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

La cuarta fase de deformación hercínica en la zona centroibérica del Macizo Hespérico

[Resumen] Se define una cuarta fase de denominación hercínica de alcance regional aunque i- rregularmente desarroll ada, en vari os sectores de 1a zona Centroibérica a partir de un estudio de diversos elementos estructurales que presentan características semejantes. - En base a una correlación de los acontecimientos principales de la Orogenía Hercínica, situamos esta fase de deformación con posterioridad al desarrollo de las tres fases tectogenética principales reconocidas y con anterioridad al emplazamiento de los granitoides tardihercínicos y a otros fenómenos significativos ligados al ciclo hercínico. Esta cuarta fase genera estructuras a nivel macroscópico (pliegues hectométricos y cambios locales de la orientación regional de las direcciones estructura1es anteri ores) y mesoscópicos (p1iegues suaves de escala métrica y pl iegues angulosos de escala centimétrica); localmente produce esqulstosidad de fractura y de "strain-sli p". - La orientación principal de esta fase es N10E-N30E, si bien varía progresivamente en el sector oriental del Sistema Central hasta alcanzar direcciones de N90E-N100E. Esta variación es de la misma magnitud que las experimentadas por 1as direcciones estructural es de 1as fases hercín i cas anteriores, por lo que podría estar originada por el movimiento y rotación de bloques ligado a la fracturación tardihercínica.[Abstract] The study of structural elements in several areas of the Centrolberian zone support the existence of a forth deformation(F4) regionally developed. According with a correlation based on the main events during the Hercini an orogeny, these F4 may be chrono1og i ca 11 y P1aced after the three main deformation phases usually recognized and before 1ate-hercinyan gran it i crocks emplacement and also before other signifiicative hercinyan events. The F4 gives rise to macroscopic structures (hectometric fol ds and orientation changes of older structures) and mesoscopic structures(open metric folds and centrimetric chevron folds); locally produces fractura and strain-slip schistosity. The orientation of F4 structures is nearing N10E-N30E, altough changes progressively on the oriental zone of the Sistema Central until N90E-N100E. This change is similar to the variation of older structures; there before could be arised by the movement and rotation of blocks by late-hercinyan fractures

Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial

Background: The CRASH-3 trial hypothesised that timely tranexamic acid (TXA) treatment might reduce deaths from intracranial bleeding after traumatic brain injury (TBI). To explore the mechanism of action of TXA in TBI, we examined the timing of its effect on death. Methods: The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with a GCS score of 3 or bilateral unreactive pupils, stratified by severity and country income. We pool data from the CRASH-2 and CRASH-3 trials in a one-step fixed effects individual patient data meta-analysis. Results: There were 7637 patients for analysis after excluding patients with a GCS score of 3 or bilateral unreactive pupils. Of 1112 deaths, 23.3% were within 24 h of injury (early deaths). The risk of early death was reduced with TXA (112 (2.9%) TXA group vs 147 (3.9%) placebo group; risk ratio [RR] RR 0.74, 95% CI 0.58–0.94). There was no evidence of heterogeneity by severity (p = 0.64) or country income (p = 0.68). The risk of death beyond 24 h of injury was similar in the TXA and placebo groups (432 (11.5%) TXA group vs 421 (11.7%) placebo group; RR 0.98, 95% CI 0.69–1.12). The risk of death at 28 days was 14.0% in the TXA group versus 15.1% in the placebo group (544 vs 568 events; RR 0.93, 95% CI 0.83–1.03). When the CRASH-2 and CRASH-3 trial data were pooled, TXA reduced early death (RR 0.78, 95% CI 0.70–0.87) and death within 28 days (RR 0.88, 95% CI 0.82–0.94). Conclusions: Tranexamic acid reduces early deaths in non-moribund TBI patients regardless of TBI severity or country income. The effect of tranexamic acid in patients with isolated TBI is similar to that in polytrauma. Treatment is safe and even severely injured patients appear to benefit when treated soon after injury. Trial registration: ISRCTN15088122, registered on 19 July 2011; NCT01402882, registered on 26 July 2011