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

Efecto del peróxido de hidrógeno en la producción mitocondr de radicales libres en relación con el envejecimiento = Effect of hydrogen peroxide on mitochondrial free radical production in relation to ageing

Objetivos: el objetivo del presente estudio fue determinar si las mitocondrias dañadas oxidativamente, con un control respiratorio disminuido, producen más radicales libres que en condiciones normales. Esto es importante en relación con propuestas actuales sobre la teoría mitocondrial de envejecimiento por radicales libres. Material y método: las mitocondrias fueron expuestas in vitro a un generador artificial de radicales libres. Se valoró el consumo de oxígeno mitocondrial en reposo (estado 4, sin ADP) y en estado activo (estado 3, con ADP). A partir de estos dos parámetros se obtuvo el valor del control respiratorio, que nos indica el grado de funcionalidad de las mitocondrias. Paralelamente, se midió la producción de H2O2 en la misma suspensión mitocondrial. Resultados: el complejo I se vio más afectado por el daño inducido por radicales libres que los complejos II/III. Sin embargo, no se detectaron cambios estadísticamente significativos en la producción de especies reactivas del oxígeno en ninguno de los complejos respiratorios estudiados. Conclusiones: los presentes resultados sugieren que las mitocondrias dañadas oxidativamente no tienen por qué producir necesariamente más radicales libres. Por tanto, la teoría del círculo vicioso de producción de radicales libres en relación con envejecimiento no es necesariamente cierta. = Objectives: to ascertain whether oxidatively damaged mitochondria, showing a decreased respiratory control index, produce more free radicals than non-stressed mitochondria. This is relevant in relation to present models of the mitochondrial free radical theory of ageing. Material and method: mitochondria were exposed in vitro to an artificial free radical generator. Oxygen consumption at rest (state 4, without adenosine 5'-diphosphate [ADP]) and under active phosphorylation (state 3, with ADP) was measured and the respiratory control ratio was calculated indicating the degree of functionality of the mitochondria. In the same mitochondria H2O2 production was measured in parallel. Results: complex I was more affected than complex II/III by free radical-induced damage. However, mitochondrial production of reactive oxygen species remained unchanged in all the respiratory complexes. Conclusions: the present results suggest that oxidatively damaged mitochondria do not necessarily increase their rate of free radical generation. Thus, the vicious circle theory of mitochondrial free radical generation in relation to ageing is not necessarily true