Estudio metabólico de los efectos de la hiperacetatemia secundaria a la concentración de ácido acético presente en el líquido de diálisis convencional en pacientes con enfermedad renal crónica estadio 5D en hemodiálisis en comparación con un líquido de diálisis libre de este

En la actualidad, el líquido de diálisis convencional incluye acetato para conseguir su estabilidad química, es decir, para evitar la precipitación de sales de bicarbonato cálcico o magnésico. Esa concentración de acetato, 3-4 mmol/L, que no superaría la capacidad metabólica del ciclo de los ácidos tricarboxílicos (TCA), desencadena, sin embargo, consecuencias clínicas indeseables por mecanismos no bien dilucidados. Su sustitución por citrato se postula como una mejor alternativa, tanto por evitar la hiperacetatemia, como por sus efectos pleiotrópicos. En este estudio prospectivo y cruzado se evaluaron los efectos de la hiperacetatemia, al comparar un líquido de diálisis con acetato con uno con citrato, con tres enfoques. Se evaluaron los efectos sobre inflamación, daño miocárdico, balance de calcio y metabolismo mineral óseo. Se realizó metabolómica dirigida para investigar cambios en el metabolismo intermedio. Y metabolómica no dirigida para identificar metabolitos que pudieran explicar de una manera bioquímica los resultados clínicos descritos. Los resultados muestran que el citrato representa una opción más biocompatible, en términos de mejor perfil inflamatorio y balance aparentemente neutro de calcio; que en la diálisis se produce cetogénesis y se inhibe la degradación de lípidos y aminoácidos; y que se identifican algunos metabolitos cuyas concentraciones difieren con el uso de un líquido u otro, lo que genera hipótesis que podrían, en futuras investigaciones, desvelar los mecanismos implicados en los beneficios del citrato.Currently, conventional dialysis fluid includes acetate to achieve chemical stability, i.e. to avoid the precipitation of calcium or magnesium bicarbonate salts. This concentration of 3-4 mmol/L of acetate, which would not exceed the metabolic capacity of the tricarboxylic acid (TCA) cycle, nevertheless triggers undesirable clinical consequences by mechanisms that are not well elucidated. Its substitution by citrate is postulated as a better alternative for avoiding hyperacetatemia and its pleiotropic effects. In this prospective crossover study, the effects of hyperacetatemia were evaluated by comparing acetate and citrate dialysates from three approaches: the effects on inflammation, myocardial damage, calcium balance and bone mineral metabolism; targeted metabolomics to investigate changes in intermediary metabolism; and untargeted metabolomics to identify metabolites that could explain in a biochemical way the clinical results described. The results show that citrate represents a more biocompatible option in terms of a better inflammatory profile and apparently neutral calcium balance; that dialysis produces ketogenesis and inhibits the degradation of lipids and amino acids; and that the concentrations of some identified metabolites differ with the use of one liquid or another, which generates hypotheses that could, in future research, reveal the mechanisms involved in the benefits of citrate

Creatine Kinase Elevation in Autosomal Dominant Polycystic Kidney Disease Patients on Tolvaptan Treatment

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage kidney disease. Currently, tolvaptan is the only treatment that has proven to delay disease progression. The most notable side effect of this therapy is drug-induced liver injury; however, recently, there have been two reports of creatine kinase (CK) elevation in ADPKD patients on tolvaptan treatment. We set out to monitor and determine the actual incidence of CK elevation and evaluate its potential association with other clinical factors. Methods: This is an observational retrospective multicenter study performed in rapidly progressive ADPKD patients on tolvaptan treatment from Barcelona, Spain. Laboratory tests, demographics, treatment dose, and reported symptoms were collected from October 2018 to March 2021. Results: Ninety-five patients initiated tolvaptan treatment during follow-up. The medication had to be discontinued in 31 (32.6%) patients, primarily due to aquaretic effects (12.6%), elevated liver enzymes (8.4%), and symptomatic or persistently elevated CK levels (3.2%). Moreover, a total of 27 (28.4%) patients had elevated CK levels, with most of them being either transient (12.6%), mild and asymptomatic (4.2%), or resolved after dose reduction (3.2%) or temporary discontinuation (2.1%). Conclusion: We pre-sent the largest cohort that has monitored CK levels in a real-life setting, finding them elevated in 28.4% of patients. More research and monitoring will help us understand the clinical implications and the pathophysiological mechanism of CK elevation in this population

Creatine Kinase Elevation in Autosomal Dominant Polycystic Kidney Disease Patients on Tolvaptan Treatment

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage kidney disease. Currently, tolvaptan is the only treatment that has proven to delay disease progression. The most notable side effect of this therapy is drug-induced liver injury; however, recently, there have been two reports of creatine kinase (CK) elevation in ADPKD patients on tolvaptan treatment. We set out to monitor and determine the actual incidence of CK elevation and evaluate its potential association with other clinical factors. This is an observational retrospective multicenter study performed in rapidly progressive ADPKD patients on tolvaptan treatment from Barcelona, Spain. Laboratory tests, demographics, treatment dose, and reported symptoms were collected from October 2018 to March 2021. Ninety-five patients initiated tolvaptan treatment during follow-up. The medication had to be discontinued in 31 (32.6%) patients, primarily due to aquaretic effects (12.6%), elevated liver enzymes (8.4%), and symptomatic or persistently elevated CK levels (3.2%). Moreover, a total of 27 (28.4%) patients had elevated CK levels, with most of them being either transient (12.6%), mild and asymptomatic (4.2%), or resolved after dose reduction (3.2%) or temporary discontinuation (2.1%). We pre­sent the largest cohort that has monitored CK levels in a real-life setting, finding them elevated in 28.4% of patients. More research and monitoring will help us understand the clinical implications and the pathophysiological mechanism of CK elevation in this population

Latest Trends in Hemodiafiltration

This review provides a detailed analysis of hemodiafiltration (HDF), its progress from an emerging technique to a potential conventional treatment for chronic hemodialysis patients, and its current status. The article covers the advances, methods, and clinical benefits of HDF, specifically focusing on its impact on cardiovascular health, survival rates, and overall well-being. The review also addresses questions about the safety of HDF and provides evidence to dispel concerns related to the elimination of beneficial substances and infection risks. Additionally, the article explores the potential implications of expanded hemodialysis (HDx) as an alternative to HDF, its classification, safety profile, and an ongoing trial assessing its non-inferiority to HDF. Supported by evidence from randomized controlled trials and observational studies, the review emphasizes the superiority of HDF as a hemodialysis modality and advocates for its positioning as the gold standard in treatment. However, it acknowledges the need for extensive research to define the role of HDx in comprehensive treatment approaches in individuals undergoing dialysis. The synthesis of current knowledge underscores the importance of ongoing exploration and research to refine hemodialysis practices for optimal patient outcomes

Anemia in Chronic Kidney Disease: From Pathophysiology and Current Treatments, to Future Agents

Anemia is a common complication in chronic kidney disease (CKD), and is associated with a reduced quality of life, and an increased morbidity and mortality. The mechanisms involved in anemia associated to CKD are diverse and complex. They include a decrease in endogenous erythropoietin (EPO) production, absolute and/or functional iron deficiency, and inflammation with increased hepcidin levels, among others. Patients are most commonly managed with oral or intravenous iron supplements and with erythropoiesis stimulating agents (ESA). However, these treatments have associated risks, and sometimes are insufficiently effective. Nonetheless, in the last years, there have been some remarkable advances in the treatment of CKD-related anemia, which have raised great expectations. On the one hand, a novel family of drugs has been developed: the hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). These agents induce, among other effects, an increase in the production of endogenous EPO, improve iron availability and reduce hepcidin levels. Some of them have already received marketing authorization. On the other hand, recent clinical trials have elucidated important aspects of iron supplementation, which may change the treatment targets in the future. This article reviews the current knowledge of the pathophysiology CKD-related anemia, current and future therapies, the trends in patient management and the unmet goals

Humoral Response after Three Doses of mRNA-1273 or BNT162b2 SARS-CoV-2 Vaccines in Hemodialysis Patients

The COVID-19 pandemic continues to be a worldwide health issue. Among hemodialysis (HD) patients, two-dose immunization schemes with mRNA vaccines have contributed to preventing severe COVID-19 cases; however, some have not produced a sufficient humoral response, and most have developed a rapid decline in antibody levels over the months following vaccination. This observational, prospective, multi-center study evaluated the humoral response in terms of presence and levels of IgG antibodies to the receptor-binding domain of the S1 spike antigen of SARS-CoV-2 (anti-S1-RBD IgG) to the third dose of SARS-CoV-2 mRNA vaccines, either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer), in 153 patients from three dialysis units affiliated to Hospital Clínic of Barcelona (Spain). Most hemodialysis patients responded intensely to this third vaccine dose, achieving the seroconversion in three out of four non- or weak responders to two doses. Moreover, 96.1% maintained the upper limit or generated higher titers than after the second. BNT162b2 vaccine, active cancer, and immunosuppressive treatment were related to a worse humoral response. Every hemodialysis patient should be administered a third vaccine dose six months after receiving the second one. Despite the lack of data, immunosuppressed patients and those with active cancer may benefit from more frequent vaccine boosters

Humoral Response after Three Doses of mRNA-1273 or BNT162b2 SARS-CoV-2 Vaccines in Hemodialysis Patients

The COVID-19 pandemic continues to be a worldwide health issue. Among hemodialysis (HD) patients, two-dose immunization schemes with mRNA vaccines have contributed to preventing severe COVID-19 cases; however, some have not produced a sufficient humoral response, and most have developed a rapid decline in antibody levels over the months following vaccination. This observational, prospective, multi-center study evaluated the humoral response in terms of presence and levels of IgG antibodies to the receptor-binding domain of the S1 spike antigen of SARS-CoV-2 (anti-S1-RBD IgG) to the third dose of SARS-CoV-2 mRNA vaccines, either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer), in 153 patients from three dialysis units affiliated to Hospital Clínic of Barcelona (Spain). Most hemodialysis patients responded intensely to this third vaccine dose, achieving the seroconversion in three out of four non- or weak responders to two doses. Moreover, 96.1% maintained the upper limit or generated higher titers than after the second. BNT162b2 vaccine, active cancer, and immunosuppressive treatment were related to a worse humoral response. Every hemodialysis patient should be administered a third vaccine dose six months after receiving the second one. Despite the lack of data, immunosuppressed patients and those with active cancer may benefit from more frequent vaccine boosters

Non-valvular Atrial Fibrillation in CKD: Role of Vitamin K Antagonists and Direct Oral Anticoagulants. A Narrative Review

Atrial fibrillation (AF) is the most common arrhythmia in chronic kidney disease (CKD), with a close bidirectional relationship between the two entities. The presence of CKD in AF increases the risk of thromboembolic events, mortality and bleeding. Vitamin K antagonists (VKA) have been the mainstay of treatment for the prevention of thromboembolic events in AF until recently, with confirmed benefits in AF patients with stage 3 CKD. However, the risk-benefit profile of VKA in patients with AF and stages 4-5 CKD is controversial due to the lack of evidence from randomized controlled trials. Treatment with VKA in CKD patients has been associated with conditions such as poorer anticoagulation quality, increased risk of bleeding, faster progression of vascular/valvular calcification and higher risk of calciphylaxis. Direct oral anticoagulants (DOACs) have shown equal or greater efficacy in stroke/systemic embolism prevention, and a better safety profile than VKA in post-hoc analysis of the pivotal randomized controlled trials in patients with non-valvular AF and stage 3 CKD, yet evidence of its risk-benefit profile in more advanced stages of CKD is scarce. Observational studies associate DOACs with a good safety/effectiveness profile compared to VKA in non-dialysis CKD patients. Further, DOACs have been associated with a lower risk of acute kidney injury and CKD development/progression than VKA. This narrative review summarizes the evidence of the efficacy and safety of warfarin and DOACs in patients with AF at different CKD stages, as well as their effects on renal function, vascular/valvular calcification and bone health