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

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Comparação entre a técnica de substituição do ligamento redondo por implante de fascia lata bubalina preservada em glicerina e o uso de pino transarticular na redução e na estabilização da luxação coxofemoral experimentalmente induzida em cães Comparation between the technique of substitution of the round ligamentum by glycerin-preserved bubaline fascia lata implant and the use of transarticular pin in the redution and stabilization of experimentally induzed coxofemoral luxation in dogs

Compararam-se duas técnicas cirúrgicas de redução e estabilização da articulação coxofemoral experimentalmente luxada em cães. Dois grupos de animais, submetidos às respectivas técnicas após a indução cirúrgica da luxação, foram acompanhados clínica e radiograficamente por um período de 60 dias, findos os quais, realizaram-se avaliações macroscópica e histológica e teste de tensiometria das articulações. Cada grupo foi constituído por oito animais, clinicamente sadios, com pesos entre 5 e 20kg. Os animais submetidos ao implante de fáscia apresentaram, ao exame físico, evolução da deambulação significativamente precoce em relação aos do grupo submetido ao implante de pino de Steinmann, além de menor grau de atrofia muscular. Os testes de tensiometria, as avaliações macroscópicas e radiográficas e os exames histológicos não diferiram entre os grupos, evidenciando também que ambas as técnicas não geraram alterações deletérias à articulação operada. Conclui-se que a técnica de estabilização da articulação coxofemoral com implante de fascia lata foi clinicamente eficaz e vantajosa quando comparada à técnica do pino transarticular.<br>It was compared both surgical techniques of reduction and stabilization of experimentally luxated coxofemoral join in dog. Two groups were submitted to the techniques after surgical induction of the luxation. All animals were clinically and radiografically observed during 60 days. After that, a macroscopic study, an histological exam, and a tensiometry test in the articulations were performed. Each group had eight healthy animals, weighting from 5 to 20kg. The most important advantage was related to the deambulation, which the animals submited to the facia lata implant showed a faster evolution after the surgery at the physical exam, and muscular atrophy in a smaller degree. The tensiometry tests, the radiographic and the histological exams did not present important differences between both groups, but they were useful to show that the two techniques did not cause alterations in the studied articulation. It can be concluded that the stabilization of the coxofemoral articulation using bubaline fascia lata implant was clinically efficient and more advantageous compared to the transarticular pin technique