Displacing the Burden: A Review of Protein-Bound Uremic Toxin Clearance Strategies in Chronic Kidney Disease.

Uremic toxins (UTs), particularly protein-bound uremic toxins (PBUTs), accumulate in chronic kidney disease (CKD) patients, causing significant health complications like uremic syndrome, cardiovascular disease, and immune dysfunction. The binding of PBUTs to plasma proteins such as albumin presents a formidable challenge for clearance, as conventional dialysis is often insufficient. With advancements in the classification and understanding of UTs, spearheaded by the European Uremic Toxins (EUTox) working group, over 120 molecules have been identified, prompting the development of alternative therapeutic strategies. Innovations such as online hemodiafiltration aim to enhance the removal process, while novel adsorptive therapies offer a means to address the high affinity of PBUTs to plasma proteins. Furthermore, the exploration of molecular displacers, designed to increase the free fraction of PBUTs, represents a cutting-edge approach to facilitate their dialytic clearance. Despite these advancements, the clinical application of displacers requires more research to confirm their efficacy and safety. The pursuit of such innovative treatments is crucial for improving the management of uremic toxicity and the overall prognosis of CKD patients, emphasizing the need for ongoing research and clinical trials.

Different Perspectives of Spanish Patients and Professionals on How a Dialysis Unit Should Be Designed.

Aim: The opinion of hemodialysis patients, professionals and family members is rarely considered in the design of a hemodialysis unit. Purpose: To know and compare the opinion and preferences of patients, family members and professionals regarding the design of a dialysis unit and the potential activities they believe should be carried out during the session in order to provide architects with real information for the construction of a dialysis center. Patients and Methods: Anonymous and voluntary survey in electronic format addressed to patients, relatives and professionals belonging to the 18 hemodialysis centers of the renal foundation and to ALCER and its different delegations, in relation to leisure activities to be carried out in the dialysis center and preferred design of the treatment room. The results obtained between the patient-family group and the professionals were compared. Results: We received 331 responses, of which 215 were from patients and family members (65%) and 116 (35%) from professionals. The most represented category among professionals was nursing (53%), followed by assistants (24%) and physicians (12.9%). A higher proportion of patients (66%) preferred rooms in groups of 10-12 patients as opposed to professionals who preferred open-plan rooms (p<0.001). The options that showed the most differences between patients and professionals were chatting with colleagues and intimacy (options most voted by patients/families), versus performing group activities and visibility (professionals). Conclusion: The professionals' view of patients' needs does not always coincide with the patients' perception. The inclusion of the perspective of people with kidney disease continues to be a pending issue in which we must improve both patient organizations and professionals, and the opinion of professionals and patients must be included in the design of a dialysis unit and the activities to be developed in it.

Epidemiology of Fabry disease in patients in hemodialysis in the Madrid community / Epidemiología de la enfermedad de Fabry en pacientes en hemodiálisis de la Comunidad de Madrid

This study screened for Fabry disease (FD) in patients in hemodialysis (HD) in the region of Madrid (CAM) with a cross-sectional design to evaluate HD-prevalent patients, followed by a three-year period prospective design to analyze HD-incident patients. Inclusion criteria: patients older than 18 years on HD in the CAM, excluding patients diagnosed with any other hereditary disease with renal involvement different from FD, that sign the Informed Consent (IC). Exclusion criteria: underaged patients or not agreeing or not being capable of signing the IC. Results: 3470 patients were included, 63% males and with an average age of 67.9±9.7 years. 2357 were HD-prevalent patients and 1113 HD-incident patients. For HD-prevalent patients, average time in HD was 45.2 months (SD 51.3), in HD-incident patients proteinuria was present in 28.4%. There were no statistical differences in plasmatic alpha-galactosidase A (α-GAL-A) activity or Lyso-GL-3 values when comparing HD-prevalent and HD-incident populations and neither between males and females. A genetic study was performed in 87 patients (2.5% of patients): 60 male patients with decreased enzymatic activity and 27 female patients either with a decreased GLA activity, increased Lyso-Gl3 levels or both. The genetic variants identified were: p.Asp313Tyr (4 patients), p.Arg220Gln (3 patients) and M290I (1 patient). None of the identified variants is pathogenic. Conclusions: 76% of HD Centers of the CAM participated in the study. This is the first publication to describe the prevalence of FD in the HD-population of a region of Spain as well as its average α-GAL-A-activity and plasmatic Lyso-Gl3 levels. It is also the first study that combines a cross-sectional design with a prospective follow-up design. This study has not identified any FD patient. (AU)

El objetivo del estudio ha sido realizar un mapa descriptivo de la enfermedad de Fabry (EF) en la Comunidad de Madrid, así como realizar un despistaje de la EF a todo paciente incidente durante un período de 3 años. Criterios de inclusión: Pacientes mayores de 18 años, excluyendo aquellos diagnosticados de cualquier otra enfermedad hereditaria con afectación renal diferente de la EF, que firmaran el consentimiento informado. Criterios de exclusión: pacientes menores de edad, no estar de acuerdo o no ser capaces de firmar el consentimiento informado. Resultados: Se incluyeron 3.470 pacientes (63% hombres), con una edad media de 67,9±9,7 años, de los cuales 2.357 eran pacientes prevalentes y 1.113 incidentes. En el caso de los pacientes prevalentes, el tiempo medio en hemodiálisis (HD) fue de 45,2 (DE 51,3) meses. En pacientes incidentes, la proteinuria estuvo presente en el 28,4%. No hubo diferencias estadísticamente significativas en la actividad plasmática de alfa-galactosidasa A o valores de Lyso-Gl3 al comparar las poblaciones de incidentes y de prevalentes, y tampoco entre hombres y mujeres. Se realizó estudio genético en 87 pacientes (2,5% de los pacientes): 60 varones con disminución de la actividad enzimática y 27 mujeres con una disminución de la actividad enzimática, aumento de los niveles de Lyso-Gl3 o ambos. Las variantes genéticas identificadas fueron: p.Asp313Tyr (4 pacientes), p.Arg220Gln (3 pacientes) y M290I (un paciente). Ninguna de las variantes identificadas fue patógena. Conclusiones: El 76% de los centros de HD de la Comunidad de Madrid participaron en el estudio. Este es el primer estudio epidemiológico prospectivo de EF en la población de HD de una región de España. También es la primera vez que se describen niveles de alfa-galactosidasa A y Lyso-Gl3 en HD, sin embargo, en este estudio no se han identificado pacientes con EF. (AU)

Impact of the COVID-19 Pandemic in Spain in the Successive Pandemic Waves on Hemodialysis Patients and Healthcare Personnel.

(1) Background: The impact of SARS-CoV-2 has been variable over the time course of the pandemic and in different populations. The aim was to analyze the impact of COVID-19 infection in a known population of hemodialysis (HD) patients and professionals in Spain at different times of the pandemic. (2) Methods: We conducted an observational, descriptive study with a follow-up from 3 March 2020 to 23 April 2022 (776 days), using in average of 414 professionals and 1381 patients from 18 HD units in Spain. The data from the positive PCR or the rapid antigen detection test (RADT) subject were analyzed and segmented into six periods (waves). (3) Results: Of 703 positive COVID-19 tests, 524 were HD patients (74.5%), and 179 were HD professionals (25.5%). Overall, 38% of staff and 43% of patients were affected. Differences were observed in regard to incidence (21% vs. 13%), mortality (3.5% vs. 0%), and symptomatology between the patients and professionals and throughout the pandemic. (4) Conclusions: COVID-19 severity varied during different pandemic waves, with a greater impact seen in the first wave. HD professionals and patients had similar infection rates, but patients had higher mortality rates. Community transmission was the primary route of infection.

Recommendations of the Spanish Society of Nephrology for the management of mineral and bone metabolism disorders in patients with chronic kidney disease: 2021 (SEN-MM).

As in 2011, when the Spanish Society of Nephrology (SEN) published the Spanish adaptation to the Kidney Disease: Improving Global Outcomes (KDIGO) universal Guideline on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), this document contains an update and an adaptation of the 2017 KDIGO guidelines to our setting. In this field, as in many other areas of nephrology, it has been impossible to irrefutably answer many questions, which remain pending. However, there is no doubt that the close relationship between the CKD-MBD/cardiovascular disease/morbidity and mortality complex and new randomised clinical trials in some areas and the development of new drugs have yielded significant advances in this field and created the need for this update. We would therefore highlight the slight divergences that we propose in the ideal objectives for biochemical abnormalities in the CKD-MBD complex compared to the KDIGO suggestions (for example, in relation to parathyroid hormone or phosphate), the role of native vitamin D and analogues in the control of secondary hyperparathyroidism and the contribution of new phosphate binders and calcimimetics. Attention should also be drawn to the adoption of important new developments in the diagnosis of bone abnormalities in patients with kidney disease and to the need to be more proactive in treating them. In any event, the current speed at which innovations are taking place, while perhaps slower than we might like, globally drives the need for more frequent updates (for example, through Nefrología al día).

The role of bioimpedance analysis in overweight and obese patients with acute heart failure: a pilot study.

AIMS: Residual congestion at the time of hospital discharge is an important readmission risk factor, and its detection with physical examination and usual diagnostic techniques have strong limitations in overweight and obese patients. New tools like bioelectrical impedance analysis (BIA) could help to determine when euvolaemia is reached. The aim of this study was to investigate the usefulness of BIA in management of heart failure (HF) in overweight and obese patients. METHODS AND RESULTS: Our study is a single-centre, single-blind, randomized controlled trial that included 48 overweight and obese patients admitted for acute HF. The study population was randomized into two arms: BIA-guided group and standard care. Serum electrolytes, kidney function, and natriuretic peptides were followed up during their hospital stay and at 90 days after discharge. The primary endpoint was development of severe acute kidney injury (AKI) defined as an increase in serum creatinine by >0.5 mg/dL during hospitalization, and the main secondary endpoint was the reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels during hospitalization and within 90 days after discharge. The BIA-guided group showed a remarkable lower incidence of severe AKI, although no significant differences were found (41.4% vs. 16.7%; P = 0.057). The proportion of patients who achieved levels of NT-proBNP < 1000 pg/mL at 90 days was significantly higher in the BIA-guided group than in the standard group (58.8% vs. 25%; P = 0.049). No differences were observed in the incidence of adverse outcomes at 90 days. CONCLUSIONS: Among overweight and obese patients with HF, BIA reduces NT-proBNP levels at 90 days compared with standard care. In addition, there is a trend towards lower incidence of AKI in the BIA-guided group. Although more studies are required, BIA could be a useful tool in decompensated HF management in overweight and obese patients.

Time-averaged concentration estimation of uraemic toxins with different removal kinetics: a novel approach based on intradialytic spent dialysate measurements.

Background: Kt/Vurea is the most used marker to estimate dialysis adequacy; however, it does not reflect the removal of many other uraemic toxins, and a new approach is needed. We have assessed the feasibility of estimating intradialytic serum time-averaged concentration (TAC) of various uraemic toxins from their spent dialysate concentrations that can be estimated non-invasively online with optical methods. Methods: Serum and spent dialysate levels and total removed solute (TRS) of urea, uric acid (UA), indoxyl sulphate (IS) and ß2-microglobulin (ß2M) were evaluated with laboratory methods during 312 haemodialysis sessions in 78 patients with four different dialysis treatment settings. TAC was calculated from serum concentrations and evaluated from TRS and logarithmic mean concentrations of spent dialysate (MlnD). Results: Mean (± standard deviation) intradialytic serum TAC values of urea, UA, ß2M and IS were 10.4 ± 3.8 mmol/L, 191.6 ± 48.1 µmol/L, 13.3 ± 4.3 mg/L and 82.9 ± 43.3 µmol/L, respectively. These serum TAC values were similar and highly correlated with those estimated from TRS [10.5 ± 3.6 mmol/L (R 2 = 0.92), 191.5 ± 42.8 µmol/L (R 2 = 0.79), 13.0 ± 3.2 mg/L (R 2 = 0.59) and 82.7 ± 40.0 µmol/L (R 2 = 0.85)] and from MlnD [10.7 ± 3.7 mmol/L (R 2 = 0.92), 191.6 ± 43.8 µmol/L (R 2 = 0.80), 12.9 ± 3.2 mg/L (R 2 = 0.63) and 82.2 ± 38.6 µmol/L (R 2 = 0.84)], respectively. Conclusions: Intradialytic serum TAC of different uraemic toxins can be estimated non-invasively from their concentration in spent dialysate. This sets the stage for TAC estimation from online optical monitoring of spent dialysate concentrations of diverse solutes and for further optimization of estimation models for each uraemic toxin.

Maintenance of Potent Cellular and Humoral Immune Responses in Long-Term Hemodialysis Patients after 1273-mRNA SARS-CoV-2 Vaccination.

Continuous evaluation of the coronavirus disease 2019 (COVID-19) vaccine effectiveness in hemodialysis (HD) patients is critical in this immunocompromised patient group with higher mortality rates due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The response towards vaccination in HD patients has been studied weeks after their first and second SARS-CoV-2 vaccination dose administration, but no further studies have been developed in a long-term manner, especially including both the humoral and cellular immune response. Longitudinal studies that monitor the immune response to COVID-19 vaccination in individuals undergoing HD are therefore necessary to prioritize vaccination strategies and minimize the pathogenic effects of SARS-CoV-2 in this high-risk group of patients. We followed up HD patients and healthy volunteers (HV) and monitored their humoral and cellular immune response three months after the second (V2+3M) and after the third vaccination dose (V3+3M), taking into consideration previous COVID-19 infections. Our cellular immunity results show that, while HD patients and HV individuals secrete comparable levels of IFN-γ and IL-2 in ex vivo stimulated whole blood at V2+3M in both naïve and COVID-19-recovered individuals, HD patients secrete higher levels of IFN-γ and IL-2 than HV at V3+3M. This is mainly due to a decay in the cellular immune response in HV individuals after the third dose. In contrast, our humoral immunity results show similar IgG binding antibody units (BAU) between HD patients and HV individuals at V3+3M, independently of their previous infection status. Overall, our results indicate that HD patients maintain strong cellular and humoral immune responses after repeated 1273-mRNA SARS-CoV-2 vaccinations over time. The data also highlights significant differences between cellular and humoral immunity after SARS-CoV-2 vaccination, which emphasizes the importance of monitoring both arms of the immune response in the immunocompromised population.

Vitamin D, Cellular Senescence and Chronic Kidney Diseases: What Is Missing in the Equation?

As life expectancy increases in many countries, the prevalence of age-related diseases also rises. Among these conditions, chronic kidney disease is predicted to become the second cause of death in some countries before the end of the century. An important problem with kidney diseases is the lack of biomarkers to detect early damage or to predict the progression to renal failure. In addition, current treatments only retard kidney disease progression, and better tools are needed. Preclinical research has shown the involvement of the activation of cellular senescence-related mechanisms in natural aging and kidney injury. Intensive research is searching for novel treatments for kidney diseases as well as for anti-aging therapies. In this sense, many experimental shreds of evidence support that treatment with vitamin D or its analogs can exert pleiotropic protective effects in kidney injury. Moreover, vitamin D deficiency has been described in patients with kidney diseases. Here, we review recent evidence about the relationship between vitamin D and kidney diseases, explaining the underlying mechanisms of the effect of vitamin D actions, with particular attention to the modulation of cellular senescence mechanisms.

Epidemiology of Fabry disease in patients in hemodialysis in the Madrid community.

This study screened for Fabry disease (FD) in patients in hemodialysis (HD) in the region of Madrid (CAM) with a cross-sectional design to evaluate HD-prevalent patients, followed by a three-year period prospective design to analyze HD-incident patients. INCLUSION CRITERIA: patients older than 18 years on HD in the CAM, excluding patients diagnosed with any other hereditary disease with renal involvement different from FD, that sign the Informed Consent (IC). EXCLUSION CRITERIA: underaged patients or not agreeing or not being capable of signing the IC. RESULTS: 3470 patients were included, 63% males and with an average age of 67.9±9.7 years. 2357 were HD-prevalent patients and 1113 HD-incident patients. For HD-prevalent patients, average time in HD was 45.2 months (SD 51.3), in HD-incident patients proteinuria was present in 28.4%. There were no statistical differences in plasmatic alpha-galactosidase A (α-GAL-A) activity or Lyso-GL-3 values when comparing HD-prevalent and HD-incident populations and neither between males and females. A genetic study was performed in 87 patients (2.5% of patients): 60 male patients with decreased enzymatic activity and 27 female patients either with a decreased GLA activity, increased Lyso-Gl3 levels or both. The genetic variants identified were: p.Asp313Tyr (4 patients), p.Arg220Gln (3 patients) and M290I (1 patient). None of the identified variants is pathogenic. CONCLUSIONS: 76% of HD Centers of the CAM participated in the study. This is the first publication to describe the prevalence of FD in the HD-population of a region of Spain as well as its average α-GAL-A-activity and plasmatic Lyso-Gl3 levels. It is also the first study that combines a cross-sectional design with a prospective follow-up design. This study has not identified any FD patient.

Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study.

Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods: This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results: A total of 711 patients [67% male, median age (range) 67 (20-89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P = .001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P = .693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P = .001), lower time from booster (P = .043) and past breakthrough SARS-CoV-2 infection (P < .001). Conclusions: In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infection.

Impact of different COVID-19 waves on kidney replacement therapy epidemiology and mortality: REMER 2020.

BACKGROUND: Kidney replacement therapy (KRT) confers the highest risk of death from coronavirus disease 2019 (COVID-19). However, most data refer to the early pandemic waves. Whole-year analysis compared with prior secular trends are scarce. METHODS: We present the 2020 REMER Madrid KRT registry, corresponding to the Spanish Region hardest hit by COVID-19. RESULTS: In 2020, KRT incidence decreased 12% versus 2019, while KRT prevalence decreased by 1.75% for the first time since records began and the number of kidney transplants (KTs) decreased by 16%. Mortality on KRT was 10.2% (34% higher than the mean for 2008-2019). The 2019-2020 increase in mortality was larger for KTs (+68%) than for haemodialysis (+24%) or peritoneal dialysis (+38%). The most common cause of death was infection [n = 419 (48% of deaths)], followed by cardiovascular [n = 200 (23%)]. Deaths from infection increased by 167% year over year and accounted for 95% of excess deaths in 2020 over 2019. COVID-19 was the most common cause of death (68% of infection deaths, 33% of total deaths). The bulk of COVID-19 deaths [209/285 (73%)] occurred during the first COVID-19 wave, which roughly accounted for the increased mortality in 2020. Being a KT recipient was an independent risk factor for COVID-19 death. CONCLUSIONS: COVID-19 negatively impacted the incidence and prevalence of KRT, but the increase in KRT deaths was localized to the first wave of the pandemic. The increased annual mortality argues against COVID-19 accelerating the death of patients with short life expectancy and the temporal pattern of COVID-19 mortality suggests that appropriate healthcare may improve outcomes.

Evaluation of the impact of an intradialytic exercise programme on sarcopaenia in very elderly haemodialysis patients.

Sarcopaenia is a highly prevalent condition in persons on haemodialysis (HD). In stable very elderly (75-95 years old) persons on chronic HD, we prospectively studied the European Working Group on Sarcopaenia in Older People (EWGSOP2) steps stability over time in 37 controls and their response to a 12-week intradialytic lower limb exercise programme in 23 persons. Overall dropout was 15% and the main cause for dropout was death (8%). Thus 33 controls and 18 exercise participants were evaluated at 12 weeks. In controls, comorbidity, nutrition, dependency and frailty scales, anthropometric assessments, EWGSOP2 step values and the prevalence of suspected, confirmed and severe sarcopaenia as assessed by EWGSOP2 remained stable. In contrast, in persons who completed the exercise programme, a significant improvement in the five times sit-to-stand (STS-5) test was noted at the end of the 12-week exercise programme (19.2 ± 4.9-15.9 ± 5.9 seconds; P = .001), consistent with the lower limb nature of the exercise programme, that persisted 12 weeks after completion of the programme. Exercise also improved the Fried frailty scale (1.7 ± 1.0-1.1 ± 0.6; P = .004). In conclusion, EWGSOP2 steps remain stable in stable very elderly persons on HD and STS-5 is responsive to a short-term intradialytic lower limb exercise programme. These results may help define EWGSOP2-based primary endpoints in future large-scale clinical trials assessing exercise interventions.

Impact of the COVID pandemic on vascular access creation for haemodialysis in 16 Spanish haemodialysis centres.

Background: The coronavirus disease (COVID) pandemic has resulted in a major disruption in healthcare that has affected several medical and surgical specialties. European and American Vascular Societies have proposed deferring the creation of an elective vascular access (VA) [autologous or prosthetic arteriovenous fistula (AVF) or arteriovenous graft (AVG)] in incident patients on haemodialysis (HD) in the era of the COVID pandemic. The aim of this study is to examine the impact of the COVID pandemic on VA creation and the central venous catheter (CVC)-related hospitalizations and complications in HD patients dialyzed in 16 Spanish HD units of three different regions. Methods: We compared retrospectively two periods of time: the pre-COVID (1 January 2019-11 March 2020) and the COVID era (12 March 2020-30 June 2021) in all HD patients (prevalent and incident) dialyzed in our 16 HD centres. The variables analysed were type of VA (CVC, AVF and AVG) created, percentage of CVC in incident and prevalent HD patients, CVC-related hospitalizations and complications (infection, extrusion, disfunction, catheter removal) and percentage of CVC HD sessions that did not reach the goal of Kt (>45) as a marker of HD adequacy. Results: A total of 1791 VAs for HD were created and 905 patients started HD during the study period. Patients who underwent vascular access surgery during the COVID period compared with pre-COVID period were significantly younger, with a significant decrease in surgical activity to create AVFs and AVGs in older HD patients (>75 and >85 years of age). There was a significant increase in CVC placement (from 59.7% to 69.5%; P < 0.001) from the pre-COVID to the COVID period. During the COVID pandemic, a significantly higher number of patients started HD through a CVC (80.3% versus 69.1%; P < 0.001). The percentage of CVC in prevalent HD patients has not decreased in the 19 months since the start of the pandemic [414 CVC/1058 prevalent patients (39.4%)]. No significant changes were detected in CVC-related hospitalizations between the pre-COVID and COVID periods. In the COVID period, a significant increase in catheter replacement and the percentage of HD session that did not reach the HD dose objective (Kt > 45) was observed. Conclusions: COVID has presented a public health system crisis that has influenced VA for HD, with an increase in CVCs relative to AVFs. A decrease in HD sessions that did not reach the HD dose objective was observed in the COVID period compared with a pre-COVID period.

Sarcopenia and Mortality in Older Hemodialysis Patients.

(1) Sarcopenia is a progressive loss of skeletal muscle mass and strength. The aim of this study was to determine the association of sarcopenia, defined according to the Working Group on Sarcopenia in Older People (EWGSOP2) diagnostic criteria, with mortality at 24 months in very elderly hemodialysis patients. (2) A prospective study was conducted in 60 patients on chronic hemodialysis who were older than 75 years. Sarcopenia was diagnosed according to EWGSOP2 criteria. Additionally, clinical, anthropometric and analytical variables and body composition by bioimpedance were assessed. The date and cause of death were recorded during 2 years of follow-up. (3) Among study participants, 41 (68%) were men, the mean age 81.85 ± 5.58 years and the dialysis vintage was 49.88 ± 40.29 months. The prevalence of probable sarcopenia was 75% to 97%, depending on the criteria employed: confirmed sarcopenia ranged from 37 to 40%, and severe sarcopenia ranged from 18 to 37%. A total of 30 (50%) patients died over 24 months. Sarcopenia probability variables were not related to mortality. In contrast, sarcopenia confirmation (appendicular skeletal muscle mass, ASM) and severity (gait speed, GS) variables were associated with mortality. In multivariate analysis, the hazard ratio (95% confidence interval) for all-cause death was 3.03 (1.14-8.08, p = 0.028) for patients fulfilling ASM sarcopenia criteria and 3.29 (1.04-10.39, p = 0.042) for patients fulfilling GS sarcopenia criteria. (4) The diagnosis of sarcopenia by EWGSOP2 criteria is associated with an increased risk of all-cause death in elderly dialysis patients. Specifically, ASM and GS criteria could be used as mortality risk markers in elderly hemodialysis patients. Future studies should address whether the early diagnosis and treatment of sarcopenia improve outcomes.

Development of Potent Cellular and Humoral Immune Responses in Long-Term Hemodialysis Patients After 1273-mRNA SARS-CoV-2 Vaccination.

Long-term hemodialysis (HD) patients are considered vulnerable and at high-risk of developing severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection due to their immunocompromised condition. Since COVID-19 associated mortality rates are higher in HD patients, vaccination is critical to protect them. The response towards vaccination against COVID-19 in HD patients is still uncertain and, in particular the cellular immune response is not fully understood. We monitored the humoral and cellular immune responses by analysis of the serological responses and Spike-specific cellular immunity in COVID-19-recovered and naïve HD patients in a longitudinal study shortly after vaccination to determine the protective effects of 1273-mRNA vaccination against SARS-CoV-2 in these high-risk patients. In naïve HD patients, the cellular immune response measured by IL-2 and IFN-É£ secretion needed a second vaccine dose to significantly increase, with a similar pattern for the humoral response. In contrast, COVID-19 recovered HD patients developed a potent and rapid cellular and humoral immune response after the first vaccine dose. Interestingly, when comparing COVID-19 recovered healthy volunteers (HV), previously vaccinated with BNT162b2 vaccine to HD patients vaccinated with 1273-mRNA, these exhibited a more robust immune response that is maintained longitudinally. Our results indicate that HD patients develop strong cellular and humoral immune responses to 1273-mRNA vaccination and argue in favor of personalized immune monitoring studies in HD patients, especially if COVID-19 pre-exposed, to adapt COVID-19 vaccination protocols for this immunocompromised population.

Increased 1-year mortality in haemodialysis patients with COVID-19: a prospective, observational study.

BACKGROUND: Dialysis confers the highest risk of coronavirus disease 2019 (COVID-19) death among comorbidities predisposing to severe COVID-19. However, reports of COVID-19-associated mortality frequently refer to mortality during the initial hospitalization or first month after diagnosis. METHODS: In a prospective, observational study, we analysed the long-term (1-year follow-up) serological and clinical outcomes of 56 haemodialysis (HD) patients who were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first pandemic wave. COVID-19 was diagnosed by a positive polymerase chain reaction (PCR) test (n = 37) or by the development of anti-SARS-CoV-2 antibodies (n = 19). RESULTS: After >1 year of follow-up, 35.7% of HD patients infected by SARS-CoV-2 during the first pandemic wave had died, 6 (11%) during the initial admission and 14 (25%) in the following months, mainly within the first 3 months after diagnosis. Overall, 30% of patients died from vascular causes and 40% from respiratory causes. In adjusted analysis, a positive SARS-CoV-2 PCR test for diagnosis {hazard ratio [HR] 5.18 [interquartile range (IQR) 1.30-20.65], P = 0.020}, higher baseline C-reactive protein levels [HR 1.10 (IQR 1.03-1.16), P = 0.002] and lower haemoglobin levels [HR 0.62 (IQR 0.45-0.86), P = 0.005] were associated with higher 1-year mortality. Mortality in the 144 patients who did not have COVID-19 was 21 (14.6%) over 12 months [HR of death for COVID-19 patients 3.00 (IQR 1.62-5.53), log-rank P = 0.00023]. Over the first year, the percentage of patients having anti-SARS-CoV-2 immunoglobulin G (IgG) decreased from 36/49 (73.4%) initially to 27/44 (61.3%) at 6 months and 14/36 (38.8%) at 12 months. CONCLUSIONS: The high mortality of HD patients with COVID-19 is not limited to the initial hospitalization. Defining COVID-19 deaths as those occurring within 3 months of a COVID-19 diagnosis may better represent the burden of COVID-19. In HD patients, the anti-SARS-CoV-2 IgG response was suboptimal and short-lived.

Sarcopenia assessed by 4-step EWGSOP2 in elderly hemodialysis patients: Feasibility and limitations.

BACKGROUND: In 2019, EWGSOP2 proposed 4 steps to diagnose and assess sarcopenia. We aimed to quantify the prevalence of sarcopenia according to the EWGSOP2 diagnostic algorithm and to assess its applicability in elderly patients on hemodialysis. METHODS: Prospective study of 60 outpatients on chronic hemodialysis aged 75- to 95-years, sarcopenia was assessed according to the 4-step EWGSOP2: Find: Strength, Assistance walking, Rise from a chair, Climb stairs, and Falls (SARC-F); Assess: grip strength by dynamometry (GSD) and sit to stand to sit 5 (STS5); Confirm: appendicular skeletal muscle mass (ASM) by bioimpedance; Severity: gait speed (GS), Timed-Up and Go (TUG), and Short Physical Performance Battery (SPPB). RESULTS: The sequential four steps resulted in a prevalence of confirmed or severe sarcopenia of 20%. Most (97%) patients fulfilled at least one criterion for probable sarcopenia. The sensitivity of SARC-F for confirmed sarcopenia was low (46%). Skipping the SARC-F step increased the prevalence of confirmed and severe sarcopenia to 40% and 37%, respectively. However, 78% of all patients had evidence of dynapenia consistent with severe sarcopenia. Muscle mass (ASM) was normal in 60% of patients, while only 25% had normal muscle strength values (GSD). CONCLUSIONS: According to the 4-step EWGSOP2, the prevalence of confirmed or severe sarcopenia was low in elderly hemodialysis patients. The diagnosis of confirmed sarcopenia underestimated the prevalence of dynapenia consistent with severe sarcopenia. Future studies should address whether a 2-step EWGSOP2 assessment (Assess-Severity) is simpler to apply and may provide better prognostic information than 4-step EWGSOP2 in elderly persons on hemodialysis.