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Are prolyl-hydroxylase inhibitors potential alternative treatments for anaemia in patients with chronic kidney disease?
Locatelli, F, Del Vecchio, L
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(6):926-932
Abstract
Prolyl-hydroxylase (PHD) inhibitors (PHD-I) are the most appealing drugs undergoing clinical development for the treatment of anaemia in patients with chronic kidney disease. PHD inhibition mimics the exposure of the body to hypoxia and activates the hypoxia-inducible factor system. Among many other pathways, this activation promotes the production of endogenous erythropoietin (EPO) and the absorption and mobilization of iron. PHD-I are given orally and, differing from erythropoiesis-stimulating agents (ESAs), they correct and maintain haemoglobin levels by stimulating endogenous EPO production. Their efficacy and safety are supported by several Phases I and II studies with relatively short follow-up. This class of drugs has the potential to have a better safety profile than ESAs and there may be additional advantages for cardiovascular disease (CVD), osteoporosis and metabolism. However, possible adverse outcomes are feared. These span from the worsening or occurrence of new cancer, to eye complications or pulmonary hypertension. The data from the ongoing Phase III studies are awaited to better clarify the long-term safety and possible advantages of PHD-I.
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[Chronic kidney disease-a cardiovascular high-risk constellation].
Speer, T, Schunk, SJ, Fliser, D
Der Internist. 2020;(4):340-348
Abstract
Chronic kidney disease (CKD) is associated with substantial cardiovascular morbidity and mortality. This is mediated by the high prevalence of traditional cardiovascular risk factors in patients with CKD such as arterial hypertension and diabetes mellitus, but also by the presence of CKD-specific so-called nontraditional cardiovascular risk factors such as vascular calcification, uremic toxins, uremic dyslipidemia as well as inflammation and oxidative stress. Therefore, the primary and secondary prevention of cardiovascular disease represents an integral part of nephrology. This entails optimal control of blood pressure and diabetes, therapy of the uremic dyslipidemia as well as lifestyle-modifying factors such as weight reduction and smoking cessation.
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3.
The transition clinic in chronic kidney disease care.
Evans, M, Lopau, K
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(Suppl 2):ii4-ii10
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Abstract
People with advanced chronic kidney disease and evidence of progression have a high risk of renal replacement therapy. Specialized transition clinics could offer a better option for preparing these patients for dialysis, transplantation or conservative care. This review focuses on the different aspects of such transition clinics. We discuss which patients should be referred to these units and when referral should take place. Patient involvement in the decision-making process is important and requires unbiased patient education. There are many themes, both patient-centred and within the healthcare structure, that will influence the process of shared decision-making and the modality choice. Aspects of placing an access for haemodialysis and peritoneal dialysis are reviewed. Finally, we discuss the importance of pre-emptive transplantation and a planned dialysis start, all with a focus on multidisciplinary collaboration at the transition clinic.
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Plant-Dominant Low-Protein Diet for Conservative Management of Chronic Kidney Disease.
Kalantar-Zadeh, K, Joshi, S, Schlueter, R, Cooke, J, Brown-Tortorici, A, Donnelly, M, Schulman, S, Lau, WL, Rhee, CM, Streja, E, et al
Nutrients. 2020;(7)
Abstract
Chronic kidney disease (CKD) affects >10% of the adult population. Each year, approximately 120,000 Americans develop end-stage kidney disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates, exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6–0.8 g/kg/day composed of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, is promising and consistent with the precision nutrition. The scientific premise of the PLADO stems from the observations that high protein diets with high meat intake not only result in higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of constipation with resulting hyperkalemia from the typical low fiber intake. A plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.
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Let Them Eat Healthy: Can Emerging Potassium Binders Help Overcome Dietary Potassium Restrictions in Chronic Kidney Disease?
Sussman, EJ, Singh, B, Clegg, D, Palmer, BF, Kalantar-Zadeh, K
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2020;(6):475-483
Abstract
Potassium-rich foods might provide many health benefits even to people who have declining renal function. The barrier to obtaining these health benefits has long been the concern over hyperkalemia. There are new and novel treatment options available which may enable patients with chronic kidney disease to obtain the health benefits of eating a diet that contains foods such as fruits and vegetables which are high in potassium while reducing the risk of hyperkalemia. We conclude by emphasizing the need for clinical trials with patients on hemodialysis to directly compare the current standard of care, including a potassium-restricted diet, to a potassium-liberalized diet with a potassium binder. The outcome measures would be serum potassium (<5.3 mmol/L), assessments of acidosis, blood pressure, constipation, glycemic control, overhydration, and azotemia, all of which might change in a favorable direction with vegetarian diets as well as quality of life and satisfaction.
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Series: Implications of the recent CVOTs in type 2 diabetes: Impact on guidelines: The endocrinologist point of view.
Scheen, AJ
Diabetes research and clinical practice. 2020;:107726
Abstract
The management of type 2 diabetes mellitus (T2DM) essentially consists in controlling hyperglycaemia, together with other vascular risk factors, in order to reduce the incidence and severity of diabetic complications. Whereas glucose control using classical glucose-lowering agents (except perhaps metformin) largely fails to reduce cardiovascular disease (CVD), two new pharmacological classes, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter type 2 inhibitors (SGLT2is), have proven their ability to reduce major cardiovascular events in patients with established CVD. Furthermore, SGLT2is reduced the risk of hospitalisation for heart failure and the progression of renal disease. According to the 2018 ADA-EASD consensus report, the choice of a second agent to be added to metformin should now be driven by the presence or not of atherosclerotic CVD, heart failure or renal disease, all conditions that should promote the use of a SGLT2i or a GLP-1 RA with proven efficacy. Thus endocrinologists have to face a new paradigm in the management of T2DM, with a shift from a primary objective of glucose control without inducing hypoglycaemia and weight gain to a goal of cardiovascular and renal protection, largely independent of glucose control. Of note, however, the latter remains crucial to reduce the risk of microangiopathy.
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Eating Out for Patients With Chronic Kidney Disease.
Martin, T, Pringle, L
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2020;(1):e1-e4
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Advances in exercise therapy in predialysis chronic kidney disease, hemodialysis, peritoneal dialysis, and kidney transplantation.
Wilkinson, TJ, McAdams-DeMarco, M, Bennett, PN, Wilund, K, ,
Current opinion in nephrology and hypertension. 2020;(5):471-479
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Abstract
PURPOSE OF REVIEW Chronic kidney disease (CKD) is characterized by poor levels of physical activity which contribute to increased morbidity across the disease trajectory. The short nature, small samples, and poor methodology across most studies have failed to translate the role of exercise in CKD into its adoption as a frontline adjunct therapeutic option. This review focuses on recent advances surrounding the benefits of exercise interventions across the CKD spectrum. RECENT FINDINGS Key recent advances in exercise studies have focused on the efficacy of novel intervention strategies across the CKD spectrum. These include high-intensity interval training, virtual reality gaming, intradialytic yoga, electrical stimulation of muscles, blood flow restriction training, and protocols combining exercise with nutritional supplementation. Research is also beginning to explore the role of prehabilitation for patients prior to dialysis and kidney transplantation. SUMMARY Studies continue to demonstrate wide-ranging benefits of exercise across CKD; however, implementation of exercise remains scarce. Future research needs include evaluating the efficacy of larger and/or more comprehensive interventions on clinically important outcomes. It is hoped with increasing global evidence, high-quality clinical studies, and sustained clinician and patient engagement, exercise programs will become better prioritized in the nephrology field.
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Design and optimization strategies for the development of new drugs that treat chronic kidney disease.
Ramos, AM, Fernández-Fernández, B, Pérez-Gómez, MV, Carriazo Julio, SM, Sanchez-Niño, MD, Sanz, A, Ruiz-Ortega, M, Ortiz, A
Expert opinion on drug discovery. 2020;(1):101-115
Abstract
Introduction: Chronic kidney disease (CKD) is characterized by increased risks of progression to end-stage kidney disease requiring dialysis and cardiovascular mortality, predicted to be among the five top causes of death by 2040. Only the design and optimization of novel strategies to develop new drugs to treat CKD will contain this trend. Current therapy for CKD includes nonspecific therapy targeting proteinuria and/or hypertension and cause-specific therapies for diabetic kidney disease, autosomal dominant polycystic kidney disease, glomerulonephritides, Fabry nephropathy, hemolytic uremic syndrome and others.Areas covered: Herein, the authors review the literature on new drugs under development for CKD as well as novel design and development strategies.Expert opinion: New therapies for CKD have become a healthcare priority. Emerging therapies undergoing clinical trials are testing expanded renin-angiotensin system blockade with double angiotensin receptor/endothelin receptor blockers, SGLT2 inhibition, and targeting inflammation, the immune response, fibrosis and the Nrf2 transcription factor. Emerging therapeutic targets include cell senescence, complement activation, Klotho expression preservation and microbiota. Novel approaches include novel model systems that can be personalized (e.g. organoids), unbiased systems biology-based identification of new therapeutic targets, drug databases that speed up drug identification and repurposing, nanomedicines that improve drug delivery and RNA targeting to expand the number of targetable proteins.
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[SGLT2 inhibitors, beyond glucose-lowering effect: impact on nephrology clinical practice].
Costanza, G, Pesce, F, Forcella, M, Leonardi, G, Seminara, G, Di Natale, E, Granata, A
Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia. 2020;(4)
Abstract
Epidemiological data show an increasing diffusion of diabetes mellitus worldwide. In the diabetic subject, the risk of onset of chronic kidney disease (CKD) and its progression to the terminal stage remain high, despite current prevention and treatment measures. Although SGLT2 inhibitors have been approved as blood glucose lowering drugs, they have shown unexpected and surprising cardioprotective and nephroprotective efficacy. The multiple underlying mechanisms of action are independent and go beyond glycemic lowering. Hence, it has been speculated to extend the use of these drugs also to subjects with advanced stages of CKD, who were initially excluded because of the expected limited glucose-lowering effect. Non-diabetic patients could also benefit from the favorable effects of SGLT2 inhibitors: subjects with renal diseases with different etiologies, heart failure, high risk or full-blown cardiovascular disease. In addition, these drugs have a good safety profile, but several post-marketing adverse event have been reported. The ongoing clinical trials will provide clearer information on efficacy, strength and safety of these molecules. The purpose of this review is to analyze the available evidence and future prospects of SGLT2 inhibitors, which could be widely used in nephrology clinical practice.