efficiency. Nowadays, dialysis prescription cannot ignore its impact on natural resources and environment.

Impact of First Wave COVID-19 Crisis on Dialysis Parameters of COVID-Free Hemodialysis Patients: A NephoCare France Longitudinal Retrospective Cohort Study.

BACKGROUND: Chronic hemodialysis (HD) patients are at high risk of severe COVID-19 with a high risk of death. The organization of dialysis units to treat chronic HD patients with COVID-19 is demanding to prevent virus transmission both in COVID-free patients and the staff. These constraints may have an impact on the dialysis delivery to COVID-free HD patients. We report our experience in French NephroCare (NC) centers. METHODS: We report retrospectively dialysis and nutritional indicators among COVID-free prevalent chronic HD patients' cohort treated in French NC units from February 2020 to April 2020. The COVID-free HD patients were split into 2 subgroups for the analysis, Paris region and other regions because the incidence of COVID-19 was different according to the French regions. RESULTS: The Paris region was the most impacted by COVID-19 with 73% of all the contaminations that occurred in French NC units (n = 118). The dialysis frequency was not reduced all over the NC regions. 2,110 COVID-free HD patients were split into 2 subgroups including Paris region (748 patients) and other regions (1,362 patients). The weekly treatment time decreased significantly in Paris region from February to April (723-696 min [p < 0.00001]) but remained stable in the other regions. The processed blood volume, KT/V, and convective volume declined significantly in the Paris region subgroup but not in other regions. The 3-month weight loss significantly increased in the whole group of patients whatever the region from 0.0 to 0.2% between February 2020 and April 2020 (p < 0.00001). Ultrafiltration rate (UFR) and the normalized proteic catabolic rate remained stable all along the period. The stepwise regression analysis identified February serum albumin level and April UFR as negatively associated with 3-month weight loss. CONCLUSION: HD delivery to COVID-free HD patients was negatively impacted in the Paris region because of the strong constraints on units' organization related to the treatment of COVID-19+ HD patients and with a higher proportion of limited care/self-care units with less staff resources. The 3-month weight loss increase may be related to the suppression of intradialytic snack that impacted mostly the more malnourished patients or patients with lower interdialytic weight gain. These consequences of the COVID-19 crisis on COVID-free HD patients must be recognized and corrected to prevent further deleterious effects on patients' outcomes.

[COVID-19 crisis management during the first three waves in a large dialysis organisation: Feedback from NephroCare France]. / Gestion de la crise COVID-19 dans une organisation multicentrique de dialyse au cours des trois premières vagues : retour d'expérience de NephroCare France.

At the start of the COVID crisis, NephroCare operated 40 dialysis units in 7 regions, with 2,740 hemodialysis patients. The national COVID-19 crisis team implemented early the necessary measures to ensure the safety of dialysis patients and caregivers in the context of the pandemic. These measures were mostly traditional, but some were specific to our organization. They were modified during the 3 successive waves. The first wave mainly impacted NephroCare Ile-de-France which recorded 75% of the contaminations with an impact on the dialysis parameters of non-COVID patients which was not found during the second wave due to reduced stress (34% of contaminations) and a better management of COVID+ patients. The effectiveness of the measures put in place is suggested by the absence of PCR+ in asymptomatic patients and the perfect adequacy of the anti-SARS-CoV2 antibodies with the diagnosis of COVID in one severely impacted Ile-de-France unit, opposite to literature reporting significant rates of positive PCR or serology in asymptomatic patients. In addition, the contamination rate was calculated below the national rate reported by the Biomedicine Agency. The third wave was marked by the implementation of the anti-SARS-CoV2 vaccination with a proportion of vaccinated patients not different from national data and a decrease in COVID cases at the end of the third wave while the national incidence remained stable on the period. In conclusion, this experience of facing an unprecedented serious situation showed the responsiveness of the organization, significant innovations and the efficacy of the implemented measures.

Arterial Versus Venous Port Site Administration of Nadroparin for Preventing Thrombosis of Extracorporeal Blood Circuits in Patients Receiving Hemodiafiltration Treatment.

INTRODUCTION: Administration of low-molecular-weight heparins (LMWHs) is necessary for preventing extracorporeal circuit thrombosis during hemodialysis. A substantial amount of LMWH is removed with online hemodiafiltration (OL-HDF) when administered through the inlet site of the extracorporeal circuit. Consequently, administration of LMWH at the outlet site appears to be more efficient. In this study we aimed to compare the effects of nadroparin calcium (NAD) administered through the outlet versus the inlet port site in postdilution OL-HDF and assess the NAD dose reduction. METHODS: Forty-nine hemodialysis patients were included in 3 consecutive 6-week studies as follows: phase I, inlet port line; phase II, outlet port line; and phase III, outlet port line with reduced dose. We evaluated clotting in the hemodialyzer and venous bubble trap, the dialysis dose (K t/V), and substitution volume. RESULTS: Thirty four percent, 63%, and 66% were categorized as "white" during phases I, II, and III, respectively. During phases I, II, and III, 75%, 93%, and 95% of the venous bubble traps were "clean," and 9%, 0.6%, and 0.4% of the dialyzers clotted, respectively. Average NAD dose was 0.43 ml during phase I and 0.3 ml during phase II. During phase III, the LMWH dose was reduced by 33% to 50% in 15 patients. In phase III, Kt/V improved from 1.64 to 1.75 and substitution volume increased from 20.18 to 21.96 L. CONCLUSIONS: When using OL-HDF, a single administration of NAD at the outlet port line allows for a significant dose reduction and was associated with improved dialysis performance.

[Natriuretic peptides in dialysis: From theory to clinical practice]. / Les peptides natriurétiques en dialyse : de la théorie à la pratique.

Cardiologists and emergency-wards physicians are used to check natriuretic peptides serum level, mainly B-type natriuretic peptide and N-terminal pro-Brain natriuretic peptide for acute cardiac failure diagnosis. Due to their accumulation in chronic kidney disease and their elimination by dialysis, natriuretic peptides sampling remains debatable in chronic kidney disease patients. In dialysis patients, high natriuretic peptides values are associated with mortality, left ventricular hypertrophy and cardiac failure. However, a single value cannot provide a reliable diagnosis. Our clinical practice is as follows: First, we prefer B-type natriuretic peptide to N-terminal pro-Brain natriuretic peptide because of its shorter half-life, with less impact of renal function and dialysis, making its interpretation easier in case of advanced chronic kidney disease or in dialysis patients; second, we define a reference value of B-type natriuretic peptide at dry weight from serial measurements; third, the B-type natriuretic peptide changes are interpreted according to extracellular fluid and cardiac status, but also from the arteriovenous fistula blood flow. In stable dialysis patients, B-type natriuretic peptide is sampled monthly and weekly in unstable patients. We illustrate our experience using clinical cases of overhydration, new cardiac disease onset, hypovolemia and arteriovenous fistula with high blood flow. Longitudinal follow-up of B-type natriuretic peptide is an important advance in dialysis patients in order to detect and treat extracellular fluid variations and cardiac disease status early, both important factors associated with hard outcomes.

The scientific principles and technological determinants of haemodialysis membranes.

In most biological or industrial (including medical) separation processes, a membrane is a semipermeable barrier that allows or achieves selective transport between given compartments. In haemodialysis (HD), the semipermeable membrane is in a tubular geometry in the form of miniscule pipes (hollow fibres) and separation processes between compartments involve a complex array of scientific principles and factors that influence the quality of therapy a patient receives. Several conditions need to be met to accomplish the selective and desired removal of substances from blood in the inner cavity (lumen) of the hollow fibres and across the membrane wall into the larger open space surrounding each fibre. Current HD membranes have evolved and improved beyond measure from the experimental membranes available in the early developmental periods of dialysis. Today, the key functional determinants of dialysis membranes have been identified both in terms of their potential to remove uraemic retention solutes (termed 'uraemic toxins') as well subsidiary criteria they must additionally fulfill to avoid undesirable patient reactions or to ensure safety. The production of hundreds of millions of kilometres of hollow fibre membranes is truly a technological achievement to marvel, particularly in ensuring that the fibre dimensions of wall thickness and inner lumen diameter and controlled porosity-all so vital to core solute removal and detoxification functions of dialysis-are maintained for every centimetre length of the fragile fibres. Production of membranes will increase in parallel with the increase in the number of chronic kidney disease (CKD) patients expected to require HD therapies in the future. The provision of high-quality care entails detailed consideration of all aspects of dialysis membranes, as quality cannot in any way be compromised for the life-sustaining-like the natural membranes within all living organisms-function artificial dialysis membranes serve.

The effect of protein-enriched snacks on serum albumin concentration in non-selected haemodialysis patients.

OBJECTIVE: Serum albumin level is not only one of the protein-energy wasting criteria but also a powerful marker of mortality in patients on haemodialysis (HD) treatment. The study aimed to assess the effect of a protein-enriched snack given during HD treatment on serum albumin level. DESIGN AND METHODS: This prospective, single-centre, observational, non-randomized 16-month study was sub-divided into four 4-month periods. Patients on hemodialysis for more than three months and receiving a regular standard snack (8.8 g of protein) during the HD session were included and assigned during four four-month periods to receive either the standard snack or a protein-enriched snack (28.7 g). Patients were not selected based on nutritional criteria. RESULTS: Sixty-six patients completed the study. Serum albumin levels significantly increased, from 3.43 ± 0.28 g/dl in the first period (standard snack) to 3.62 ± 0.32 g/dl (p < 0.0001) in the second period (enriched snack). In the third period (standard snack), albumin levels remained stable (3.61 ± 0.35 g/dl). After the fourth period (enriched snack), serum albumin levels further increased significantly (3.69 ± 0.30 g/dl; p = 0.05 and p = 0.007, respectively). Weight and normalized protein nitrogen appearance remained stable during the 16-month study period. CONCLUSIONS: This study suggests that the intake of a protein-enriched snack during HD treatment, independently from baseline serum albumin level, could significantly increase their serum albumin levels. Serum albumin level is a powerful predictor of mortality; therefore, this simple and effective action could be of real interest to improve patients' outcomes.

The real-world effectiveness of sucroferric oxyhydroxide in European hemodialysis patients: a 1-year retrospective database analysis.

BACKGROUND: The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), demonstrated its effectiveness for lowering serum phosphate levels, with low daily pill burden, in clinical trials of dialysis patients with hyperphosphatemia. This retrospective database analysis evaluated the real-world effectiveness of SFOH for controlling serum phosphate in European hemodialysis patients. METHODS: De-identified patient data were extracted from a clinical database (EuCliD®) for adult hemodialysis patients from France, Italy, Portugal, Russia and Spain who were newly prescribed SFOH for up to 1 year as part of routine clinical care. Serum phosphate and pill burden were compared between baseline (3-month period before starting SFOH) and four consecutive quarterly periods of SFOH therapy (Q1-Q4; 12 months) in the overall cohort and three subgroups: PB-naïve patients treated with SFOH monotherapy (mSFOH), and PB-pretreated patients who were either switched to SFOH monotherapy (PB → mSFOH), or received SFOH in addition to another PB (PB + SFOH). RESULTS: 1096 hemodialysis patients (mean age: 60.6 years; 65.8% male) were analyzed, including 796, 188 and 53 patients in, respectively, the PB + SFOH, mSFOH, and PB → mSFOH groups. In the overall cohort, serum phosphate decreased significantly from 1.88 mmol/L at baseline to 1.77-1.69 mmol/L during Q1-Q4, and the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased from 41.3% at baseline to 56.2-62.7% during SFOH treatment. Mean PB pill burden decreased from 6.3 pills/day at baseline to 5.0-5.3 pills/day during Q1-Q4. The subgroup analysis found the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased significantly from baseline during SFOH treatment in the PB + SFOH group (from 38.1% up to 60.9% [Q2]) and the mSFOH group (from 49.5% up to 75.2% [Q2]), but there were no significant changes in the PB → mSFOH group. For the PB + SFOH group, serum phosphate reductions were achieved with a similar number of PB pills prescribed at baseline prior to SFOH treatment (6.5 vs 6.2 pills/day at Q4). SFOH daily pill burden was low across all 3 subgroups (2.1-2.8 pills/day). CONCLUSION: In this real-world study of European hemodialysis patients, prescription of SFOH as monotherapy to PB-naïve patients, or in addition to existing PB therapy, was associated with significant improvements in serum phosphate control and a low daily pill burden.