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Introduction and Objectives: The new recommendations suggesting changing the current nomenclature from Non-Alcoholic Fatty Liver Disease (NAFLD) to Metabolic associated fatty liver disease (MAFLD) are primarily aimed at improving the understanding of the disease. MAFLD is a hepatic manifestation of metabolic syndrome and is usually associated with obesity and type 2 diabetes, excluding other causes not associated with positive energy balance. This study aimed to characterize the pathophysiological mechanism involved in MAFLD development in susceptible-strain Black Tan and brachyuric (BTBR) insulin-resistant mice in combination with leptin deficiency (ob/ob). Materials and Methods: We studied liver morphology and biochemistry on our diabetic and obese mice model (BTBR ob/ob) as well as a diabetic non-obese control (BTBR + streptozotocin) and non-diabetic control mice (BTBR wild type) from 4-22 weeks. The lipid composition was assessed and lipid-related pathways were studied at transcriptional and protein levels. Results: Microvesicular steatosis was evident in BTBR ob/ob from week 6, progressing to macrovesicular in the following weeks. At the 12th week, inflammatory clusters, activation of STAT3 and Nrf2 signaling pathways, and hepatocellular ballooning. At 22 weeks, the histopathological features previously observed were maintained and no signs of fibrosis were detected. Liver gene-expression analysis demonstrated modifications in fatty acid transporters associated with uptake (Cd36, Cd204, Fatp4)/efflux (Abca1, Abcg1), de novo fatty acid synthesis enzymes (ACC, FASN, SCD-1) and transcription factors related to lipogenic pathways (Pparα/γ, Srebp-1, Chrebp-1). Additionally, the lipidomic analysis showed profiles associated with de novo lipogenesis (DNL), showing a significant increase in palmitic acid (C16:0), palmitoleic acid (C16:1n7) and oleic acid (C18:1n9). Conclusions: BTBR ob/ob mice develop MAFLD profiles that resemble pathological features observed in humans, with overactivation of inflammatory response, oxidative stress and DNL signaling pathways. Therefore, BTBR ob/ob mouse is an excellent model for the study of the steatosis to steatohepatitis transition.

Diabetic nephropathy (DN) is the main leading cause of chronic kidney disease worldwide. Although remarkable therapeutic advances have been made during the last few years, there still exists a high residual risk of disease progression to end-stage renal failure. To further understand the pathogenesis of tissue injury in this disease, by means of the Next-Generation Sequencing, we have studied the microRNA (miRNA) differential expression pattern in kidneys of Black and Tan Brachyury (BTBR) ob/ob (leptin deficiency mutation) mouse. This experimental model of type 2 diabetes and obesity recapitulates the key histopathological features described in advanced human DN and therefore can provide potential useful translational information. The miRNA-seq analysis, performed in the renal cortex of 22-week-old BTBR ob/ob mice, pointed out a set of 99 miRNAs significantly increased compared to non-diabetic, non-obese control mice of the same age, whereas no miRNAs were significantly decreased. Among them, miR-802, miR-34a, miR-132, miR-101a, and mir-379 were the most upregulated ones in diabetic kidneys. The in silico prediction of potential targets for the 99 miRNAs highlighted inflammatory and immune processes, as the most relevant pathways, emphasizing the importance of inflammation in the pathogenesis of kidney damage associated to diabetes. Other identified top canonical pathways were adipogenesis (related with ectopic fatty accumulation), necroptosis (an inflammatory and regulated form of cell death), and epithelial-to-mesenchymal transition, the latter supporting the importance of tubular cell phenotype changes in the pathogenesis of DN. These findings could facilitate a better understanding of this complex disease and potentially open new avenues for the design of novel therapeutic approaches to DN.

Sarcopenia and dynapenia are two terms associated with ageing that respectively define the loss of muscle mass and strength. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) introduced the EWGSOP2 diagnostic algorithm for sarcopenia, which integrates both concepts. It consists of 4 sequential steps: screening for sarcopenia, examination of muscle strength, assessment of muscle mass and physical performance; depending on these last 3 aspects sarcopenia is categorised as probable, confirmed, and severe respectively. In the absence of validation of the EWGSOP2 algorithm in various clinical contexts, its use in haemodialysis poses several limitations: (a) low sensitivity of the screening, (b) the techniques that assess muscle mass are not very accessible, reliable, or safe in routine clinical care, (c) the sequential use of the magnitudes that assess dynapenia and muscle mass do not seem to adequately reflect the muscular pathology of the elderly person on dialysis. We reflect on the definition of sarcopenia and the use of more precise terms such as “myopenia” (replacing the classic concept of sarcopenia to designate loss of muscle mass), dynapenia and kratopenia. Prospective evaluation of EWGSOP2 and its comparison with alternatives (i.e. assessment of kratopenia and dynapenia only; steps 2 and 4) is proposed in terms of its applicability in clinical routine, resource consumption, identification of at-risk individuals and impact on events. Resumen: Sarcopenia y dinapenia son dos términos asociados al envejecimiento que definen respectivamente la pérdida de masa y de fuerza muscular. En el año 2019, el European Working Groupon Sarcopenia in Older People (EWGSOP) introdujo el algoritmo diagnóstico EWGSOP2 de sarcopenia, que integra ambos conceptos. Consiste en 4 pasos secuenciales: cribado de sarcopenia, exploración de la fuerza muscular, evaluación de la masa muscular y de su rendimiento físico; dependiendo de estos 3 últimos aspectos la sarcopenia se categoriza como probable, confirmada y grave respectivamente. A falta de validación del algoritmo EWGSOP2 en diversos contextos clínicos, su utilización en hemodiálisis plantea diversas limitaciones: (a) poca sensibilidad del cribado, (b) las técnicas que evalúan la masa muscular son poco accesibles, fiables o seguras en la rutina clínica asistencial, (c) el uso secuencial de las magnitudes que evalúan la dinapenia y la masa muscular no parecen reflejar adecuadamente la patología muscular del anciano en diálisis. Reflexionamos sobre la definición de sarcopenia y la utilización de términos más precisos como “miopenia” (sustituyendo al concepto clásico de sarcopenia para designar la pérdida de masa muscular), dinapenia y kratopenia. Se propone la evaluación prospectiva del EWGSOP2 y su comparación con alternativas (ej. evaluación exclusiva de kratopenia y dinapenia; pasos 2 y 4) en cuanto a su aplicabilidad en la rutina clínica, consumo de recursos, identificación de personas en riesgo e impacto sobre eventos.

Abstract Background Frailty among older adults undergoing hemodialysis is increasingly prevalent, significantly impacting cognitive function, mobility, and social engagement. This study focuses on the clinical profiles of very older adults in hemodialysis, particularly examining the interplay of dependency and frailty, and their influence on dialysis regimens. Methods In this observational, descriptive study, 107 patients aged over 75 from four outpatient centers and one hospital unit were examined over a year. Patient data encompassed sociodemographic factors, dialysis specifics, analytical outcomes, lifestyle elements, and self-reported post-treatment fatigue. Malnutrition-inflammation scale was used to measure the Nutritional status; MIS scale for malnutrition-inflammation, Barthel index for dependency, Charlson comorbidity index; FRIED scale for frailty and the SF12 quality of life measure. Results The study unveiled that a substantial number of older adults on hemodialysis faced malnutrition (55%), dependency (21%), frailty (46%), and diminished quality of life (57%). Patients with dependency were distinctively marked by higher comorbidity, severe malnutrition, enhanced frailty, nursing home residency, dependency on ambulance transportation, and significantly limited mobility, with 77% unable to walk. Notably, 56% of participants experienced considerable post-dialysis fatigue, correlating with higher comorbidity, increased dependency, and poorer quality of life. Despite varying clinical conditions, dialysis patterns were consistent across the patient cohort. Conclusions The older adult cohort, averaging over four years on hemodialysis, exhibited high rates of comorbidity, frailty, and dependency, necessitating substantial support in transport and living arrangements. A third of these patients lacked residual urine output, yet their dialysis regimen mirrored those with preserved output. The study underscores the imperative for tailored therapeutic strategies to mitigate dependency, preserve residual renal function, and alleviate post-dialysis fatigue, ultimately enhancing the physical quality of life for these patients.

Resumen: Sarcopenia y dinapenia son dos términos asociados al envejecimiento que definen respectivamente la pérdida de masa y de fuerza muscular. En el año 2019, el European Working Groupon Sarcopenia in Older People (EWGSOP) introdujo el algoritmo diagnóstico EWGSOP2 de sarcopenia, que integra ambos conceptos. Consiste en cuatro pasos secuenciales: cribado de sarcopenia, exploración de la fuerza muscular, evaluación de la masa muscular y de su rendimiento físico; dependiendo de estos tres últimos aspectos la sarcopenia se categoriza como probable, confirmada y grave, respectivamente. A falta de validación del algoritmo EWGSOP2 en diversos contextos clínicos, su utilización en hemodiálisis (HD) plantea diversas limitaciones: a) poca sensibilidad del cribado, b) las técnicas que evalúan la masa muscular son poco accesibles, fiables o seguras en la rutina clínica asistencial y c) el uso secuencial de las magnitudes que evalúan la dinapenia y la masa muscular no parecen reflejar adecuadamente la patología muscular del paciente geriátrico en diálisis. Reflexionamos sobre la definición de sarcopenia y la utilización de términos más precisos como «miopenia» (sustituyendo al concepto clásico de sarcopenia para designar la pérdida de masa muscular), dinapenia y kratopenia. Se propone la evaluación prospectiva del EWGSOP2 y su comparación con alternativas (p. ej. evaluación exclusiva de kratopenia y dinapenia; pasos 2 y 4) en cuanto a su aplicabilidad en la rutina clínica, consumo de recursos, identificación de personas en riesgo e impacto sobre eventos. Abstract: Sarcopenia and dynapenia are two terms associated with ageing that respectively define the loss of muscle mass and strength. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) introduced the EWGSOP2 diagnostic algorithm for sarcopenia, which integrates both concepts. It consists of four sequential steps: screening for sarcopenia, examination of muscle strength, assessment of muscle mass and physical performance; depending on these last three aspects sarcopenia is categorised as probable, confirmed, and severe respectively. In the absence of validation of the EWGSOP2 algorithm in various clinical contexts, its use in haemodialysis poses several limitations: (a) low sensitivity of the screening, (b) the techniques that assess muscle mass are not very accessible, reliable, or safe in routine clinical care, (c) the sequential use of the magnitudes that assess dynapenia and muscle mass do not seem to adequately reflect the muscular pathology of the elderly person on dialysis. We reflect on the definition of sarcopenia and the use of more precise terms such as “myopenia” (replacing the classic concept of sarcopenia to designate loss of muscle mass), dynapenia and kratopenia. Prospective evaluation of EWGSOP2 and its comparison with alternatives (i.e. assessment of kratopenia and dynapenia only; steps 2 and 4) is proposed in terms of its applicability in clinical routine, resource consumption, identification of at-risk individuals and impact on events.

Background: CKD is a risk factor for severe COVID-19. However, the clinical spectrum of COVID-19 in hemodialysis patients is still poorly characterized. Objective: To analyze the clinical spectrum of COVID-19 on hemodialysis patients. Method: A retrospective observational study was conducted on 66 hemodialysis patients. Nasopharyngeal swab PCR and serology for SARS-CoV-2, blood analysis, chest radiography, treatment, and outcomes were assessed. Results: COVID-19 was diagnosed in 50 patients: 38 (76%) were PCR-positive and 12 (24%) were PCR-negative but developed anti-SARS-CoV-2 antibodies. By contrast, 17% of PCR-positive patients failed to develop detectable antibodies against SARS-CoV-2. Among PCR-positive patients, 5/38 (13%) were asymptomatic, while among PCR-negative patients 7/12 (58%) were asymptomatic (p = 0.005) for a total of 12/50 (24%) asymptomatic patients. No other differences were found between PCR-positive and PCR-negative patients. No differences in potential predisposing factors were found between asymptomatic and symptomatic patients except for a lower use of ACE inhibitors among asymptomatic patients. Asymptomatic patients had laboratory evidence of milder disease such as higher lymphocyte counts and oxygen saturation and lower troponin I and interleukin-6 levels than symptomatic patients. Overall mortality was 7/50 (14%) and occurred only in symptomatic PCR-positive patients in whom mortality was 7/33 (21%). Conclusions: Asymptomatic SARS-CoV-2 infection is common in hemodialysis patients, especially among patients with initial negative PCR that later seroconvert. Thus COVID-19 mortality in hemodialysis patients may be lower than previously estimated based on PCR tests alone.

BackgroundIn 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.MethodsProspective 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).ResultsThe 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).ConclusionsAccording 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.