1. Investigación

Chronic kidney disease (CKD) has been increasing over the last years, with a rate between 0.49% to 0.87% new cases per year. Currently, the number of affected people is around 850 million worldwide. CKD is a slowly progressive disease that leads to irreversible loss of kidney function, end-stage kidney disease, and premature death. Therefore, CKD is considered a global health problem, and this sets the alarm for necessary efficient prediction, management, and disease prevention. At present, modern computer analysis, such as in silico medicine (ISM), denotes an emergent data science that offers interesting promise in the nephrology field. ISM offers reliable computer predictions to suggest optimal treatments in a case-specific manner. In addition, ISM offers the potential to gain a better understanding of the kidney physiology and/or pathophysiology of many complex diseases, together with a multiscale disease modeling. Similarly, -omics platforms (including genomics, transcriptomics, metabolomics, and proteomics), can generate biological data to obtain information on gene expression and regulation, protein turnover, and biological pathway connections in renal diseases. In this sense, the novel patient-centered approach in CKD research is built upon the combination of ISM analysis of human data, the use of in vitro models, and in vivo validation. Thus, one of the main objectives of CKD research is to manage the disease by the identification of new disease drivers, which could be prevented and monitored. This review explores the wide-ranging application of computational medicine and the application of -omics strategies in evaluating and managing kidney diseases.

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.

Periodontitis is a chronic inflammatory disease of the periodontium, or the supportive tissues around the tooth. This disease has been related to different risk factors, such as the presence of plaque and calculus, tobacco smoking, low socioeconomic status, and the immune state of the host. Importantly, the chronic inflammatory environment generated by periodontitis may lead to tooth loss and diverse systemic complications, such as cardiovascular disease, osteoarthritis and metabolic disease. Recent investigations have supported the role of obesity as a risk factor for periodontitis. Furthermore, studies have found obesity to compromise healing after periodontal therapy; however, the mechanisms underlying this association are not well understood. Proteins called 'adipokines' could be the factor linking obesity to periodontitis. Adipokines are bioactive molecules with hormonal properties and a structure similar to cytokines produced by the adipose tissue. Although adipokines have both pro- and anti-inflammatory effects, the shift towards pro-inflammatory actions occurs when the adipose tissue becomes pathological, as observe in the progression of conditions such as obesity or adiposopathy. This article reviews the role of adipokines in the pathophysiology and progression of periodontitis by focusing on their impact on inflammation and the molecular mechanisms through which adipokines contribute to the onset and development of periodontitis.

Bone strength is determined not only by bone quantity [bone mineral density (BMD)] but also by bone quality, including matrix composition, collagen fiber arrangement, microarchitecture, geometry, mineralization, and bone turnover, among others. These aspects influence elasticity, the load-bearing and repair capacity of bone, and microcrack propagation and are thus key to fractures and their avoidance. In chronic kidney disease (CKD)-associated osteoporosis, factors traditionally associated with a lower bone mass (advanced age or hypogonadism) often coexist with non-traditional factors specific to CKD (uremic toxins or renal osteodystrophy, among others), which will have an impact on bone quality. The gold standard for measuring BMD is dual-energy X-ray absorptiometry, which is widely accepted in the general population and is also capable of predicting fracture risk in CKD. Nevertheless, a significant number of fractures occur in the absence of densitometric World Health Organization (WHO) criteria for osteoporosis, suggesting that methods that also evaluate bone quality need to be considered in order to achieve a comprehensive assessment of fracture risk. The techniques for measuring bone quality are limited by their high cost or invasive nature, which has prevented their implementation in clinical practice. A bone biopsy, high-resolution peripheral quantitative computed tomography, and impact microindentation are some of the methods established to assess bone quality. Herein, we review the current evidence in the literature with the aim of exploring the factors that affect both bone quality and bone quantity in CKD and describing available techniques to assess them.

The novel disease produced by SARS-CoV-2 mainly harms the respiratory tract, but it has shown the capacity to affect multiple organs. Epidemiologic evidence supports the relationship between Coronavirus Disease 2019 (COVID-19) and pancreatic and hepatic injury development, identified by alterations in these organ function markers. In this regard, it is important to ascertain how the current prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) might affect COVID-19 evolution and complications. Although it is not clear how SARS-CoV-2 affects both the pancreas and the liver, a multiplicity of potential pathophysiological mechanisms seem to be implicated; among them, a direct viral-induced injury to the organ involving liver and pancreas ACE2 expression. Additionally, immune system dysregulation, coagulopathies, and drugs used to treat the disease could be key for developing complications associated with the patient’s clinical decline. This review aims to provide an overview of the available epidemiologic evidence regarding developing liver and pancreatic alterations in patients with COVID-19, as well as the possible role that NAFLD/NASH might play in the pathophysiological mechanisms underlying some of the complications associated with COVID-19. This review employed a comprehensive search on PubMed using relevant keywords and filters. From the initial 126 articles, those aligning with the research target were selected and evaluated for their methodologies, findings, and conclusions. It sheds light on the potential pathophysiological mechanisms underlying this relationship. As a result, it emphasises the importance of monitoring pancreatic and hepatic function in individuals affected by COVID-19.

Aim: Sodium-glucose co-transporter 2 inhibitors and mineralocorticoid receptor antagonists reduce albuminuria and the risk of kidney failure. The aim of this study was to investigate the effects of both agents alone and in combination on markers of the glomerular endothelial glycocalyx and tubular function. Methods: This post-hoc analysis utilized data of the ROTATE-3 study, a randomized cross-over study in 46 adults with chronic kidney disease and urinary albumin excretion ≥100 mg/24 h, who were treated for 4 weeks with dapagliflozin, eplerenone or its combination. The effects of dapagliflozin, eplerenone and the combination on outcome measures such as heparan sulphate, neuro-hormonal markers and tubular sodium handling were assessed with mixed repeated measures models. Results: The mean percentage change from baseline in heparan sulphate after 4 weeks treatment with dapagliflozin, eplerenone or dapagliflozin-eplerenone was -34.8% (95% CI -52.2, -10.9), -5.9% (95% CI -32.5, 31.3) and -28.1% (95% CI -48.4, 0.1) respectively. The mean percentage change from baseline in plasma aldosterone was larger with eplerenone [38.9% (95% CI 2.8, 87.7)] and dapagliflozin-eplerenone [32.2% (95% CI -1.5, 77.4)], compared with dapagliflozin [-12.5% (95% CI -35.0, 17.8)], respectively. Mean percentage change from baseline in copeptin with dapagliflozin, eplerenone or dapagliflozin-eplerenone was 28.4% (95% CI 10.7, 49.0), 4.2% (95% CI -10.6, 21.4) and 23.8% (95% CI 6.6, 43.9) respectively. Dapagliflozin decreased proximal absolute sodium reabsorption rate by 455.9 mmol/min (95% CI -879.2, -32.6), while eplerenone decreased distal absolute sodium reabsorption rate by 523.1 mmol/min (95% CI -926.1, -120.0). Dapagliflozin-eplerenone decreased proximal absolute sodium reabsorption [-971.0 mmol/min (95% CI -1411.0, -531.0)], but did not affect distal absolute sodium reabsorption [-9.2 mmol/min (95% CI -402.0, 383.6)]. Conclusions: Dapagliflozin and eplerenone exert different effects on markers of glomerular and tubular function supporting the hypothesis that different mechanistic pathways may account for their kidney protective effects.

Cancer is a process involving cell mutation, increased proliferation, invasion, and metastasis. Over the years, this condition has represented one of the most concerning health problems worldwide due to its significant morbidity and mortality. At present, the incidence of cancer continues to grow exponentially. Thus, it is imperative to open new avenues in cancer research to understand the molecular changes driving DNA transformation, cell-to-cell interaction derangements, and immune system surveillance decay. In this regard, evidence supports the relationship between chronic inflammation and cancer. In light of this, a group of bioactive lipids derived from polyunsaturated fatty acids (PUFAs) may have a position as novel anti-inflammatory molecules known as the specialized pro-resolving mediators (SPMs), a group of pro-resolutive inflammation agents that could improve the anti-tumor immunity. These molecules have the potential role of chemopreventive and therapeutic agents for various cancer types, and their effects have been documented in the scientific literature. Thus, this review objective centers around understanding the effect of SPMs on carcinogenesis and their potential therapeutic effect.

Longevity has been a topic of interest since the beginnings of humanity, yet its aetiology and precise mechanisms remain to be elucidated. Aging is currently viewed as a physiological phenomenon characterized by the gradual degeneration of organic physiology and morphology due to the passage of time where both external and internal stimuli intervene. The influence of intrinsic factors, such as progressive telomere shortening, genome instability due to mutation buildup, the direct or indirect actions of age-related genes, and marked changes in epigenetic, metabolic, and mitochondrial patterns constitute a big part of its underlying endogenous mechanisms. On the other hand, several psychosocial and demographic factors, such as diet, physical activity, smoking, and drinking habits, may have an even more significant impact on shaping the aging process. Consequentially, implementing dietary and exercise patterns has been proposed as the most viable alternative strategy for attenuating the most typical degenerative aging changes, thus increasing the likelihood of prolonging lifespan and achieving successful aging.

Background: Chronic kidney disease (CKD) is a common complication of a non-kidney solid organ transplant (NKSOT). Identifying predisposing factors is crucial for an early approach and correct referral to nephrology. Methods: This is a single-center retrospective observational study of a cohort of CKD patients under follow-up in the Nephrology Department between 2010 to 2020. Statistical analysis was performed between all the risk factors and four dependent variables: end-stage renal disease (ESKD); increased serum creatinine ≥50%; renal replacement therapy (RRT); and death in the pre-transplant, peri-transplant, and post-transplant periods. Results: 74 patients were studied (7 heart transplants, 34 liver transplants, and 33 lung transplants). Patients who were not followed-up by a nephrologist in the pre-transplant (p < 0.027) or peri-transplant (p < 0.046) periods and those who had the longest time until an outpatient clinic follow-up (HR 1.032) were associated with a higher risk of creatinine increase ≥50%. Receiving a lung transplant conferred a higher risk than a liver or heart transplant for developing a creatinine increase ≥50% and ESKD. Peri-transplant mechanical ventilation, peri-transplant and post-transplant anticalcineurin overdose, nephrotoxicity, and the number of hospital admissions were significantly associated with a creatinine increase ≥50% and developing ESKD. Conclusions: Early and close follow-up by a nephrologist was associated with a decrease in the worsening of renal function.