RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Real-world data on the effectiveness and safety of teriflunomide in patients with relapsing–remitting multiple sclerosis: The EFFECT study

Introduction: The objective of the present study was to evaluate the effectiveness and safety of teriflunomide in relapsing–remitting multiple sclerosis (RRMS) patients treated in a real-world setting. Methods: This retrospective study was conducted at neurology departments of 15 hospitals in 2 Spanish Autonomous Regions. The primary endpoint was annualized relapse rate (ARR) during teriflunomide treatment. Secondary endpoints included changes in Expanded Disability Status Scale (EDSS), radiological activity, and adverse events (AEs). Results: 485 patients (72.2% women, mean of 36.5 years) were included; 74.8% had previously received other disease-modifying treatment. EDSS score at inclusion was 2.0. Mean time receiving teriflunomide was 2.5 years. The ARR during teriflunomide treatment was 0.16, a 20% lower than at baseline (0.20), although the difference did not reach statistical significance (P = 0.098). The mean number of relapses significantly decreased after teriflunomide initiation, with 0.17 relapses at month 12, 0.11 at month 24, and 0.13 at month 36, compared to 0.50 in the year before teriflunomide initiation (P < 0.001). EDSS scores were maintained over the study period. The percentage of patients without gadolinium-enhanced T1-weighted lesions was significantly higher after teriflunomide (P = 0.01), and the percentage of patients without new/enlarged lesions on T2 remained stable. The proportion of patients with AEs was 41.9% (1.4% serious), being hair thinning (19.4%) and gastrointestinal disorders (18.4%) the most frequent. Discussion: Over teriflunomide treatment, the ARR was low, radiologic evidence of disease activity decreased, and disability stabilized. These findings, together with the acceptable safety profile observed, support the use of teriflunomide in RRMS patients. Resumen: Introducción: El objetivo de este estudio es evaluar la efectividad y seguridad de teriflunomida en pacientes con esclerosis múltiple remitente-recurrente (EMRR) en un contexto del mundo real. Métodos: Realizamos un estudio retrospectivo de pacientes atendidos en los servicios de neurología de 15 hospitales localizados en dos comunidades autónomas de España. La variable principal fue la tasa anualizada de brotes (TAB) durante el tratamiento con teriflunomida. Como variables secundarias analizamos los cambios en la puntuación de la escala Expanded Disability Status Scale (EDSS), la actividad radiológica y los efectos adversos. Resultados: Nuestra muestra incluyó 485 pacientes (72,2% mujeres; edad media de 36,5 años); 74,8% de los pacientes habían recibido otro tratamiento modificador de la enfermedad con anterioridad. La puntuación media en la EDSS al inicio fue de 2,0. Los pacientes recibieron teriflunomida durante una media de 2,5 años. Durante el tratamiento, la TAB se redujo en un 20% respecto al inicio (0,16 frente a 0,20), aunque la diferencia no fue estadísticamente significativa (P = 0,098). El número medio de brotes se redujo significativamente tras iniciar el tratamiento con teriflunomida, pasando de 0,50 brotes en el año anterior al inicio del estudio a 0,17 brotes a los 12 meses de tratamiento, 0,11 brotes a los 24 meses y 0,13 brotes a los 36 meses (p < 0,001). Las puntuaciones en la EDSS se mantuvieron estables a lo largo del estudio. El porcentaje de pacientes que no mostraron lesiones captadoras de gadolinio en secuencias potenciadas en T1 fue significativamente mayor tras el tratamiento con teriflunomida (p = 0,01), mientras que el porcentaje de pacientes que no presentaron lesiones nuevas o un aumento en el tamaño de lesiones previas en secuencias potenciadas en T2 permaneció estable. Se reportaron efectos adversos en 41,9% de los pacientes (graves en 1,4%); los más frecuentes fueron la pérdida de cabello (19,4%) y los problemas gastrointestinales (18,4%). Conclusión: Durante el periodo de tratamiento con teriflunomida, la TAB y la actividad radiológica de la enfermedad disminuyeron, mientras que el grado de discapacidad permaneció estable. Estos hallazgos, junto con el aceptable perfil de seguridad de teriflunomida, apoyan el uso del fármaco en pacientes con EMRR

Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico

10.1038/nature12828Nature506748697-101NATU

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. © 2022, The Author(s)