Effect of Immunosuppressive Treatments on Kidney Outcomes After Gross Hematuria-Related Acute Kidney Injury in Older Patients With IgA Nephropathy.

Introduction: Macroscopic hematuria (MH) bouts, frequently accompanied by acute kidney injury (AKI-MH) are one of the most common presentations of IgA nephropathy (IgAN) in the elderly. Immunosuppressive therapies are used in clinical practice; however, no studies have analyzed their efficacy on kidney outcomes. Methods: This is a retrospective, multicenter study of a cohort of patients aged ≥50 years with biopsy-proven IgAN presenting with AKI-MH. Outcomes were complete, partial, or no recovery of kidney function at 1 year after AKI-MH, and kidney survival at 1, 2, and 5 years. Propensity score matching (PSM) analysis was applied to balance baseline differences between patients treated with immunosuppression and those not treated with immunosuppression. Results: The study group consisted of 91 patients with a mean age of 65 ± 15 years, with a mean follow-up of 59 ± 36 months. Intratubular red blood cell (RBC) casts and acute tubular necrosis were found in all kidney biopsies. The frequency of endocapillary hypercellularity and crescents were low. Immunosuppressive therapies (corticosteroids alone or combined with mycophenolate mofetil or cyclophosphamide) were prescribed in 52 (57%) patients, whereas 39 (43%) received conservative treatment. There were no significant differences in the proportion of patients with complete, partial, or no recovery of kidney function at 1 year between patients treated with immunosuppression and those not treated with immunosuppression (29% vs. 36%, 30.8% vs. 20.5% and 40.4 % vs. 43.6%, respectively). Kidney survival at 1, 3, and 5 years was similar among treated and untreated patients (85% vs. 81%, 77% vs. 76% and 72% vs. 66%, respectively). Despite the PSM analysis, no significant differences were observed in kidney survival between the two groups. Fourteen patients (27%) treated with immunosuppression had serious adverse events. Conclusions: Immunosuppressive treatments do not modify the unfavorable prognosis of patients with IgAN who are aged ≥50 years presenting with AKI-MH, and are frequently associated with severe complications.

Extremely Differentiated T Cell Subsets Contribute to Tissue Deterioration During Aging.

There is a dramatic remodeling of the T cell compartment during aging. The most notorious changes are the reduction of the naive T cell pool and the accumulation of memory-like T cells. Memory-like T cells in older people acquire a phenotype of terminally differentiated cells, lose the expression of costimulatory molecules, and acquire properties of senescent cells. In this review, we focus on the different subsets of age-associated T cells that accumulate during aging. These subsets include extremely cytotoxic T cells with natural killer properties, exhausted T cells with altered cytokine production, and regulatory T cells that gain proinflammatory features. Importantly, all of these subsets lose their lymph node homing capacity and migrate preferentially to nonlymphoid tissues, where they contribute to tissue deterioration and inflammaging.

Electronic Patient-Reported Outcomes in Nephrology: Focus on Hemodialysis.

The success of hemodialysis (HD) treatments has been evaluated using objective measures of analytical parameters, or machine-measured parameters, despite having available validated instruments that assess patient perspective. There is an emerging interest regarding the use and relevance of patient-related outcomes (PROs). Electronic PROs (ePROs) involve the use of electronic technology, provide rapid access to this information, and are becoming more widely used in clinical trials and studies to evaluate efficacy and safety. Despite the scarce literature, this review suggests that ePROs are useful in providing a more customized and multidimensional approach to patient management and in making better clinical decisions in relevant aspects such as vascular access, duration and frequency of dialysis sessions, treatment of anemia, mental health, fatigue, and quality of life. The purpose of this review is to raise interest in the systematic use of ePROs in HD and to promote the development of studies in this field, which can respond to the gaps in knowledge and contribute to the implementation of the use of ePROs through new technologies, helping to improve the quality of health care.

Nicotinamide adenine dinucleotide metabolism in the immune response, autoimmunity and inflammageing.

Metabolism is dynamically regulated to accompany immune cell function, and altered immunometabolism can result in impaired immune responses. Concomitantly, the pharmacological manipulation of metabolic processes offers an opportunity for therapeutic intervention in inflammatory disorders. The nicotinamide adenine dinucleotide (NAD+ ) is a critical metabolic intermediate that serves as enzyme cofactor in redox reactions, and is also used as a co-substrate by many enzymes such as sirtuins, adenosine diphosphate ribose transferases and synthases. Through these activities, NAD+ metabolism regulates a broad spectrum of cellular functions such as energy metabolism, DNA repair, regulation of the epigenetic landscape and inflammation. Thus, the manipulation of NAD+ availability using pharmacological compounds such as NAD+ precursors can have immune-modulatory properties in inflammation. Here, we discuss how the NAD+ metabolism contributes to the immune response and inflammatory conditions, with a special focus on multiple sclerosis, inflammatory bowel diseases and inflammageing. LINKED ARTICLES: This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.

The role of T cells in age-related diseases.

Age-related T cell dysfunction can lead to failure of immune tolerance mechanisms, resulting in aberrant T cell-driven cytokine and cytotoxic responses that ultimately cause tissue damage. In this Review, we discuss the role of T cells in the onset and progression of age-associated conditions, focusing on cardiovascular disorders, metabolic dysfunction, neuroinflammation and defective tissue repair and regeneration. We present different mechanisms by which T cells contribute to inflammageing and might act as modulators of age-associated diseases, including through enhanced pro-inflammatory and cytotoxic activity, defective clearance of senescent cells or regulation of the gut microbiota. Finally, we propose that 'resetting' immune system tolerance or targeting pathogenic T cells could open up new therapeutic opportunities to boost resilience to age-related diseases.

Reflexiones sobre la necesidad de Unidades de Referencia de Nefropatología / Reflections on the need for Nephropathology Reference Units

1. La ERC tiene una elevada incidencia y prevalencia con un alto impacto sobre la calidad de vida y mortalidad de los pacientes, lo que supone un importante consumo de recursos sanitarios. 2. En un porcentaje relevante de pacientes no se dispone de un diagnóstico etiológico de la ERC, lo que limita sus posibilidades de tratamiento y curación. 3. Las acciones dirigidas a mejorar el diagnóstico permitirán favorecer un mejor conocimiento de las causas de la ERC y optimizar el tratamiento. 4. La biopsia renal, constituye el procedimiento necesario para el estudio histopatológico del tejido renal que permitirá establecer el diagnóstico, las posibilidades de tratamiento y el pronóstico del daño renal. 5. El trasplante renal constituye la mejor opción de TRS. La causa más frecuente de pérdida del injerto renal es el rechazo. La biopsia renal es el único método para establecer el tipo de rechazo e iniciar el tratamiento más adecuado. 6. La planificación del tratamiento de la enfermedad renal se establece con base en un diagnóstico preciso y este se basa en el diagnóstico histológico. La falta de una adecuada interpretación diagnóstica, bien por inexperiencia del patólogo, bien por falta de medios diagnósticos (microscopia electrónica), condiciona y limita las opciones de tratamiento en perjuicio del enfermo

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Impacto de la pandemia COVID-19 en los servicios de Nefrología españoles / Impact of the COVID-19 pandemic on Spanish Nephrology Services

La pandemia de la infección por el coronavirus tipo2 del síndrome respiratorio agudo grave o SARS-CoV-2, causante de la enfermedad por coronavirus de 2019 (COVID-19), ha precisado una transformación drástica de los hospitales y, por consiguiente, de los servicios de Nefrología de España. Desde la Sociedad Española de Nefrología se ha realizado una encuesta a los jefes de servicios de Nefrología de España abordando la reorganización de los servicios de Nefrología y la actividad en la época de mayor afectación por COVID-19. Hemos preguntado por la integración de los nefrólogos en equipos COVID-19, la actividad asistencial de hospitalización de Nefrología (ingresos programados, biopsias renales), la realización de cirugías programadas como los accesos vasculares o la implantación de catéteres peritoneales, la suspensión o no del programa de trasplante renal y la transformación de las consultas externas de Nefrología. En el trabajo actual se detallan la adaptación y la transformación de los servicios de Nefrología en la pandemia COVID-19 en España. Durante dicho periodo se han suspendido los ingresos programados en los servicios de Nefrología, la realización de cirugías/biopsias programadas y ha disminuido en más de un 75% el programa de trasplante renal. Es de interés mencionar que las consultas externas de Nefrología se han realizado mayoritariamente telefónicamente. En conclusión, la pandemia ha impactado claramente en la actividad clínica en los servicios de Nefrología españoles disminuyendo la actividad programada y los trasplantes renales y modificando la actividad en consultas externas. Un plan de transformación asistencial e implementación de telemedicina en Nefrología parece necesario y de gran utilidad en un futuro próximo

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has required a rapid and drastic transformation of hospitals, and consequently also of Spanish Nephrology Units, to respond to the critical situation. The Spanish Society of Nephrology conducted a survey directed to the Heads of Nephrology Departments in Spain that addressed the reorganisation of Nephrology departments and activity during the peak of COVID-19 pandemic. The survey has been focused on the integration of nephrologists in COVID-19 teams, nephrology inpatient care activities (elective admissions, kidney biopsies), the performance of elective surgeries such as vascular accesses or implantation of peritoneal catheters, the suspension of kidney transplantation programmes and the transformation of nephrology outpatient clinics. This work details the adaptation and transformation of nephrology services during the COVID-19 pandemic in Spain. During this period, elective admissions to Nephrology Services, elective surgeries and biopsies were suspended, and the kidney transplant programme was scaled back by more than 75%. It is worth noting that outpatient nephrology consultations were carried out largely by telephone. In conclusion, the pandemic has clearly impacted clinical activity in Spanish Nephrology departments, reducing elective activity and kidney transplants, and modifying activity in outpatient clinics. A restructuring and implementation plan in Nephrology focused on telemedicine and/or virtual medicine would seem to be both necessary and very useful in the near future

[Impact of the COVID-19 pandemic on Spanish Nephrology Services]. / Impacto de la pandemia COVID-19 en los servicios de Nefrología españoles.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has required a rapid and drastic transformation of hospitals, and consequently also of Spanish Nephrology Units, to respond to the critical situation. The Spanish Society of Nephrology conducted a survey directed to the Heads of Nephrology Departments in Spain that addressed the reorganisation of Nephrology departments and activity during the peak of COVID-19 pandemic. The survey has been focused on the integration of nephrologists in COVID-19 teams, nephrology inpatient care activities (elective admissions, kidney biopsies), the performance of elective surgeries such as vascular accesses or implantation of peritoneal catheters, the suspension of kidney transplantation programmes and the transformation of nephrology outpatient clinics. This work details the adaptation and transformation of nephrology services during the COVID-19 pandemic in Spain. During this period, elective admissions to Nephrology Services, elective surgeries and biopsies were suspended, and the kidney transplant programme was scaled back by more than 75%. It is worth noting that outpatient nephrology consultations were carried out largely by telephone. In conclusion, the pandemic has clearly impacted clinical activity in Spanish Nephrology departments, reducing elective activity and kidney transplants, and modifying activity in outpatient clinics. A restructuring and implementation plan in Nephrology focused on telemedicine and/or virtual medicine would seem to be both necessary and very useful in the near future.

Situación de la infección por SARS-CoV-2 en pacientes en tratamiento renal sustitutivo Informe del Registro COVID-19 de la Sociedad Española de Nefrología (S.E.N.) / SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (S.E.N.)

La reciente aparición de la pandemia por el coronavirus SARS-CoV-2 ha impactado de forma muy importante en la población general. Los pacientes en tratamiento renal sustitutivo (TRS) no han sido ajenos a esta situación y por sus características resultan especialmente vulnerables. Presentamos los resultados del análisis del Registro COVID-19 de la S.E.N. MATERIAL Y MÉTODOS: EL Registro comenzó a funcionar el 18 de marzo de 2020. Recoge variables epidemiológicas, datos del contagio y diagnóstico, clínica acompañante, tratamientos y desenlace. Se trata de un registro "on line". Los pacientes fueron diagnosticados de infección por SARS-Cov-2 en base a los resultados de la PCR del virus, realizada tanto en pacientes que habían manifestado clínica compatible o tenían signos sospechosos como en aquellos a los que se había hecho como cribado tras algún contacto conocido con otro enfermo. RESULTADOS: A fecha 11 de abril el Registro disponía de datos de 868 pacientes, procedentes de todas las Comunidades Autónomas. La modalidad de TRS más representada es la hemodiálisis en centro (HDC) seguida de los pacientes trasplantados. La clínica de presentación es similar a la población general. Un porcentaje muy elevado (85%) requirió ingreso hospitalario, un 8% en unidades de cuidados intensivos. Los tratamientos más utilizados fueron hidroxicloroquina, lopinavirritonavir y esteroides. La mortalidad es elevada y alcanza el 23%: los pacientes fallecidos estaban con más frecuencia en HDC, desarrollaban más frecuentemente neumonía y recibían en menos ocasiones lopinavir-ritonavir y esteroides. La edad y la neumonía se asociaban de forma independiente al riesgo de fallecer. CONCLUSIONES: La infección por SARS-CoV-2 afecta ya a un número importante de pacientes españoles en TRS, fundamentalmente aquellos que están en HDC, las tasas de hospitalización son muy elevadas y la mortalidad es elevada; la edad y el desarrollo de neumonía son factores asociados a mortalidad

The recent appearance of the SARS-CoV-2 coronavirus pandemic has had a significant impact on the general population. Patients on renal replacement therapy (RRT) have not been unaware of this situation and due to their characteristics they are especially vulnerable. We present the results of the analysis of the COVID-19 Registry of the Spanish Society of Nephrology. MATERIAL AND METHODS: The Registry began operating on March 18th, 2020. It collects epidemiological variables, contagion and diagnosis data, signs and symptoms, treatments and outcomes. It is an "online" registry. Patients were diagnosed with SARS-Cov-2 infection based on the results of the PCR of the virus, carried out both in patients who had manifested compatible symptoms or had suspicious signs, as well as in those who had undergone screening after some contac, acquainted with another patient. RESULTS: As of April 11, the Registry had data on 868 patients, from all the Autonomous Communities. The most represented form of TRS is in-center hemodialysis (ICH) followed by transplant patients. Symptoms are similar to the general population. A very high percentage (85%) required hospital admission, 8% in intensive care units. The most used treatments were hydroxychloroquine, lopinavir-ritonavir, and steroids. Mortality is high and reaches 23%; deceased patients were more frequently on ICH, developed pneumonia more frequently, and received less frequently lopinavir-ritonavir and steroids. Age and pneumonia were independently associated with the risk of death. CONCLUSIONS: SARS-CoV-2 infection already affects a significant number of Spanish patients on RRT, mainly those on ICH, hospitalization rates are very high and mortality is high; age and the development of pneumonia are factors associated with mortality

Protocolo de actuación ante la epidemia de enfermedad por coronavirus en los pacientes de diálisis y trasplantados renales / Protocol against coronavirus diseases in patients on renal replacement therapy: Dialysis and kidney transplant

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[SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (SEN)]. / Situación de la infección por SARS-CoV-2 en pacientes en tratamiento renal sustitutivo. Informe del Registro COVID-19 de la Sociedad Española de Nefrología (SEN).

INTRODUCTION: The recent appearance of the SARS-CoV-2 coronavirus pandemic has had a significant impact on the general population. Patients on renal replacement therapy (RRT) have not been unaware of this situation and due to their characteristics they are especially vulnerable. We present the results of the analysis of the COVID-19 Registry of the Spanish Society of Nephrology. MATERIAL AND METHODS: The Registry began operating on March 18th, 2020. It collects epidemiological variables, contagion and diagnosis data, signs and symptoms, treatments and outcomes. It is an online registry. Patients were diagnosed with SARS-CoV-2 infection based on the results of the PCR of the virus, carried out both in patients who had manifested compatible symptoms or had suspicious signs, as well as in those who had undergone screening after some contact acquainted with another patient. RESULTS: As of April 11, the Registry had data on 868 patients, from all the Autonomous Communities. The most represented form of RRT is in-center hemodialysis (ICH) followed by transplant patients. Symptoms are similar to the general population. A very high percentage (85%) required hospital admission, 8% in intensive care units. The most used treatments were hydroxychloroquine, lopinavir-ritonavir, and steroids. Mortality is high and reaches 23%; deceased patients were more frequently on ICH, developed pneumonia more frequently, and received less frequently lopinavir-ritonavir and steroids. Age and pneumonia were independently associated with the risk of death. CONCLUSIONS: SARS-CoV-2 infection already affects a significant number of Spanish patients on RRT, mainly those on ICH, hospitalization rates are very high and mortality is high; age and the development of pneumonia are factors associated with mortality.

2S albumins and nsLTP are involved in anaphylaxis to pizza sauce: IgE recognition before and after allergen processing.

Although pizza is one of the most popular foods in the world, allergic responses after ingesting pizza are relatively uncommon. However, precisely identifying the allergens responsible for these allergic reactions is challenging because of the high and diverse number of ingredients used in pizza preparation. In this report, we aim to identify the allergens responsible for systemic allergic reactions following ingestion of pizza in two patients. Using a skin prick by prick test (SPPT) and in vitro techniques, with natural and recombinant purified allergens from tomato and mustard seeds, we identified 2S albumin and non-specific lipid transfer proteins (nsLTP) as the proteins involved. However, IgE responses to the four nsLTPs differed before and after denaturation and reduction, thus suggesting additional complexity around nsLTP in food processing.

Glycolysis - a key player in the inflammatory response.

The inflammatory response involves the activation of several cell types to fight insults caused by a plethora of agents, and to maintain the tissue homoeostasis. On the one hand, cells involved in the pro-inflammatory response, such as inflammatory M1 macrophages, Th1 and Th17 lymphocytes or activated microglia, must rapidly provide energy to fuel inflammation, which is essentially accomplished by glycolysis and high lactate production. On the other hand, regulatory T cells or M2 macrophages, which are involved in immune regulation and resolution of inflammation, preferentially use fatty acid oxidation through the TCA cycle as a main source for energy production. Here, we discuss the impact of glycolytic metabolism at the different steps of the inflammatory response. Finally, we review a wide variety of molecular mechanisms which could explain the relationship between glycolytic metabolites and the pro-inflammatory phenotype, including signalling events, epigenetic remodelling, post-transcriptional regulation and post-translational modifications. Inflammatory processes are a common feature of many age-associated diseases, such as cardiovascular and neurodegenerative disorders. The finding that immunometabolism could be a master regulator of inflammation broadens the avenue for treating inflammation-related pathologies through the manipulation of the vascular and immune cell metabolism.