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Anaemia is a common complication of chronic kidney disease (CKD) and is associated with poor long-term outcomes and quality of life. The use of supplemental iron, erythropoiesis stimulating agents (ESAs) and blood transfusions has been the mainstay of treatment of anaemia in CKD for more than three decades. Despite available treatments, CKD patients with anaemia are undertreated and moderate-to-severe anaemia remains prevalent in the CKD population. Anaemia has consistently been associated with greater mortality, hospitalisation, cardiovascular events, and CKD progression in patients with CKD, and the risk increases with anaemia severity. Hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) inhibitors have a novel mechanism of action by mimicking the body's response to hypoxia and have emerged as an alternative to ESAs for the treatment of anaemia in CKD. Their efficacy in correcting and maintaining haemoglobin has been demonstrated in over 30 phase 3 clinical trials. Additionally, HIF activation results in various pleiotropic effects beyond erythropoiesis with cholesterol reduction and improved iron homeostasis and potential anti-inflammatory effects. The long-term safety of these agents, particularly with respect to cardiovascular and thromboembolic events, and their possible effect on tumor growth requires to be fully elucidated. This document presents in detail the effects of HIF-PH inhibitors, describes their mechanisms of action and pharmacologic properties, and discusses their place in the treatment of anaemia in CKD according to the available evidence.
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Despite current treatments, which include renin angiotensin system blockers and SGLT2 inhibitors, the risk of progression of kidney disease among patients with diabetes and chronic kidney disease (CKD) remains unacceptably high. The pathogenesis of CKD in patients with diabetes is complex and includes hemodynamic and metabolic factors, as well as inflammation and fibrosis. Finerenone is a highly selective nonsteroidal mineralocorticoid antagonist that, in contrast to current therapies, may directly reduce inflammation and fibrosis, thus adding value in the management of these patients. In fact, finerenone decreases albuminuria and slows CKD progression in persons with diabetes. We now review the mechanisms of action of finerenone, the results of recent clinical trials, and the integration of the kidney and cardiovascular protection afforded by finerenone in the routine care of patients with diabetes and CKD.
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Diabetes Mellitus , Nefropatías Diabéticas , Insuficiencia Renal Crónica , Humanos , Nefropatías Diabéticas/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Inflamación , FibrosisRESUMEN
Despite a large number of people globally being affected by rare kidney diseases, research support and health care policy programs usually focus on the management of the broad spectrum of CKD without particular attention to rare causes that would require a targeted approach for proper cure. Hence, specific curative approaches for rare kidney diseases are scarce, and these diseases are not treated optimally, with implications on the patients' health and quality of life, on the cost for the health care system, and society. There is therefore a need for rare kidney diseases and their mechanisms to receive the appropriate scientific, political, and policy attention to develop specific corrective approaches. A wide range of policies are required to address the various challenges that target care for rare kidney diseases, including the need to increase awareness, improve and accelerate diagnosis, support and implement therapeutic advances, and inform the management of the diseases. In this article, we provide specific policy recommendations to address the challenges hindering the provision of targeted care for rare kidney diseases, focusing on awareness and prioritization, diagnosis, management, and therapeutic innovation. In combination, the recommendations provide a holistic approach aiming for all aspects of rare kidney disease care to improve health outcomes, reduce the economic effect, and deliver benefits to society. Greater commitment from all the key stakeholders is now needed, and a central role should be assigned to patients with rare kidney disease to partner in the design and implementation of potential solutions.
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Enfermedades Renales , Calidad de Vida , Humanos , Atención a la Salud , Política de Salud , Enfermedades Renales/diagnóstico , Enfermedades Renales/terapiaAsunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Humanos , Atrasentán/uso terapéutico , Antagonistas de los Receptores de la Endotelina A/uso terapéutico , Nefropatías Diabéticas/tratamiento farmacológico , Albuminuria , Antagonistas de los Receptores de Endotelina/uso terapéutico , Pirrolidinas , Endotelina-1RESUMEN
In a recent issue of ckj, Piedrafita et al. reported that urine tryptophan and kynurenine are reduced in cardiac bypass surgery patients that develop acute kidney injury (AKI), suggesting reduced activity of the kynurenine pathway of nicotinamide (NAM) adenine dinucleotide (NAD+) synthesis from tryptophan. However, NAM supplementation aiming at repleting NAD+ did not replete kidney NAD+ and did not improve glomerular filtration or reduce histological injury in ischaemic-reperfusion kidney injury in mice. The lack of improvement of kidney injury is partially at odds with prior reports that did not study kidney NAD+, glomerular filtration or histology in NAM-treated wild-type mice with AKI. We now present an overview of research on therapy with vitamin B3 vitamers and derivate molecules {niacin, Nicotinamide [NAM; niacinamide], NAM riboside [Nicotinamide riboside (NR)], Reduced nicotinamide riboside [NRH] and NAM mononucleotide} in kidney injury, including an overview of ongoing clinical trials, and discuss the potential explanations for diverging reports on the impact of these therapeutic approaches on pre-clinical acute and chronic kidney disease.
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Phosphate is a key uremic toxin associated with adverse outcomes. As chronic kidney disease (CKD) progresses, the kidney capacity to excrete excess dietary phosphate decreases, triggering compensatory endocrine responses that drive CKD-mineral and bone disorder (CKD-MBD). Eventually, hyperphosphatemia develops, and low phosphate diet and phosphate binders are prescribed. Recent data have identified a potential role of the gut microbiota in mineral bone disorders. Thus, parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched in the Th17 cell-inducing taxa segmented filamentous bacteria. Furthermore, the microbiota was required for PTH to stimulate bone formation and increase bone mass, and this was dependent on bacterial production of the short-chain fatty acid butyrate. We review current knowledge on the relationship between phosphate, microbiota and CKD-MBD. Topics include microbial bioactive compounds of special interest in CKD, the impact of dietary phosphate and phosphate binders on the gut microbiota, the modulation of CKD-MBD by the microbiota and the potential therapeutic use of microbiota to treat CKD-MBD through the clinical translation of concepts from other fields of science such as the optimization of phosphorus utilization and the use of phosphate-accumulating organisms.
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Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/metabolismo , Microbioma Gastrointestinal/inmunología , Hiperfosfatemia/metabolismo , Fósforo Dietético/metabolismo , Insuficiencia Renal Crónica/complicaciones , Animales , Quelantes/administración & dosificación , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/inmunología , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/microbiología , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/terapia , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Salud Holística , Humanos , Hiperfosfatemia/inmunología , Hiperfosfatemia/microbiología , Hiperfosfatemia/terapia , Ratones , Hormona Paratiroidea/sangre , Hormona Paratiroidea/metabolismo , Fósforo Dietético/efectos adversos , Fósforo Dietético/antagonistas & inhibidores , Fósforo Dietético/sangre , Probióticos/uso terapéutico , Insuficiencia Renal Crónica/inmunología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/terapia , Células Th17/inmunologíaRESUMEN
Pseudomonas aeruginosa is a primary bacterial model to study cooperative behaviors because it yields exoproducts such as siderophores and exoproteases that act as public goods and can be exploited by selfish nonproducers behaving as social cheaters. Iron-limited growth medium, mainly casamino acids medium supplemented with transferrin, is typically used to isolate and study nonproducer mutants of the siderophore pyoverdine. However, using a protein as the iron chelator could inadvertently select mutants unable to produce exoproteases, since these enzymes can degrade the transferrin to facilitate iron release. Here we investigated the evolutionary dynamics of pyoverdine and exoprotease production in media in which iron was limited by using either transferrin or a cation chelating resin. We show that concomitant loss of pyoverdine and exoprotease production readily develops in media containing transferrin, whereas only pyoverdine loss emerges in medium treated with the resin. Characterization of exoprotease- and pyoverdine-less mutants revealed loss in motility, different mutations, and large genome deletions (13-33 kb) including Quorum Sensing (lasR, rsal, and lasI) and flagellar genes. Our work shows that using transferrin as an iron chelator imposes simultaneous selective pressure for the loss of pyoverdine and exoprotease production. The unintended effect of transferrin uncovered by our experiments can help to inform the design of similar studies.
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Hierro , Pseudomonas aeruginosa , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Exopeptidasas , Hierro/metabolismo , Oligopéptidos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Sideróforos , TransferrinaRESUMEN
Klotho has antiaging properties, and serum levels decrease with physiological aging and aging-related diseases, such as hypertension, cardiovascular, and chronic kidney disease. Klotho deficiency in mice results in accelerated aging and cardiovascular injury, whereas Klotho supplementation slows down the progression of aging-related diseases. The pleiotropic functions of Klotho include, but are not limited to, inhibition of insulin/IGF-1 (insulin-like growth factor 1) and WNT (wingless-related integration site) signaling pathways, suppression of oxidative stress and aldosterone secretion, regulation of calcium-phosphate homeostasis, and modulation of autophagy with inhibition of apoptosis, fibrosis, and cell senescence. Accumulating evidence shows an interconnection between Klotho deficiency and hypertension, and Klotho gene polymorphisms are associated with hypertension in humans. In this review, we critically review the current understanding of the role of Klotho in the development of essential hypertension and the most important underlying pathways involved, such as the FGF23 (fibroblast growth factor 23)/Klotho axis, aldosterone, Wnt5a/RhoA, and SIRT1 (Sirtuin1). Based on this critical review, we suggest avenues for further research.
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Envejecimiento , Hipertensión Esencial/genética , Glucuronidasa/genética , Polimorfismo de Nucleótido Simple , Animales , Hipertensión Esencial/metabolismo , Hipertensión Esencial/fisiopatología , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Glucuronidasa/metabolismo , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Proteínas Klotho , Ratones Noqueados , Vía de Señalización Wnt/genéticaRESUMEN
OBJECTIVE: Drinking coffee is one of the most common daily habits, especially in the developed world. Along with caffeine, coffee has various ingredients that have been suggested to have beneficial effects, including antioxidant, antiinflammatory, anticarcinogenic, antithrombotic and antifibrotic effects. In this systematic review and meta-analysis, we investigated the relationship between coffee intake and chronic kidney disease (CKD) related outcomes. DESIGN AND METHODS: Literature search was performed through PubMed/Medline, Web of Science, Embase (Elsevier), and the Cochrane Central Register of Controlled Trials (Wiley) from 1960 to February 2020. Incidence of CKD, the progression of CKD, and CKD-associated mortality have been evaluated in relation to coffee consumption and the amount of consumption. The Newcastle-Ottawa scale was used for quality assessment of included studies. RESULTS: 12 studies were included in the analysis (7 prospective, 5 cross-sectional) involving 505,841 subjects. 7 studies investigated the relationship between coffee consumption and incident CKD and showed that coffee consumption was associated with a significant decrease in the risk for incident CKD outcome (RR 0.86, 95% CI 0.76 to 0.97, P = .01) with a greater decrease in individuals taking ≥2 cups/day compared to those who drank ≤1 cup/day. There was a significantly lower risk of incident end stage kidney disease (ESKD) in coffee users (HR 0.82, 95% CI 0.72 to 0.94, P = .005). Coffee consumption was also associated with a lower risk of albuminuria (OR 0.81, 95% CI 0.68 to 0.97, P = .02). Overall, the risk of death related to CKD was lower in coffee users (HR 0.72, 95% CI 0.54 to 0.96, P = .02). CONCLUSION: Coffee intake was dose-dependently associated with lower incident CKD, ESKD, and albuminuria.
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Café , Riñón/efectos de los fármacos , Insuficiencia Renal Crónica/prevención & control , HumanosRESUMEN
The lack of effective pharmacological treatments for acute kidney injury (AKI) remains a significant public health problem. Given the involvement of apoptosis and regulated necrosis in the initiation and progression of AKI, the inhibition of cell death may contribute to AKI prevention/recovery. Curcuminoids are a family of plant polyphenols that exhibit attractive biological properties that make them potentially suitable for AKI treatment. Now, in cultured tubular cells, we demonstrated that a crosslinked self-assembled star-shaped polyglutamate (PGA) conjugate of bisdemethoxycurcumin (St-PGA-CL-BDMC) inhibits apoptosis and necroptosis induced by Tweak/TNFα/IFNγ alone or concomitant to caspase inhibition. St-PGA-CL-BDMC also reduced NF-κB activation and subsequent gene transcription. In vivo, St-PGA-CL-BDMC prevented renal cell loss and preserved renal function in mice with folic acid-induced AKI. Mechanistically, St-PGA-CL-BDMC inhibited AKI-induced apoptosis and expression of ferroptosis markers and also decreased the kidney expression of genes involved in tubular damage and inflammation, while preserving the kidney expression of the protective factor, Klotho. Thus, due to renal accumulation and attractive pharmacological properties, the application of PGA-based therapeutics may improve nephroprotective properties of current AKI treatments.
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Lesión Renal Aguda/tratamiento farmacológico , Diarilheptanoides/farmacología , Túbulos Renales/efectos de los fármacos , Ácido Poliglutámico/farmacología , Sustancias Protectoras/farmacología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/inmunología , Lesión Renal Aguda/patología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Línea Celular , Diarilheptanoides/química , Diarilheptanoides/uso terapéutico , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Ácido Fólico/toxicidad , Glucuronidasa/metabolismo , Humanos , Túbulos Renales/patología , Proteínas Klotho , Ratones , Conformación Molecular , FN-kappa B/metabolismo , Necrosis/tratamiento farmacológico , Necrosis/inmunología , Necrosis/patología , Ácido Poliglutámico/química , Ácido Poliglutámico/uso terapéutico , Sustancias Protectoras/química , Sustancias Protectoras/uso terapéutico , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Relación Estructura-Actividad , Transcripción Genética/efectos de los fármacosRESUMEN
Fibroblast growth factor 23 (FGF23) increases phosphorus excretion and decreases calcitriol (1,25(OH)2D) levels. FGF23 increases from early stages of renal failure. We evaluated whether strict control of phosphorus intake in renal failure prevents the increase in FGF23 and to what extent inflammation impairs regulation of FGF23. The study was performed in 5/6 nephrectomized (Nx) Wistar rats fed diets containing 0.2-1.2% phosphorus for 3 or 15 days. FGF23 levels significantly increased in all Nx groups in the short-term (3-day) experiment. However, at 15 days, FGF23 increased in all Nx rats except in those fed 0.2% phosphorus. In a second experiment, Nx rats fed low phosphorus diets (0.2 and 0.4%) for 15 days received daily intraperitoneal lipopolysaccharide (LPS) injections to induce inflammation. In these rats, FGF23 increased despite the low phosphorus diets. Thus, higher FGF23 levels were needed to maintain phosphaturia and normal serum phosphorus values. Renal Klotho expression was preserved in Nx rats on a 0.2% phosphorus diet, reduced on a 0.4% phosphorus diet, and markedly reduced in Nx rats receiving LPS. In ex vivo experiments, high phosphorus and LPS increased nuclear ß-catenin and p65-NFκB and decreased Klotho. Inhibition of inflammation and Wnt signaling activation resulted in decreased FGF23 levels and increased renal Klotho. In conclusion, strict control of phosphorus intake prevented the increase in FGF23 in renal failure, whereas inflammation independently increased FGF23 values. Decreased Klotho may explain the renal resistance to FGF23 in inflammation. These effects are likely mediated by the activation of NFkB and Wnt/ß-catenin signaling.
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Factores de Crecimiento de Fibroblastos/metabolismo , Inflamación/metabolismo , Riñón/metabolismo , Uremia/metabolismo , Animales , Calcitriol/farmacología , Calcio/metabolismo , Factor-23 de Crecimiento de Fibroblastos , Riñón/efectos de los fármacos , Masculino , Fósforo/metabolismo , Ratas Wistar , Insuficiencia Renal/metabolismo , Insuficiencia Renal Crónica/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , Vía de Señalización Wnt/fisiologíaRESUMEN
Six years ago, a comprehensive review by the EURECA-m working group of the ERA-EDTA thoroughly addressed the drivers of mortality in patients with end-stage kidney disease. Not unexpectedly, the key global driver of early death in these patients was the lack of access to kidney replacement therapy. However, and contrary to the expectations of non-nephrologists, mortality was still high when kidney replacement therapy was provided. This was due to excess cardiovascular and non-cardiovascular mortality, and the need to further characterize correctable risk factors and eventually test the impact of correcting them was emphasized. In this issue of ckj, seven reports address risk factors for death in non-dialysis chronic kidney disease (CKD), dialysis and kidney transplant patients. They characterize irreversible (e.g. sex; age; genetic variants of the KL gene encoding the anti-ageing protein Klotho) and reversible (obesity; mineral and bone disorder parameters; anti-depressant drugs, especially those that increase the QT; amputation; public health investments) factors associated with mortality of CKD patients on or off kidney replacement therapy.
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BACKGROUND: Epidemiological studies have suggested a survival benefit for hemodialysis patients on paricalcitol or calcitriol, but nutritional vitamin D supplementation of patients already on vitamin D receptor (VDR) activators is controversial. METHODS: This observational retrospective cohort study was conducted with prospectively collected data from all consecutive patients with chronic kidney disease (CKD) who underwent hemodialysis under routine clinical practice conditions for two years. RESULTS: Of the 129 patients, 89 were treated with calcidiol, paricalcitol, and/or calcitriol. The patients with any vitamin D formulation had higher serum concentrations of 25-hydroxy vitamin D and fibroblast growth factor-23 and tended to have higher mortality rates (42% vs. 25%, p = 0.07). On subgroup analysis, any calcidiol treatment or calcidiol combined with paricalcitol associated with significantly higher mortality rates than no treatment (47% and 62.5%, p = 0.043 and 0.008, respectively). The association between calcidiol/paricalcitol treatment and elevated mortality remained significant after adjusting for age, sex, diabetes, C-reactive protein, and hemodialysis vintage. Any calcidiol and calcidiol/paricalcitol treatment exhibited a dose-response relationship with mortality (p for trend: 0.002 and 0.005, respectively). CONCLUSIONS: These data draw attention to the hitherto unexplored safety of calcidiol supplementation in patients on hemodialysis, especially in those already on vitamin D. Until clinical trials demonstrate the safety and efficacy of this approach, caution should be exercised when prescribing these patients ≥0.5 calcidiol mg/month.
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Calcifediol/efectos adversos , Calcifediol/uso terapéutico , Diálisis Renal , Anciano , Calcifediol/administración & dosificación , Ergocalciferoles/administración & dosificación , Ergocalciferoles/efectos adversos , Ergocalciferoles/uso terapéutico , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Humanos , Masculino , Persona de Mediana Edad , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D , Vitaminas/administración & dosificación , Vitaminas/efectos adversos , Vitaminas/farmacologíaRESUMEN
Along with amazing technological advances, the industrial revolution of the mid-19th century introduced new sources of pollution. By the mid-20th century, the effects of these changes were beginning to be felt around the world. Among these changes, health problems due to environmental air pollution are increasingly recognized. At the beginning, respiratory and cardiovascular diseases were emphasized. However, accumulated data indicate that every organ system in the body may be involved, and the kidney is no exception. Although research on air pollution and kidney damage is recent, there is now scientific evidence that air pollution harms the kidney. In this holistic review, we have summarized the epidemiology, disease states and mechanisms of air pollution and kidney damage.
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Chronic kidney disease (CKD) in patients with diabetes mellitus (DM) is a major problem of public health. Currently, many of these patients experience progression of cardiovascular and renal disease, even when receiving optimal treatment. In previous years, several new drug classes for the treatment of type 2 DM have emerged, including inhibitors of renal sodium-glucose co-transporter-2 (SGLT-2) and glucagon-like peptide-1 (GLP-1) receptor agonists. Apart from reducing glycaemia, these classes were reported to have other beneficial effects for the cardiovascular and renal systems, such as weight loss and blood pressure reduction. Most importantly, in contrast to all previous studies with anti-diabetic agents, a series of recent randomized, placebo-controlled outcome trials showed that SGLT-2 inhibitors and GLP-1 receptor agonists are able to reduce cardiovascular events and all-cause mortality, as well as progression of renal disease, in patients with type 2 DM. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of SGLT-2 inhibitors and GLP-1 analogues, analyses the potential mechanisms involved in these actions and discusses their place in the treatment of patients with CKD and DM.
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Diabetes Mellitus Tipo 2/complicaciones , Receptor del Péptido 1 Similar al Glucagón/agonistas , Cardiopatías/prevención & control , Riñón/efectos de los fármacos , Insuficiencia Renal Crónica/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Progresión de la Enfermedad , Péptido 1 Similar al Glucagón , Cardiopatías/complicaciones , Humanos , Hipoglucemiantes/uso terapéutico , Guías de Práctica Clínica como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Renal Crónica/complicaciones , Sociedades Médicas , Pérdida de PesoRESUMEN
An increased risk of cardiovascular disease, independent of conventional risk factors, is present even at minor levels of renal impairment and is highest in patients with end-stage renal disease (ESRD) requiring dialysis. Renal dysfunction changes the level, composition and quality of blood lipids in favour of a more atherogenic profile. Patients with advanced chronic kidney disease (CKD) or ESRD have a characteristic lipid pattern of hypertriglyceridaemia and low HDL cholesterol levels but normal LDL cholesterol levels. In the general population, a clear relationship exists between LDL cholesterol and major atherosclerotic events. However, in patients with ESRD, LDL cholesterol shows a negative association with these outcomes at below average LDL cholesterol levels and a flat or weakly positive association with mortality at higher LDL cholesterol levels. Overall, the available data suggest that lowering of LDL cholesterol is beneficial for prevention of major atherosclerotic events in patients with CKD and in kidney transplant recipients but is not beneficial in patients requiring dialysis. The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Lipid Management in CKD provides simple recommendations for the management of dyslipidaemia in patients with CKD and ESRD. However, emerging data and novel lipid-lowering therapies warrant some reappraisal of these recommendations.
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Dislipidemias/sangre , Dislipidemias/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de PCSK9 , Insuficiencia Renal Crónica/fisiopatología , Productos Biológicos/uso terapéutico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Proteínas de Transferencia de Ésteres de Colesterol/antagonistas & inhibidores , Descubrimiento de Drogas , Dislipidemias/complicaciones , Dislipidemias/epidemiología , Ácidos Grasos Omega-3/uso terapéutico , Ácidos Fíbricos/uso terapéutico , Tasa de Filtración Glomerular , Humanos , Metabolismo de los Lípidos , Guías de Práctica Clínica como Asunto , Insuficiencia Renal Crónica/complicacionesRESUMEN
In 2018, World Kidney Day (WKD) and International Women's Day coincide. The WKD editorial focuses on women's kidney health. The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2015 summary provides an excellent snapshot of renal replacement therapy (RRT) epidemiology and women in Europe. The WKD editorial reports a lower incidence of RRT in women in major registries and potential limitations to women's access to transplantation. What is the situation in Europe? In Europe, the incidence of RRT is also lower in women: 38% of incident RRT patients are women. Does it represent milder chronic kidney disease (CKD) in women or barriers to RRT access? The question arises from the higher prevalence of CKD Stages G3-G5 in women than in men. However, in some European countries, such as Spain, non-dialysis CKD Stages G4-G5 is less frequent in women than in men, recapitulating the difference in RRT incidence. In the ERA-EDTA Registry, the incidence of transplantation as a first modality on Day 1 was slightly higher for women and survival on RRT was similar for women and men in the first 3 months, but an intergender gap favouring women increased as RRT vintage increased. However, women on RRT are worse off regarding survival when compared with women in the general population than men on RRT compared with men in the general population. In conclusion, the ERA-EDTA Registry Annual Report 2015 and European epidemiology data suggest a lower incidence of end-stage kidney disease in women, no gender differences in access to transplantation and better RRT survival in women.
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The term acute tubular necrosis was thought to represent a misnomer derived from morphological studies of human necropsies and necrosis was thought to represent an unregulated passive form of cell death which was not amenable to therapeutic manipulation. Recent advances have improved our understanding of cell death in acute kidney injury. First, apoptosis results in cell loss, but does not trigger an inflammatory response. However, clumsy attempts at interfering with apoptosis (e.g. certain caspase inhibitors) may trigger necrosis and, thus, inflammation-mediated kidney injury. Second, and most revolutionary, the concept of regulated necrosis emerged. Several modalities of regulated necrosis were described, such as necroptosis, ferroptosis, pyroptosis and mitochondria permeability transition regulated necrosis. Similar to apoptosis, regulated necrosis is modulated by specific molecules that behave as therapeutic targets. Contrary to apoptosis, regulated necrosis may be extremely pro-inflammatory and, importantly for kidney transplantation, immunogenic. Furthermore, regulated necrosis may trigger synchronized necrosis, in which all cells within a given tubule die in a synchronized manner. We now review the different modalities of regulated necrosis, the evidence for a role in diverse forms of kidney injury and the new opportunities for therapeutic intervention.
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Necrosis Tubular Aguda/patología , Terapia Molecular Dirigida/métodos , Necrosis/fisiopatología , Animales , Apoptosis , Oxalato de Calcio/toxicidad , Cisplatino/toxicidad , Citocinas/fisiología , Evaluación Preclínica de Medicamentos , Ácido Fólico/toxicidad , Humanos , Riñón/irrigación sanguínea , Necrosis Tubular Aguda/inducido químicamente , Necrosis Tubular Aguda/tratamiento farmacológico , Ratones , Ratones Noqueados , Proteínas de Transporte de Membrana Mitocondrial/fisiología , Poro de Transición de la Permeabilidad Mitocondrial , Modelos Biológicos , Necrosis/clasificación , Necrosis/tratamiento farmacológico , Necrosis/inmunología , Daño por Reperfusión/patología , Terminología como AsuntoRESUMEN
La hiponatremia se define como una concentración sérica de sodio <135mmol/L y es el trastorno hidroelectrolítico más frecuente en la práctica clínica. La hiponatremia puede causar un amplio espectro de síntomas clínicos, desde sutiles hasta graves o incluso mortales, y se asocia con aumento de la morbimortalidad y prolongación de la estancia hospitalaria. A pesar de ello, el manejo de los pacientes con hiponatremia sigue siendo problemático. La prevalencia de hiponatremia en enfermedades muy diferentes y su manejo por muy diversos especialistas han fomentado la existencia de protocolos de diagnóstico y tratamiento muy diversos, que varían con la especialidad y la institución. La Sociedad Europea de Medicina Intensiva (ESICM), la Sociedad Europea de Endocrinología (ESE) y la Asociación Renal Europea-Asociación Europea de Diálisis y Trasplante (ERA-EDTA), representada por la European Renal Best Practices (ERBP), han desarrollado la guía de práctica clínica sobre el enfoque diagnóstico y tratamiento de la hiponatremia como una empresa conjunta de las 3 sociedades que representan a los especialistas con un interés natural en la hiponatremia, a fin de ofrecer una visión común y holística del abordaje del problema. Además de ofrecer un enfoque riguroso en la metodología y la evaluación de la evidencia, el documento está centrado en resultados importantes para el paciente y en facilitar una herramienta útil para los médicos en la práctica clínica cotidiana. Presentamos ahora una versión abreviada de las recomendaciones y sugerencias sobre el diagnóstico y el tratamiento de la hiponatremia recogidas en la guía complete (AU)
Hyponatremia, defined as a serum sodium concentration <135mmol/l, is the most common water-electrolyte imbalance encountered in clinical practice. It can lead to a wide spectrum of clinical symptoms, from mild to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay. Despite this, the management of hyponatremia patients remains problematic. The prevalence of hyponatremia in a wide variety of conditions and the fact that hyponatremia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution- and specialty-based approaches to diagnosis and treatment. To obtain a common and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA), represented by European Renal Best Practice (ERBP), have developed clinical practice guidelines on the diagnostic approach and treatment of hyponatremia as a joint venture of 3 societies representing specialists with a natural interest in hyponatremia. In addition to a rigorous approach to the methodology and evaluation of the evidence, the document focuses on patient-positive outcomes and on providing a useful tool for clinicians involved in everyday practice. In this article, we present an abridged version of the recommendations and suggestions for the diagnosis and treatment of hyponatremia extracted from the full guide (AU)
Asunto(s)
Humanos , Hiponatremia/diagnóstico , Hiponatremia/terapia , Índice de Severidad de la Enfermedad , Evaluación de Síntomas/métodos , Síndrome de Secreción Inadecuada de ADH/etiologíaRESUMEN
Hyponatremia, defined as a serum sodium concentration <135mmol/l, is the most common water-electrolyte imbalance encountered in clinical practice. It can lead to a wide spectrum of clinical symptoms, from mild to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay. Despite this, the management of hyponatremia patients remains problematic. The prevalence of hyponatremia in a wide variety of conditions and the fact that hyponatremia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution- and specialty-based approaches to diagnosis and treatment. To obtain a common and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA), represented by European Renal Best Practice (ERBP), have developed clinical practice guidelines on the diagnostic approach and treatment of hyponatremia as a joint venture of 3societies representing specialists with a natural interest in hyponatremia. In addition to a rigorous approach to the methodology and evaluation of the evidence, the document focuses on patient-positive outcomes and on providing a useful tool for clinicians involved in everyday practice. In this article, we present an abridged version of the recommendations and suggestions for the diagnosis and treatment of hyponatremia extracted from the full guide.