1. Investigación

Introducción: PROGRESER es un estudio multicéntrico, prospectivo, observacional, con tres años de seguimiento, de una cohorte de pacientes con enfermedad renal crónica (ERC)-3 KDOQI, incluidos en servicios de Nefrología del Sistema Nacional de Salud en 14 comunidades autónomas de España. El objetivo primario fue analizar los factores de riesgo asociados con la progresión de la ERC, para identificar posibles diferencias entre pacientes con y sin diabetes mellitus (DM). El objetivo secundario fue investigar si los factores asociados con hospitalizaciones y mortalidad. Material y métodos: Se incluyeron 462 pacientes (342 hombres y 120 mujeres, con una edad media de 66,5 ± 11,5 añ os), reclutados en 25 centros. Se recogieron datos epidemiológicos, clínicos y analíticos cada seis meses, registrados en cuaderno electrónico. Se recogieron y congelaron muestras biológicas para biobanco basales y a 18 y 36 meses.Resultados: El filtrado glomerular estimado (FGe), calculado inicialmente mediante la ecuación Modification of Diet in Renal Disease (MDRD) y después recalculado mediante CKD-EPI fue de 43,9 ± 7,9 mL/min/1,73 m2 en el momento basal y de 29,9 ± 6,8 mL/min/1,73 m2 a los tres añ os de seguimiento. Dos tercios de los pacientes (66,2%) presentaron progresión del daño renal según criterio del estudio (descenso mayor del 15% del FGe sobre el valor basal). Un 38,7% presentaron una reducción del FGe ≥ 30%; un 20,3% tuvieron una reducción del FGe≥ 40%; un 10,4% tuvieron una reducción ≥ 50% y un 6,9%, una reducción ≥ 57%. De los 199 diabéticos, 134 (67,3%) presentaron progresión. De los 263 no diabéticos, 172 (65,3%) presentaron progresión (p = 0,456). El 27,3% de pacientes presentaban microalbuminuria y el 22,5%, proteinuria. El estudio mostró que la progresión de un estadio a otros más avanzados no fue superior en los pacientes con DM respecto a los no diabéticos. El análisis multivariante reveló que la presencia de hipertensión arterial (HTA) se aproximó a la significación estadística (p = 0,07) asociado a la progresión en los pacientes sin DM, y que en los pacientes con DM unos niveles basales de calcio más bajos y de PTH-i más elevados sobre el valor basal tuvieron significación estadística como factores de progresión de la ERC. Conclusión: Nuestro estudio no ha revelado nuevos factores de progresión de daño renal con relación a los factores clásicos ya conocidos. No hemos encontrado diferencias significativas en cuanto a la progresión en pacientes con y sin DM. La progresión del daño renal en pacientes con ERC-3 KDOQI debe interpretarse en un contexto multifactorial. Se precisa la búsqueda de nuevos biomarcadores, diferentes de los tradicionales, para establecer nuevas estrategias terapéuticas para prevenir la progresión de la ERC.

Atherosclerosis is one of the most relevant and prevalent cardiovascular diseases of our time. It is one of the pathological entities that increases the morbidity and mortality index in the adult population. Pathophysiological connections have been observed between atherosclerosis and the gut microbiome (GM), represented by a group of microorganisms that are present in the gut. These microorganisms are vital for metabolic homeostasis in humans. Recently, direct and indirect mechanisms through which GM can affect the development of atherosclerosis have been studied. This has led to research into the possible modulation of GM and metabolites as a new target in the prevention and treatment of atherosclerosis. The goal of this review is to analyze the physiopathological mechanisms linking GM and atherosclerosis that have been described so far. We also aim to summarize the recent studies that propose GM as a potential target in atherosclerosis management.

Diabetic kidney disease (DKD) is the leading cause of chronic and end-stage kidney disease worldwide. Its pathogenic mechanism is complex, and it can affect the entire structures of the kidneys such as the glomerulus, tubules and interstitium. Currently, the urinary albumin excretion rate and the estimated glomerular filtration rate are widely accepted as diagnostic criteria. However, some studies have reported a different or non-classical clinical course of DKD, with some patients showing declined kidney function with normal levels of albuminuria, known as the 'non-albuminuric DKD' phenotype. The pathogenesis of this phenotype remains unclear, but some clinical and pathological features have been postulated. This review explores the evidence regarding this topic.

Introduction: Although small-sample size studies have shown that basal alterations of estimated glomerular filtration rate (eGFR) are related to short- and mid-term higher mortality in acute heart failure (AHF), there is scarce information on the influence of an altered eGFR on long-term mortality and readmissions. Therefore, this multicenter study sought to investigate the relationship between eGFR on admission for AHF and both long-term mortality and readmissions in a large sample of patients. Methods: We retrospectively evaluated 4,595 patients consecutively discharged after admission for AHF at three tertiary-care hospitals from January 1, 2008, to January 1, 2020. To investigate the effect of eGFR on admission with long-term morbimortality, we stratified the patients according to four eGFR categories: <30 mL·min−1·1.73 m−2 (G4 and G5 patients, n = 534), 30–44 mL·min−1·1.73 m−2 (G3b patients, n = 882), 45–59 mL·min−1·1.73 m−2 (G3a patients, n = 1,080), and ≥60 mL·min−1·1.73 m−2 (G1 and G2 patients, n = 2,099). eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation within the first 24 h following admission. Results: At a median follow-up of 2.20 years, multivariate analyses revealed that compared to G1 and G2 patients, G4 and G5 patients exhibited a higher risk of all-cause (HR = 1.15, 95% CI: 01.02–1.30, p = 0.020) and cardiovascular (CV) (HR = 1.20, 95% CI: 1.04–1.39, p = 0.013) mortality. Similarly, multivariate analyses also showed that the lower the eGFR, the higher the risk of readmissions. In fact, compared to G1 and G2 patients, G4 and G5 patients displayed significantly increased incident rate ratios of total all-cause (28%), CV (26%), and HF-related (30%) readmissions. Conclusion: Data from this large study provide evidence that an eGFR below 30 mL·min−1·1.73 m−2 on admission could be an independent predictor for long-term mortality and readmissions in patients with AHF.

Type 2 diabetes mellitus (T2DM) affects an estimated 463 million people worldwide, equivalent to 1 in 11 adults. Moreover, the rapid growth of this disease has resulted in a high incidence of diabetic kidney disease (DKD), which, together with hypertension, is the main cause of chronic kidney disease (CKD). Hyperglycaemia, low-grade inflammation, altered lipid metabolism and hyperactivation of the renin–angiotensin–aldosterone system (RAAS) seem to be interrelated mechanisms contributing to both T2DM and microvascular complications. The introduction of drugs such as sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists has improved the ability to slow the progression of DKD, and has also demonstrated benefits in cardiovascular disease. Beyond the effects of these novel antidiabetic drugs, a body of evidence suggests that the overactivation of the mineralocorticoid receptor also contributes to CKD progression. Moreover, new and ongoing trials have demonstrated that the selective nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone improves the risk of CKD progression and cardiovascular events in patients with CKD and T2DM and optimized RAAS blockade. We review the rationale for the development and use of MRA drugs to slow CKD progression in patients with DKD, as well as other pleiotropic effects, and highlight the warnings associated with these agents.

Background. Over the last few years, the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) has increased substantially in medical practice due to their documented benefits in cardiorenal and metabolic health. In this sense, and in addition to being used for glycemic control in diabetic patients, these drugs also have other favorable effects such as weight loss and lowering blood pressure, and more recently, they have been shown to have cardio and renoprotective effects with anti-inflammatory properties. Concerning the latter, the individual or associated use of these antihyperglycemic agents has been linked with a decrease in proinflammatory cytokines and with an improvement in the inflammatory profile in chronic endocrine-metabolic diseases. Hence, these drugs have been positioned as first-line therapy in the management of diabetes and its multiple comorbidities, such as obesity, which has been associated with persistent inflammatory states that induce dysfunction of the adipose tissue. Moreover, other frequent comorbidities in long-standing diabetic patients are chronic complications such as diabetic kidney disease, whose progression can be slowed by SGLT2i and/or GLP-1RA. The neuroendocrine and immunometabolism mechanisms underlying adipose tissue inflammation in individuals with diabetes and cardiometabolic and renal diseases are complex and not fully understood. Summary. This review intends to expose the probable molecular mechanisms and compile evidence of the synergistic or additive anti-inflammatory effects of SGLT2i and GLP-1RA and their potential impact on the management of patients with obesity and cardiorenal compromise.