Bisfenol (A) una toxina a tener en cuenta en el enfermo renal en hemodiálisis

Introduction: Most uremic toxins are by-products of protein metabolism by action of intestinal flora. The metabolism of aromatic amino acids originates phenolic type residues. The most studied is p-cresol that is associated with renal function and vascular damage. Bisphenol A (BPA) is an exogenous molecule with characteristics similar to these aromatic uremic toxins. BPA is an estrogenic endocrine disruptor, found in tin cans, plastic bottles, epoxy resins and in some dialyzers. This molecule accumulates in patients who have impaired renal function. Observational studies have shown that exposure of BPA is linked to renal and cardiovascular injury, among many others in humans, and in animal studies a causal link has been described. Kidneys with normal renal function rapidly excrete BPA, but insufficient excretion in patients with CKD results in accumulation of BPA in the body.Muchas toxinas urémicas son originadas como consecuencia del catabolismo proteico por la flora intestinal. El metabolismo de aminoácidos aromáticos origina residuos de tipo fenólico. De estas toxinas, la más estudiada es el p-cresol, que se asocia a la función renal y daño vascular. El Bisfenol A (BPA) es una molécula exógena de características semejantes a estas toxinas urémicas aromáticas. El BPA es un disruptor endocrino estrogénico que se encuentra en latas de conserva, botellas de plástico, resinas epoxi y en algunos dializadores. Esta molécula se acumula en pacientes que tienen deteriorada la función renal. Estudios observacionales han demostrado que una exposición a BPA está vinculada, entre otras muchas, a lesión renal y cardiovascular en los seres humanos; en estudios en animales se ha descrito un vínculo causal. Los riñones con función renal normal excretan rápidamente BPA, pero una excreción insuficiente en pacientes con ERC da lugar a la acumulación del BPA en el organismo

Reactions to synthetic membranes dialyzers: Is there an increase in incidence?

Background: Reactions to dialyzers used in dialysis have been reported more frequently in recent years. Evidence, however, shows that the reaction rate has remained stable for years. Summary: One explanation for the apparent increase in publication frequency could be the lack of knowledge that dialyzer reactions may well occur with biocompatible membranes. Studies showed that the cause of these reactions is very diverse and varied, involving multiple materials. However, polyvinylpyrrolidone continues to be the main suspect, but without conclusive results. There are no differences between the different fibers, and although polysulfone is the most described, it is also the most used. Key Messages: The change to cellulose triacetate continues to be the most appropriate form of treatment. The classification of these reactions into type A and B complicates the diagnosis, and its true usefulness is in doubtThe research presented in this article is supported by the grants from the Spanish Ministry of Economy and Competitiveness and European Regional Development Funds (ERDF/FEDER) through ISCIII/FIS grants PI16/01298, PI17/01495, CIBERDEM and REDINREN RD016/0019 and through the Madrid Renal Society (SOMANE) grant

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-livedThis research received no external funding. The research groups of E.G.-P., S.M. and A.O. are funded by the Ministerio de Economia, Industria y competitividad: FIS/Fondos FEDER (PI16/01298, PI17/00257, PI18/01386, PI19/00588, PI19/00815, PI20/00487, PI21/01430), ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/-0009) and Sociedad Española de Nefrología, Comunidad de Madrid en Biomedicina (B2017/BMD-3686 CIFRA2-CM

The spectrum of clinical and serological features of COVID-19 in urban hemodialysis patients

The inherent immunosuppression of uremia increases the susceptibility of hemodialysis patients to infection. There is still limited evidence on hemodialysis patients and COVID-19. The clinical and analytical spectrum and treatment responses and mortality are poorly characterized. Material and Methods: Clinical and analytical features, chest X-ray, polymerase chain reaction (PCR) and antibodies for SARS-CoV-2, treatment and outcomes were analyzed in 48 patients diagnosed with COVID-19 during March and April 2020 in two coordinated Spanish hemodialysis units. Results: In 200 haemodialysis patients, COVID-19 was diagnosed in 48, of whom 22 were PCR positive, eight PCR negative but seroconverted and two were diagnosed on typical clinical grounds. Despite a mean age of 72.6 years, the overall mortality rate was 5/48 (10%). Among the PCR positive patients, 21 (55%) required admission and five (13%) died. PCR positive patients were more often symptomatic and hospitalized and had higher troponin I levels than PCR negative patients, but did not differ in lymphocyte counts, D-dimer or interleukin-6 (IL-6) levels. Among PCR negative COVID-19 patients, three out of 10 (30%) required admission, and none died. The most frequent symptom among the 48 patients was fever (31%), followed by asymptomatic patients (23%). A low number of lymphocytes was the only parameter significantly different between hospitalized and ambulatory COVID-19 patients, independently of PCR status. Conclusions: COVID-19 hemodialysis patients are frequently asymptomatic, and mortality may be lower than previously reported. Diagnosis may be retrospective, based on seroconversion, as PCR may be negative. This information should guide preventive and patient isolation strategiesResearch support from FIS ISCIII FEDER funds PI16/01298, PI15/00298, PI16/02057, PI16/01900, PI19/00815, DTS18/00032 ISCIII-RETIC REDinREN RD16/0009, CYTED IBERERC and Sociedad Madrileña de Nefrologia, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071), Comunidad de Madrid CIFRA2 B2017/BMD-3686. to A

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 interventionsThe authors would like to thank FRIAT for its support to the present study. The research groups of E.G.P., S.M.F. and A.O. are funded by the Ministerio de Economia, Industria y competitividad: FIS/Fondos FEDER (PI16/01298, PI18/01386, PI19/00588, PI19/00815, PI20/00487, PI21/01240, DTS18/00032), ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009) and Sociedad Española de Nefrología, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-C

Fibrosis of Peritoneal Membrane, Molecular Indicators of Aging and Frailty Unveil Vulnerable Patients in Long-Term Peritoneal Dialysis

Funding: Sociedade Portuguesa de Nefrologia (SPN) SPN funded a project and Ana Rita Martins, MD, Nephrology fellow, for a residence at Jiménez Díaz Foundation University Hospital, Madrid under the scope of novel serum biomarkers of CKD. iNOVA4Health research program (UIDP/04462/2020) is also acknowledged to support J.M.Peritoneal membrane status, clinical data and aging-related molecules were investigated as predictors of long-term peritoneal dialysis (PD) outcomes. A 5-year prospective study was conducted with the following endpoints: (a) PD failure and time until PD failure, (b) major cardiovascular event (MACE) and time until MACE. A total of 58 incident patients with peritoneal biopsy at study baseline were included. Peritoneal membrane histomorphology and aging-related indicators were assessed before the start of PD and investigated as predictors of study endpoints. Fibrosis of the peritoneal membrane was associated with MACE occurrence and earlier MACE, but not with the patient or membrane survival. Serum α-Klotho bellow 742 pg/mL was related to the submesothelial thickness of the peritoneal membrane. This cutoff stratified the patients according to the risk of MACE and time until MACE. Uremic levels of galectin-3 were associated with PD failure and time until PD failure. This work unveils peritoneal membrane fibrosis as a window to the vulnerability of the cardiovascular system, whose mechanisms and links to biological aging need to be better investigated. Galectin-3 and α-Klotho are putative tools to tailor patient management in this home-based renal replacement therapy.publishersversionpublishe

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.This research received was founded by Fundación Renal Íñigo Álvarez de Toledo (FRIAT). The research groups of S.M.-F. and E.G.-P. are funded by the Ministerio de Economia, Industria y competitividad: FIS/Fondos FEDER (PI20/00487; PI21/01430). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Financiadores Fundación Renal Íñigo Álvarez de Toledo Ministerio de Economia Federación Española de Enfermedades Raras Spain PI21/0143

Longitudinal changes in adherence to the portfolio and DASH dietary patterns and cardiometabolic risk factors in the PREDIMED-Plus study

[Background & aims]: The Portfolio and Dietary Approaches to Stop Hypertension (DASH) diets have been shown to lower cardiometabolic risk factors in randomized controlled trials (RCTs). However, the Portfolio diet has only been assessed in RCTs of hyperlipidemic patients. Therefore, to assess the Portfolio diet in a population with metabolic syndrome (MetS), we conducted a longitudinal analysis of one-year data of changes in the Portfolio and DASH diet scores and their association with cardiometabolic risk factors in Prevención con Dieta Mediterránea (PREDIMED)-Plus trial. [Methods]: PREDIMED-Plus is an ongoing clinical trial (Trial registration: ISRCTN89898) conducted in Spain that includes 6874 older participants (mean age 65 y, 48% women) with overweight/obesity fulfilling at least three criteria for MetS. Data for this analysis were collected at baseline, six months and one year. Adherence to the Portfolio and DASH diet scores were derived from a validated 143-item food frequency questionnaire. We used linear mixed models to examine the associations of 1-SD increase and quartile changes in the diet scores with concomitant changes in cardiometabolic risk factors. [Results]: After adjusting for several potential confounders, a 1-SD increase in the Portfolio diet score was significantly associated with lower HbA1c (β [95% CI]: −0.02% [−0.02, −0.01], P < 0.001), fasting glucose (−0.47 mg/dL [−0.83, −0.11], P = 0.01), triglycerides (−1.29 mg/dL [−2.31, −0.28], P = 0.01), waist circumference (WC) (−0.51 cm [−0.59, −0.43], P < 0.001), and body mass index (BMI) (−0.17 kg/m2 [−0.19, −0.15], P < 0.001). A 1-SD increase in the DASH diet score was significantly associated with lower HbA1c (−0.03% [−0.04, −0.02], P < 0.001), glucose (−0.84 mg/dL [−1.18, −0.51], P < 0.001), triglycerides (−3.38 mg/dL [−4.37, −2.38], P < 0.001), non-HDL-cholesterol (−0.47 mg/dL [−0.91, −0.04], P = 0.03), WC (−0.69 cm [−0.76, −0.60 cm], P < 0.001), BMI (−0.25 kg/m2 [−0.28, −0.26 kg/m2], P < 0.001), systolic blood pressure (−0.57 mmHg [−0.81, −0.32 mmHg], P < 0.001), diastolic blood pressure (−0.15 mmHg [−0.29, −0.01 mmHg], P = 0.03), and with higher HDL-cholesterol (0.21 mg/dL [0.09, 0.34 mg/dL, P = 0.001]). Similar associations were seen when both diet scores were assessed as quartiles, comparing extreme categories of adherence. [Conclusions]: Among older adults at high cardiovascular risk with MetS, greater adherence to the Portfolio and DASH diets showed significant favourable prospective associations with several clinically relevant cardiometabolic risk factors. Both diets are likely beneficial for cardiometabolic risk reduction.The PREDIMED-Plus trial was supported by the Spanish government's official funding agency for biomedical research, ISCIII, through the Fondo de Investigación para la Salud (FIS) and co-funded by European Union ERDF/ESF, “A way to make Europe”/“Investing in your future” (five coordinated FIS projects led by JS-S and JVid, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183,PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, and PI19/01332), the Special Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to JS-S, the European Research Council (Advanced Research Grant 2014–2019, 340918) to MÁM-G, the Recercaixa Grant to JS-S (2013ACUP00194), grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018), a grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN grant, and funds from the European Regional Development Fund (CB06/03). This research was also partially funded by EU-H2020 Grant (EAT2BENICE/H2020-SFS-2016-2; Ref 728018). Study resulting from the SLT006/17/00246 grant, funded by the Department of Health of the Generalitat de Catalunya by the call “Acció instrumental de programes de recerca orientats en l'àmbit de la recerca i la innovació en salut”. We thank CERCA Programme/Generalitat de Catalunya for institutional support. This work is partially supported by ICREA under the ICREA Academia programme. IP-G receives a grant from the Spanish Ministry of Education, Culture and Sports (FPU 17/01925). MRBL was supported by “Miguel Servet Type I” program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER. AJG was supported by the Nora Martin Fellowship in Nutritional Sciences, the Banting & Best Diabetes Centre Tamarack Graduate Award in Diabetes Research, the Peterborough K.M. Hunter Charitable Foundation Graduate Award and an Ontario Graduate Scholarship. PH-A was supported by a postdoctoral fellowship (Juan de la Cierva-Formación), FJCI-2017–32205, funded by the Ministry of Science and Innovation. RE group has been supported by the ‘Ajut 2017-2021 SGR 1717 from the Generalitat de Catalunya. DJAJ was funded by the Government of Canada through the Canada Research Chair Endowment. JK was supported by the ‘FOLIUM’ programme within the FUTURMed project from the Fundación Instituto de Investigación Sanitaria Illes Balears (financed by 2017 annual plan of the sustainable tourism tax and at 50% with charge to the ESF Operational Program 2014–2020 of the Balearic Islands). JLS was funded by a Diabetes Canada Clinician Scientist Award

A sarcopenia index derived from malnutrition parameters in elderly haemodialysis patients

(1) Background: Persons with chronic kidney disease may have sarcopenia characterized by the loss of muscle mass and loss of muscle strength. However, EWGSOP2 criteria to diagnose sarcopenia are technically challenging, especially in elderly persons on hemodialysis. Sarcopenia may be associated with malnutrition. We aimed at defining a sarcopenia index derived from malnutrition parameters for use in elderly haemodialysis patients. (2) Methods: A retrospective study of 60 patients aged 75 to 95 years treated with chronic hemodialysis was conducted. Anthropometric and analytical variables, EWGSOP2 sarcopenia criteria and other nutrition-related variables were collected. Binomial logistic regressions were used to define the combination of anthropometric and nutritional parameters that best predict moderate or severe sarcopenia according to EWGSOP2, and performance for moderate and severe sarcopenia was assessed by the area under the curve (AUC) of receiver operating characteristic (ROC) curves. (3) Results: The combination of loss of strength, loss of muscle mass and low physical performance correlated with malnutrition. We developed regression-equation-related nutrition criteria that predicted moderate sarcopenia (elderly hemodialysis sarcopenia index-moderate, EHSI-M) and severe sarcopenia (EHSI-S) diagnosed according to EWGSOP2 with an AUC of 0.80 and 0.866, respectively. (4) Conclusions: There is a close relationship between nutrition and sarcopenia. The EHSI may identify EWGSOP2-diagnosed sarcopenia from easily accessible anthropometric and nutritional parameters.The authors would like to thank FRIAT for supporting the present study. The research groups of E.G.P., S.M.F. and A.O. are funded by the Ministerio de Economia, Industria y competitividad: FIS/Fondos FEDER (PI21/01430, PI16/01298, PI18/01386, PI19/00588, PI19/00815, PI20/00487, PI21/01240 and DTS18/00032), ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064, PERSTIGAN AC18/00071 and ISCIII-RETIC REDinREN RD016/0009) and Sociedad Española de Nefrología, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM. Financiadores Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM FRIAT Ministerio de Economia Sociedad Española de Nefrología Spain Federación Española de Enfermedades Raras Spain PI21/0143

Semaglutide Improves Liver Steatosis and De Novo Lipogenesis Markers in Obese and Type-2-Diabetic Mice with Metabolic-Dysfunction-Associated Steatotic Liver Disease

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a prevalent clinical condition associated with elevated morbidity and mortality rates. Patients with MASLD treated with semaglutide, a glucagon-like peptide-1 receptor agonist, demonstrate improvement in terms of liver damage. However, the mechanisms underlaying this beneficial effect are not yet fully elucidated. We investigated the efficacy of semaglutide in halting MASLD progression using a genetic mouse model of diabesity. Leptin-receptor-deficient mice with obesity and diabetes (BKS db/db) were either untreated or administered with semaglutide for 11 weeks. Changes in food and water intake, body weight and glycemia were monitored throughout the study. Body fat composition was assessed by dual-energy X-ray absorptiometry. Upon sacrifice, serum biochemical parameters, liver morphology, lipidomic profile and liver-lipid-related pathways were evaluated. The semaglutide-treated mice exhibited lower levels of glycemia, body weight, serum markers of liver dysfunction and total and percentage of fat mass compared to untreated db/db mice without a significant reduction in food intake. Histologically, semaglutide reduced hepatic steatosis, hepatocellular ballooning and intrahepatic triglycerides. Furthermore, the treatment ameliorated the hepatic expression of de novo lipogenesis markers and modified lipid composition by increasing the amount of polyunsaturated fatty acids. The administration of semaglutide to leptin-receptor-deficient, hyperphagic and diabetic mice resulted in the amelioration of MASLD, likely independently of daily caloric intake, suggesting a direct effect of semaglutide on the liver through modulation of the lipid profile