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

Matrix metalloproteinases in diabetic kidney disease

Around the world diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD), which is characterized by mesangial expansion, glomerulosclerosis, tubular atrophy, and interstitial fibrosis. The hallmark of the pathogenesis of DKD is an increased extracellular matrix (ECM) accumulation causing thickening of the glomerular and tubular basement membranes, mesangial expansion, sclerosis, and tubulointerstitial fibrosis. The matrix metalloproteases (MMPs) family are composed of zinc-dependent enzymes involved in the degradation and hydrolysis of ECM components. Several MMPs are expressed in the kidney; nephron compartments, vasculature and connective tissue. Given their important role in DKD, several studies have been performed in patients with DKD proposing that the measurement of their activity in serum or in urine may become in the future markers of early DKD. Studies from diabetic nephropathy experimental models suggest that a balance between MMPs levels and their inhibitors is needed to maintain renal homeostasis. This review focuses in the importance of the MMPs within the kidney and their modifications at the circulation, kidney and urine in patients with DKD. We also cover the most important studies performed in experimental models of diabetes in terms of MMPs levels, renal expression and its down-regulation effec

Matrix metalloproteinases in diabetic kidney disease

Around the world diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD), which is characterized by mesangial expansion, glomerulosclerosis, tubular atrophy, and interstitial fibrosis. The hallmark of the pathogenesis of DKD is an increased extracellular matrix (ECM) accumulation causing thickening of the glomerular and tubular basement membranes, mesangial expansion, sclerosis, and tubulointerstitial fibrosis. The matrix metalloproteases (MMPs) family are composed of zinc-dependent enzymes involved in the degradation and hydrolysis of ECM components. Several MMPs are expressed in the kidney; nephron compartments, vasculature and connective tissue. Given their important role in DKD, several studies have been performed in patients with DKD proposing that the measurement of their activity in serum or in urine may become in the future markers of early DKD. Studies from diabetic nephropathy experimental models suggest that a balance between MMPs levels and their inhibitors is needed to maintain renal homeostasis. This review focuses in the importance of the MMPs within the kidney and their modifications at the circulation, kidney and urine in patients with DKD. We also cover the most important studies performed in experimental models of diabetes in terms of MMPs levels, renal expression and its down-regulation effec

La actividad de la ECA2 circulante elevada se relacionan con una mayor severidad del COVID-19

Trabajo presentado en el 53 Congreso de la Sociedad Española de Nefrología, celebrado en Palma de Mallorca (España), del 11 al 13 de noviembre de 2023INTRODUCCIÓN: la enzima conversora de angiotensina 2 (ECA2) es el receptor de entrada a la célula del SARS-CoV-2. La infección por SARS- CoV-2 escinde la ECA2 de la membrana celular, incrementando la ECA2 soluble. El presente estudio tiene como objetivo evaluar si los niveles séricos de la ECA2 durante la primera atención en urgencias de pacientes COVID-19 se relacionan con el pronóstico. MATERIAL Y MÉTODOS: durante la primera ola de la pandemia y entre los meses de marzo y abril de 2020 se obtuvieron en el Hospital Vall d'Hebron de Barcelona muestras de suero en la primera atención en urgencias de 510 pacientes diagnosticados de COVID-19. Se recogieron de la historia clínica la edad, sexo, comorbilidades previas, variables tanto clínicas como analíticas y la evolución de la enfermedad, clasificando como COVID-19 severo aquellos pacientes que fallecieron, ingresaron en UCI o precisaron ventilación mecánica invasiva. La actividad de ECA2 en suero se midió mediante un ensayo de actividad enzimática. RESULTADOS: los pacientes que desarrollaron COVID-19 severo eran mayores y con un mayor número de comorbilidades (Tabla 1). La actividad circulante de ECA2 al ingreso estaba incrementada en 0.24 Unidades Relativas de Fluorescencia(URF)/ng/¿L (IC95%:0.08¿0.41, p<0.001) en pacientes que posteriormente desarrollaban COVID-19 severo. En el modelo de regresión lineal multivariable ajustado por edad, sexo, diabetes, hipertensión, obesidad, enfermedad CV y enfermedad renal, la actividad circulante de ECA2 se seguían asociando a una peor evolución del COVID-19 (p=0.002). La actividad de la ECA2 circulante elevada ¿0.59URF/ng/¿L ofrecían la mejor relación sensibilidad (53%) y especificidad (58%), mientras que valores ¿1.40URF/ng/¿L tenían una especificidad del 95% en la predicción de un COVID-19 severo. CONCLUSIÓN: La actividad de la ECA2 circulante elevada en la primera atención a urgencias de pacientes con infección por COVID-19 se relacionan con un peor pronóstico de la enfermedad