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Introduction: The PROGRESER study is a multicentre, prospective, observational, 3-year follow-up study of a cohort of patients with stage 3 chronic kidney disease (CKD) from different nephrology departments of hospitals in the Spanish healthcare system. The primary study objective was to analyse risk factors for CKD progression, identifying possible differences between patients with and without diabetes mellitus (DM). The secondary objective was to analyse if the cardiovascular risk factors were also associated with CKD progression. Patients and methods: A total of 462 patients (342 men and 120 women; mean age 66.5 ± 11.5 years) were recruited from 25 participating sites in Spain. Clinical, epidemilogical and analytical data were recorder in an electronic registrer each six months. Biological samples were obtained and frozen for a biobank record at baseline and at 18 and 36 months. Results: The initial mean glomerular filtration rate estimated by MDRD and after that reestimated by CKD-EPI was 43.9 ± 7.9 mL/min/1.73 m2; and 29 ± 6,8 mL/min/1,73 m2 at 3 years. 27.3% of patients had microalbuminuria and 22.5% had macroalbuminuria. Two-thirds of the patients (66.2%) presented renal damage progression according to the study criteria (decrease of more than 15% in eGFR over the baseline value). 38.7% presented a reduction in eGFR ≥ 30%; 20.3% had a reduction in eGFR ≥40%; 10.4% had a reduction ≥50% and 6.9% had a reduction ≥57%. Of the 199 diabetics, 134 (67.3%) suffered renal damage progression. Of the 263 non-diabetics, 172 (65.3%) presented progression (p = 0.456). 27.3% of patients had microalbuminuria and 22.5% proteinuria. The study found that CKD progression to a higher stage was not greater in diabetic compared to non-diabetic patients. Multivariate analysis revealed that the presence of arterial hypertension bordered on significance as a progression factor in non-diabetic patients (p = 0.07), and that, in diabetic patients, lower calcium levels and elevated intact parathyroid hormone levels at baseline were associated with progression. Conclusion: in our study we have not found new factors for progression of renal damage, different from the yet well known traditional factors. DM “per se” was not a differential factor for progression in relation with non DM patients. Progression of renal damage in patients with CKD—3 KDOQI may be interpreted in a multifactorial context. The search for new biomarkers, different from traditional ones, is necessary to establish new therapeutic strategies to prevent the progression of CKD. Resumen: Introdución: PROGRESER es un studio multicéntrio, 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 (CCAA) 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 de riesgo cardiovascular (CV) están asociados con dicha progresión. Material y métodos: Se incluyeron 462 pacientes, (342 hombres y 120 mujeres, con edad media de 66.5 ± 11.5 años), 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 43.9 ± 7.9 mL/min/1.73 m2 en el momento basal y 29,9 ± 6,8 mL/min/1,73 m2 a los tres años 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 reduccion ≥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.

Weight excess during the childhood has been one of the most critical public health problems worldwide in the past few decades. It is considered a significant predictor of adulthood obesity, increased cardiometabolic diseases, and premature mortality. Since the Industrial Revolution, childhood obesity has risen due to sedentary lifestyles and poor eating habits, contributing to the development of obesogenic environments around children in different parts of the world. In this regard, Oceania is positioned as the continent with the highest prevalence globally; however, these results did not consider Australia and New Zealand’s data, probably due to the significant differences in population sizes. America has the second highest percentage of children under five who are overweight. Curiously, Asia’s obesity rates are more significant in higher socioeconomic statuses and urban areas than in children aged 2-4 years. Likewise, Africa displays similar epidemiologic behaviour. Qatar and Kuwait are the countries with the highest obesity prevalence on the continent. Moreover, Europe exhibits a notable South-North gradient, which establishes a higher prevalence of obesity in Mediterranean countries than the Nordic ones. In this regard, various prevention and interventional programs have been developed to combat this silent epidemic, focusing their efforts on nutritional education, improving children’s and parents’ lifestyles, and fighting the influence of the media on their behaviour, and decisions. Therefore, the objective of this review was to describe the epidemiological behaviour of childhood obesity from a continental perspective.

Resumen: Aunque el fósforo es un elemento indispensable para la vida, en la naturaleza no se encuentra en estado nativo sino combinado en forma de fosfatos inorgánicos (PO43−), con niveles plasmáticos estrechamente regulados que se asocian a efectos deletéreos y mortalidad cuando estos se encuentran fuera de la normalidad. El interés creciente sobre el acúmulo de PO43− en la fisiopatología humana se originó en el papel que se le atribuyó en la patogenia del hiperparatiroidismo secundario a la enfermedad renal crónica. En este artículo revisamos los mecanismos por los cuales se justificaba dicho efecto y conmemoramos la importante contribución de un grupo español liderado por el Dr. M. Rodríguez, ahora hace justo 25 años, cuando demostraron por primera vez el efecto directo del PO43− sobre la regulación de la síntesis y secreción de hormona paratiroidea (manteniendo la integridad estructural de las glándulas paratiroides en su nuevo modelo experimental. Además de demostrar la importancia del ácido araquidónico (AA) y la vía de la fosfolipasa A2-AA como mediadora de respuestas en la glándula paratiroidea, estos hallazgos fueron predecesores de la reciente descripción del importante papel del PO43− sobre la actividad del receptor-sensor de calcio y alimentaron asimismo diversas líneas de investigación sobre la importancia de la sobrecarga de PO43−, no solo en la fisiopatología del hiperparatiroidismo secundario sino también en su papel patogénico sistémico. Abstract: Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO43−), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO43− in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism in chronic kidney disease. In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr. M. Rodríguez, just 25 years ago, when they first demonstrated the direct effect of PO43− on the regulation of the synthesis and secretion of parathyroid hormone by maintaining the structural integrity of the parathyroid glands in their original experimental model. In addition to demonstrating the importance of arachidonic acid (AA) and the phospholipase A2-AA pathway as a mediator of parathyroid gland response, these findings were predecessors of the recent description of the important role of PO43− on the activity of the calcium sensor-receptor, and also fueled various lines of research on the importance of PO43− overload not only for the pathophysiology of secondary hyperparathyroidism but also of its systemic pathogenic role.

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO43−), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO43− in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism (SHPT) in chronic kidney disease. In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr. M. Rodríguez, just 25 years ago, when they first demonstrated the direct effect of PO43− on the regulation of the synthesis and secretion of parathyroid hormone by maintaining the structural integrity of the parathyroid glands in their original experimental model. In addition to demonstrating the importance of arachidonic acid (AA) and the phospholipase A2-AA pathway as a mediator of parathyroid gland response, these findings were predecessors of the recent description of the important role of PO43- on the activity of the calcium sensor-receptor, and also fueled various lines of research on the importance of PO43− overload not only for the pathophysiology of SHPT but also in its systemic pathogenic role. Resumen: Aunque el fósforo es un elemento indispensable para la vida, en la naturaleza no se encuentra en estado nativo sino combinado en forma de fosfatos inorgánicos (PO43−), con niveles plasmáticos estrechamente regulados que se asocian a efectos deletéreos y mortalidad cuando estos se encuentran fuera de la normalidad. El interés creciente sobre el acúmulo de PO43- en la fisiopatología humana se originó en el papel que se le atribuyó en la patogenia del hiperparatiroidismo secundario a la enfermedad renal crónica. En este artículo revisamos los mecanismos por los cuales se justificaba dicho efecto y conmemoramos la importante contribución de un grupo español liderado por el Dr. M. Rodríguez, ahora hace justo 25 años, cuando demostraron por primera vez el efecto directo del PO43− sobre la regulación de la síntesis y secreción de hormona paratiroidea, manteniendo la integridad estructural de las glándulas paratiroides en su nuevo modelo experimental. Además de demostrar la importancia del ácido araquidónico (AA) y la vía de fosfolipasa A2-AA como mediadora de respuestas en la glándula paratiroidea, estos hallazgos fueron predecesores de la reciente descripción del importante papel del PO43- sobre la actividad del receptor-sensor de calcio y alimentaron asimismo diversas líneas de investigación sobre la importancia de la sobrecarga de PO43− no sólo en la fisiopatología del HPTS sino también en su papel patogénico sistémico.

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.

Objective. Only a few studies assessing the sleep effects of low doses of melatonin (aMT) have been performed in the past, most of them in adults, and only one in subjects with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to provide evidence of the changes induced by aMT doses as low as 1 mg in the sleep pattern of pediatric patients with ADHD under treatment with methylphenidate (MPH). Methods. Children and adolescents (7–15 years) with ADHD who were receiving extended-release MPH were recruited. A seven-week sleep diary was collected prior to starting a four-week treatment with 1 mg of aMT (30 min before bedtime). Seven-day actigraphic assessments of sleep were performed before and after treatment. Results. Twenty-seven patients (17 males, 62.96%) participated in the study, who had been receiving MPH for 1.57 (1.11) months. A significant increase in sleep duration (TST) was observed after one month of treatment (463 (49) min to 485 (41) min; p < 0.040), with nonsignificant improvements in sleep-onset latency (SOL), nocturnal awakenings, or sleep efficiency. Only minor adverse effects were reported. Conclusion. Low doses of melatonin (1 mg) are able to increase TST in children and adolescents with ADHD receiving treatment with psychostimulants, with an adequate tolerability profile. Further placebo-controlled trials adjusting the time of aMT administration to the individual circadian profile should explore the effects of low doses of this hormone to shorten SOL in this population of patients.

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary renal disease. There is an increased rate of cardiovascular disease (CVD) in ADPKD. In this study, we evaluate the prevalence of cardiovascular risk factors, the achievement rates for treatment goals and cardiovascular events (CVE) in ADPKD and their relations with asymptomatic CVD in CKD from other etiologies (CKDoe) and controls. Methods We evaluated 2445 CKD patients (2010–2012). The information collected was: clinical, anthropometric and analytical parameters, treatments and CVD evaluation (intima-media thickness (IMT), atheromatous plaque presence and ankle-brachial index (ABI)). Laboratory, vital status, CVE and hospitalizations were collected for 4 years. Results ADPKD patients had a worse renal function and worst achievement of blood pressure, higher parathormone levels but lower proteinuria compared to CKDoe. ADPKD patients presented lower IMT values than other groups, however, an intermediate rate of pathologic ABI and atheromatous plaque was present. More than half of the patients received statins, achieving LDL-c levels

Background. Very few studies have analyzed early histologic lesions of diabetic nephropathy (DN) in patients without signs of clinical involvement (microalbuminuria). In this study, we analyzed renal histologic lesions in necropsies of diabetic patients with or without previous signs of DN. Methods. Histological material was analyzed from 21 autopsies of type 2 diabetes mellitus (T2DM) patients (9 with albuminuria and 12 without albuminuria) and 4 controls. Histologic lesions were evaluated according to the Tervaert classification. Results. Kidneys of diabetic patients presented significantly higher scores in most histologic indices analyzed (glomerular basal membrane thickening, mild and severe mesangial expansion, nodular sclerosis, interstitial fibrosis, and tubular atrophy) than in nondiabetic controls (p

Background : Adipose tissue accumulation in specific body compartments has been associated with diabetes, hypertension and dyslipidemia. Perirenal fat (PRF) may lead to have direct lipotoxic effects on renal function and intrarenal hydrostatic pressure. This study was undertaken to explore the association of PRF with cardiovascular risk factors and different stages of chronic kidney disease (CKD). Methods : We studied 103 patients with CKD of different stages (1 to 5). PRF was measured by B-mode renal ultrasonography in the distal third between the cortex and the hepatic border and/or spleen. Results : The PRF thickness was greater in CKD patients with impaired fasting glucose than in those with normal glucose levels (1.10 ± 0.40 cm vs. 0.85 ± 0.39 cm, P < 0.01). Patients in CKD stages 4 and 5 (glomerular filtration rate [GFR] < 30 mL/min/1.73 m2) had the highest PRF thickness. Serum triglyceride levels correlated positively with the PRF thickness; the PRF thickness was greater in patients with triglyceride levels ≥ 150 mg/dL (1.09 ± 0.40 cm vs. 0.86 ± 0.36 cm, P < 0.01). In patients with a GFR < 60 mL/min/1.73 m2, uric acid levels correlated positively with the PRF thickness (P < 0.05). Conclusion : In CKD patients, the PRF thickness correlated significantly with metabolic risk factors that could affect kidney function.

The effect of a third vaccine dose (3D) of homologous mRNA vaccine on blood levels of SARS-CoV-2-receptor binding domain (RBD)-total antibodies was assessed in 40 hemodialysis patients (HD) and 21 kidney transplant recipients (KTR) at a median of 46 days after 3D. Anti-RBD antibodies were detected in 39/40 HD and 19/21 KTR. Overall, 3D boosted anti-RBD antibody levels (median: 58-fold increase). Neutralizing antibodies (NtAb) against the Wuhan-Hu-1, Delta, and Omicron variants were detected in 14, 13, and 11 out of 14 HD patients, and in 5, 5, and 4 out of 8 KTR patients, respectively. The median fold increase in NtAb titers in HD patients was 77, 28, and 5 and 56, 37, and 9 in KTR patients for each respective variant. SARS-CoV-2-S S-IFN-γ-producing CD8+ and CD4+ T-cell responses were detected in the majority of HD (35 and 36/37, respectively) and all KTR (16/16) patients at 3D. Overall, the administration of 3D boosted T-cell levels in both population groups. In conclusion, a homologous mRNA COVID-19 vaccine 3D exerts a booster effect on anti-RBD antibodies, NtAb binding to Wuhan-Hu-1, Delta, and Omicron variants, and SARS-CoV-2-S-IFN-γ-producing T cells in both HD and KTR patients. The magnitude of the effect was more marked in HD than KTR patients.

There is a growing interest in the potential role of adipose tissues in cardiac and renal pathophysiology, and determining the mechanisms by which fat compartments around the heart and kidneys influence cardiovascular disease is of clinical importance in both general and high-risk populations. Epicardial fat and perirenal fat have been associated with adverse outcomes in chronic kidney disease (CKD) patients. Epicardial fat is a rich source of free fatty acids and is capable of secreting inflammatory and pro-atherogenic cytokines that promote atherosclerosis through a local paracrine effect. Recent evidence has demonstrated that perirenal fat has a closer correlation with kidney diseases than other visceral fat deposits in obesity or metabolic disturbances. Moreover, perirenal fat has been reported as an independent risk factor for CKD progression and even associated with cardiorenal dysfunction. Accordingly, these forms of organ-specific fat deposits may act as a connecter between vascular and cardiorenal disease. This review explores the possible links between epicardial and perirenal fat and its significant role as a modulator of cardiorenal dysfunction in CKD patients.

Chronic kidney disease (CKD) is associated with a very high morbimortality, mainly from cardiovascular origin, and CKD is currently considered in the high- or very high risk- cardiovascular risk category. CKD-mineral and bone disorders (CKD-MBDs), including vascular and/or valvular calcifications, are also associated with these poor outcomes. Vascular calcification (VC) is very prevalent (both intimal and medial), even in non-dialysis dependent patients, with a greater severity and more rapid progression. Simple X-ray based-scores such as Adragão's (AS) are useful prognostic tools and AS (even AS based on hand-X-ray only) may be superior to the classic Kauppila's score when evaluating non-dialysis CKD patients. Thus, in this mini-review, we briefly review CKD-MBD-related aspects of VC and its complex pathophysiology including the vast array of contributors and inhibitors. Furthermore, although VC is a surrogate marker and is not yet considered a treatment target, we consider that the presence of VC may be relevant in guiding therapeutic interventions, unless all patients are treated with the mindset of reducing the incidence or progression of VC with the currently available armamentarium. Avoiding phosphate loading, restricting calcium-based phosphate binders and high doses of vitamin D, and avoiding normalizing (within the normal limits for the assay) parathyroid hormone levels seem logical approaches. The availability of new drugs and future studies, including patients in early stages of CKD, may lead to significant improvements not only in patient risk stratification but also in attenuating the accelerated progression of VC in CKD.

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.

The purpose of the study is to analyze the impact of vaccination against SARS-CoV-2 on anxiety and depression scores in patients with different modalities of chronic kidney disease. One hundred and seventeen renal patients (50 hemodialysis patients, 13 peritoneal dialysis patients, 32 kidney transplants, and 22 advanced chronic kidney disease patients at pre-dialysis care) were evaluated for depression, anxiety, health-related quality of life (HRQOL), and perceived fears and resources with standardized (Hospital Anxiety and Depression Scale (HADS)) and self-reported questionnaires. The measure points were before vaccination and 15 days after vaccination. The main finding of the study was that there was a decrease in the global mean of normal scores for anxiety and depression symptoms in chronic kidney disease patients post-vaccination. We did not find statistically significant differences in depression or anxiety scores, nor any HRQOL differences between the treatment groups. The three main fears reported by the participants at baseline were those of adverse effects, not getting the vaccine, and lack of information. These findings highlight the potential interest of assessing psychological variables related to the impact of vaccination against SARS-CoV-2. New studies will be required to assess the impact of comprehensive vaccine coverage and its psychological impact.

Pseudoxanthoma elasticum (PXE) is a rare genetic disorder characterized by calcification of elastic fibres, skin lesions, fundus lesions and systemic vascular complications. PXE affects approximately 1 in 160,000 people, typically appearing as a formation of yellow papules containing abnormally calcified elastic fibres. The renal involvement of PXE has been reported. Several factors are known to promote soft tissue and accelerated arterial calcification in chronic kidney disease, including systemic inflammation, altered calcium and phosphate homeostasis, hypertension and a deficiency of endogenous calcification inhibitors. Given the impact of this disease, nephrologists may seek additional supportive features to improve and avoid the risk of complications. Moreover, PXE per se represents an interesting model to evaluate vascular disease in the early stages of renal disease.