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A PRoliferation Inducing Ligand (APRIL) is a key member of the tumor necrosis factor (TNF)-superfamily of cytokines, and plays a central role in B cell survival, proliferation and immunoglobulin class switching. Recently, there has been increasing interest in the role of APRIL and the related cytokine B cell activating factor (BAFF) in several glomerular diseases, due to their importance in the above processes. The therapeutic inhibition of APRIL represents a potentially attractive immunomodulatory approach, that may abrogate deleterious host immune responses in autoimmune diseases while leaving other important functions of humoral immunity intact, such as memory B cell function and responses to vaccination, in contrast to B cell depleting strategies. In this review, we describe the physiological roles of APRIL in B cell development and their relevance to glomerular diseases, and outline emerging clinical trial data studying APRIL inhibition, with a focus on IgA nephropathy where the clinical development of APRIL inhibitors is in its most advanced stage.
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DESCRIPTION: The KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease is an update of the 2020 guideline from Kidney Disease: Improving Global Outcomes (KDIGO). METHODS: The KDIGO Work Group updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the Work Group used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and expert judgment to develop consensus practice points. New evidence led to updating of recommendations in the chapters Comprehensive Care in Patients With Diabetes and CKD (Chapter 1) and Glucose-Lowering Therapies in Patients With T2D and CKD (Chapter 4). New evidence did not change recommendations in the chapters Glycemic Monitoring and Targets in Patients With Diabetes and CKD (Chapter 2), Lifestyle Interventions in Patients With Diabetes and CKD (Chapter 3), and Approaches to Management of Patients With Diabetes and CKD (Chapter 5). RECOMMENDATIONS: The updated guideline includes 13 recommendations and 52 practice points for clinicians caring for patients with diabetes and chronic kidney disease (CKD). A focus on preserving kidney function and maintaining well-being is recommended using a layered approach to care, starting with a foundation of lifestyle interventions, self-management, and first-line pharmacotherapy (such as sodium-glucose cotransporter-2 inhibitors) demonstrated to improve clinical outcomes. To this are added additional drugs with heart and kidney protection, such as glucagon-like peptide-1 receptor agonists and nonsteroidal mineralocorticoid receptor antagonists, and interventions to control risk factors for CKD progression and cardiovascular events, such as blood pressure, glycemia, and lipids.
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Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Riñón , GlucosaRESUMEN
As the rate of natural disasters and other devastating events caused by human activities increases, the burden on the health and well-being of those affected by kidney disease has been immeasurable. Health system preparedness, which involves creating a resilient system that is able to deal with the health needs of the entire community during times of unexpected disruptions to usual care, has become globally important. In the wake of the COVID-19 pandemic, there is a heightened awareness of the amplification of negative effects on the renal community. Paradoxically, the complex medical needs of those who have kidney diseases are not met by systems handling crises, often compounded by an acute increase in burden via new patients as a result of the crisis itself. Disruptions in kidney care as a result of unexpected events are becoming more prevalent and likely to increase in the years to come. It is therefore only appropriate that the theme for this year's World Kidney Day will focus on Kidney Health for All: preparedness for the unexpected in supporting the vulnerable.
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COVID-19 , Planificación en Desastres , Enfermedades Renales , Humanos , Pandemias , RiñónRESUMEN
Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams.
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Fallo Renal Crónico , Diálisis Peritoneal , Insuficiencia Renal , Humanos , Hemodiálisis en el Domicilio , Calidad de Vida , Diálisis Renal , Fallo Renal Crónico/terapiaRESUMEN
Pain is prevalent among patients with diabetes and chronic kidney disease (CKD). The management of chronic pain in these patients is limited by nephrotoxicity of commonly used drugs including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids. Since previous studies implicated endothelin-1 in pain nociception, our post hoc analysis of the SONAR trial assessed the association between the endothelin receptor antagonist atrasentan and pain and prescription of analgesics. SONAR was a randomized, double-blind, placebo-controlled clinical trial that recruited participants with type 2 diabetes and CKD (estimated glomerular filtration rate 25-75 ml/min/1.73 m2; urinary albumin-to-creatinine ratio 300-5000 mg/g). Participants were randomized to receive atrasentan or placebo (1834 each arm). The main outcome was pain-related adverse events (AEs) reported by investigators. We applied Cox regression to assess the effect of atrasentan compared to placebo on the risk of the first reported pain-related AE and, secondly, first prescription of analgesics. We used the Anderson-Gill method to assess effects on all (first and subsequent) pain-related AEs. During 2.2-year median follow-up, 1183 pain-related AEs occurred. Rates for the first pain-related event were 138.2 and 170.2 per 1000 person-years in the atrasentan and placebo group respectively (hazard ratio 0.82 [95% confidence interval 0.72-0.93]). Atrasentan also reduced the rate of all (first and subsequent) pain-related AEs (rate ratio 0.80 [0.70-0.91]). These findings were similar after accounting for competing risk of death (sub-hazard ratio 0.81 [0.71-0.92]). Patients treated with atrasentan initiated fewer analgesics including NSAIDs and opioids compared to placebo during follow-up (hazard ratio = 0.72 [0.60-0.88]). Thus, atrasentan was associated with reduced pain-related events and pain-related use of analgesics in carefully selected patients with type 2 diabetes and CKD.
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Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Humanos , Antiinflamatorios no Esteroideos , Atrasentán/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Antagonistas de los Receptores de Endotelina/efectos adversos , Dolor/tratamiento farmacológico , Dolor/etiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Método Doble CiegoRESUMEN
BACKGROUND: Insulin resistance (IR) is a pathophysiologic hallmark of type 2 diabetes and associated with the presence of chronic kidney disease (CKD). Experimental studies suggest that endothelin-1 increases IR. We assessed the association between IR and cardio-renal outcomes and the effect of the selective endothelin receptor antagonist atrasentan on IR in patients with type 2 diabetes and CKD. METHODS: We used data from the RADAR and SONAR trials that recruited participants with type 2 diabetes and CKD [eGFR 25-75 mL/min/1.73 m², urine albumin-to-creatinine ratio of 300-5000 mg/g]. IR was calculated using the homeostatic model assessment (HOMA-IR). The association between HOMA-IR and the pre-specified cardio-renal outcomes was assessed using multivariable Cox proportional hazards regression, and effects of atrasentan on HOMA-IR by a linear mixed effect model. RESULTS: In the SONAR trial, each log-unit increase in HOMA-IR was associated with an increased risk of the composite cardio-renal outcome [hazard ratio 1.32 (95%CI 1.09,1.60; p = 0.004)], kidney outcome [hazard ratio 1.30 (95%CI 1.00,1.68; p-value = 0.048)], and the kidney or all-cause mortality outcome [hazard ratio 1.25 (95%CI 1.01,1.55; p-value = 0.037)]. After 12 weeks treatment in the RADAR trial (N = 123), atrasentan 0.75 mg/day and 1.25 mg/day compared to placebo reduced HOMA-IR by 19.1 (95%CI -17.4, 44.3) and 26.7% (95%CI -6.4, 49.5), respectively. In the SONAR trial (N = 1914), atrasentan 0.75 mg/day compared to placebo reduced HOMA-IR by 9.6% (95%CI 0.6, 17.9). CONCLUSIONS: More severe IR is associated with increased risk of cardio-renal outcomes. The endothelin receptor antagonist atrasentan reduced IR. TRIAL REGISTRATION: RADAR trial (Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With AtRasentan): NCT01356849. SONAR trial (The Study Of Diabetic Nephropathy With AtRasentan) NCT01858532.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Insuficiencia Renal Crónica , Humanos , Atrasentán/efectos adversos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Riñón , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/epidemiología , Antagonistas de los Receptores de Endotelina/efectos adversosRESUMEN
Recent clinical studies have demonstrated the effectiveness of SGLT-2 inhibitors in reducing the risks of cardiovascular and renal events in both patients with and without type 2 diabetes mellitus. Consequently, many international guidelines have begun advocating for the use of SGLT-2 inhibitors for the purpose of organ protection rather than as simply a glucose-lowering agent. However, despite the consistent clinical benefits and available strong guideline recommendations, the utilization of SGLT-2 inhibitors have been unexpectedly low in many countries, a trend which is much more noticeable in low resource settings. Unfamiliarity with the recent focus in their organ protective role and clinical indications; concerns with potential adverse effects of SGLT-2 inhibitors, including acute kidney injury, genitourinary infections, euglycemic ketoacidosis; and their safety profile in elderly populations have been identified as deterring factors to their more widespread use. This review serves as a practical guide to clinicians managing patients who could benefit from SGLT-2 inhibitors treatment and instill greater confidence in the initiation of these drugs, with the aim of optimizing their utilization rates in high-risk populations.
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Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Anciano , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Glucemia , Factores de RiesgoRESUMEN
The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (CKD) represents a focused update of the KDIGO 2020 guideline on the topic. The guideline targets a broad audience of clinicians treating people with diabetes and CKD. Topic areas for which recommendations are updated based on new evidence include Chapter 1: Comprehensive care in patients with diabetes and CKD and Chapter 4: Glucose-lowering therapies in patients with type 2 diabetes (T2D) and CKD. The content of previous chapters on Glycemic monitoring and targets in patients with diabetes and CKD (Chapter 2), Lifestyle interventions in patients with diabetes and CKD (Chapter 3), and Approaches to management of patients with diabetes and CKD (Chapter 5) has been deemed current and was not changed. This guideline update was developed according to an explicit process of evidence review and appraisal. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence, and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, and areas for which additional research is needed are presented.
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Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia , GlucosaRESUMEN
There have been significant advances in the understanding of peritoneal dialysis (PD) in the last 40 years, and uptake of PD as a modality of kidney replacement therapy is increasing worldwide. PD fluids, therefore, remains the lifeline for patients on this treatment. Developing these fluids to be efficacious in solute clearance and ultrafiltration, with minimal adverse consequences to peritoneal membrane health and systemic effects is a key requirement. Since the first PD fluid produced in 1959, modifications to PD fluids have been made. Nonetheless, the search for that ideal PD fluid remains elusive. Understanding the components of PD fluids is a key aspect of optimizing the successful delivery of PD, allowing for individualized PD prescription. Glucose remains an integral component of PD fluids; however, its deleterious effects continue to be the impetus for the search of an alternative osmotic agent, and icodextrin remains the main alternative. More biocompatible PD fluids have been developed and have shown benefits in preserving residual kidney function. However, high cost and reduced accessibility remain deterrents to its widespread clinical use in many countries. Large-scale clinical trials are necessary and very much awaited to improve the narrow spectrum of PD fluids available for clinical use.
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INTRODUCTION: This review article reports clinical outcomes and performance indicators of patients with kidney failure (KF) and acute kidney injuries (AKI) in Association of South East Asian Nations (ASEAN) countries. METHODOLOGY: Association of South East Asian Nations data, segregated by income status, from national registries and literature were collated, compared and benchmarked against international references. RESULTS: The national incidence and prevalence of treated KF ranged from 172 to 479 per million population (pmp) and 36-2255 pmp, respectively. Brunei (79%), Malaysia (66%) and Singapore (66%) had world-leading proportions of diabetes-related KF. Hemodialysis (HD), Peritoneal Dialysis (PD) and transplant accounted for 68-100%, 0-27% and 0-18% of all KF replacement therapy, respectively. Transplant patient survival was superior with 90%-93% at 5 years and 71%-90% at 10 years, compared to PD (44%-54%) and HD (53-64%) at 5 years. Higher-income countries were able to achieve good anemia control, HD and PD adequacy targets, while usage of arteriovenous fistula in HD varied from 70% to 85%. Acute Kidney Injury rates ranged from 24.2% to 49.2% of high-dependency admissions. Lower incidences of PD peritonitis and HD catheter-related Bloodstream Infections; and PD-favouring quality-of-life were evident in higher-income countries. CONCLUSION: Association of South East Asian Nations has a challenging burden of kidney disease, with extremely high incidence, prevalence, DM-related KF and AKI rates. The magnitude of the prevailing problem calls for the creation of a regional society under the auspices of ASEAN with a shared perspective of universal, equitable and charitable access to quality renal care; consistent with the founding premises and healthcare initiatives of ASEAN.
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Lesión Renal Aguda , Fallo Renal Crónico , Diálisis Peritoneal , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/terapia , Humanos , Fallo Renal Crónico/terapia , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , Terapia de Reemplazo RenalRESUMEN
DESCRIPTION: The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed a clinical practice guideline in 2020 for the management of patients with diabetes and chronic kidney disease (CKD). METHODS: The KDIGO Work Group (WG) was tasked with developing the guideline for diabetes management in CKD. It defined the scope of the guideline, gathered evidence, determined systematic review topics, and graded evidence that had been summarized by an evidence review team. The English-language literature searches, which were initially done through October 2018, were updated in February 2020. The WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of the recommendations. Expert judgment was used to develop consensus practice points supplementary to the evidence-based graded recommendations. The guideline document underwent open public review. Comments from various stakeholders, subject matter experts, and industry and national organizations were considered before the document was finalized. RECOMMENDATIONS: The guideline includes 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and CKD. This synopsis focuses on the key recommendations pertinent to the following issues: comprehensive care needs, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and educational and integrated care approaches.
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Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Insuficiencia Renal Crónica/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Insuficiencia Renal Crónica/terapiaRESUMEN
Outcomes relevant to treatment decision-making are inconsistently reported in trials involving glomerular disease. Here, we sought to establish a consensus-derived set of critically important outcomes designed to be reported in all future trials by using an online, international two-round Delphi survey in English. To develop this, patients with glomerular disease, caregivers and health professionals aged 18 years and older rated the importance of outcomes using a Likert scale and a Best-Worst scale. The absolute and relative importance was assessed and comments were analyzed thematically. Of 1198 participants who completed Round 1, 734 were patients/caregivers while 464 were health care professionals from 59 countries. Of 700 participants that completed Round 2, 412 were patients/caregivers and 288 were health care professionals. Need for dialysis or transplant, kidney function, death, cardiovascular disease, remission-relapse and life participation were the most important outcomes to patients/caregivers and health professionals. Patients/caregivers rated patient-reported outcomes higher while health care professionals rated hospitalization, death and remission/relapse higher. Four themes explained the reasons for their priorities: confronting death and compounded suffering, focusing on specific targets in glomerular disease, preserving meaning in life, and fostering self-management. Thus, consistent reporting of these critically important outcomes in all trials involving glomerular disease is hoped to improve patient-centered decision-making.
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Cuidadores , Diálisis Renal , Adulto , Técnica Delphi , Humanos , Evaluación de Resultado en la Atención de Salud , Encuestas y CuestionariosRESUMEN
The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases is an update to the KDIGO 2012 guideline. The aim is to assist clinicians caring for individuals with glomerulonephritis (GN), both adults and children. The scope includes various glomerular diseases, including IgA nephropathy and IgA vasculitis, membranous nephropathy, nephrotic syndrome, minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), infection-related GN, antineutrophil cytoplasmic antibody (ANCA) vasculitis, lupus nephritis, and anti-glomerular basement membrane antibody GN. In addition, this guideline will be the first to address the subtype of complement-mediated diseases. Each chapter follows the same format providing guidance related to diagnosis, prognosis, treatment, and special situations. The goal of the guideline is to generate a useful resource for clinicians and patients by providing actionable recommendations based on evidence syntheses, with useful infographics incorporating views from experts in the field. Another aim is to propose research recommendations for areas where there are gaps in knowledge. The guideline targets a broad global audience of clinicians treating GN while being mindful of implications for policy and cost. Development of this guideline update followed an explicit process whereby treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the quality of the evidence and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, with areas of future research also presented.
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Glomerulonefritis por IGA , Glomerulonefritis Membranosa , Glomerulonefritis , Nefrosis Lipoidea , Adulto , Niño , Glomerulonefritis/diagnóstico , Glomerulonefritis/terapia , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/terapia , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/tratamiento farmacológico , Humanos , RiñónRESUMEN
There is a huge gap between the number of patients worldwide requiring versus those actually receiving safe, sustainable, and equitable care for kidney failure. To address this, the International Society of Nephrology coordinated the development of a Strategic Plan for Integrated Care of Patients with Kidney Failure. Implementation of the plan will require engagement of the whole kidney community over the next 5-10 years.
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Prestación Integrada de Atención de Salud , Nefrología , Insuficiencia Renal , HumanosRESUMEN
THE KIDNEY DISEASE: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease represents the first KDIGO guideline on this subject. The guideline comes at a time when advances in diabetes technology and therapeutics offer new options to manage the large population of patients with diabetes and chronic kidney disease (CKD) at high risk of poor health outcomes. An enlarging base of high-quality evidence from randomized clinical trials is available to evaluate important new treatments offering organ protection, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. The goal of the new guideline is to provide evidence-based recommendations to optimize the clinical care of people with diabetes and CKD by integrating new options with existing management strategies. In addition, the guideline contains practice points to facilitate implementation when insufficient data are available to make well-justified recommendations or when additional guidance may be useful for clinical application. The guideline covers comprehensive care of patients with diabetes and CKD, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and self-management and health systems approaches to management of patients with diabetes and CKD.
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Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hipoglucemiantes/uso terapéutico , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapiaRESUMEN
Asia is the largest and most populated continent in the world, with a high burden of kidney failure. In this Policy Forum article, we explore dialysis care and dialysis funding in 17 countries in Asia, describing conditions in both developed and developing nations across the region. In 13 of the 17 countries surveyed, diabetes is the most common cause of kidney failure. Due to great variation in gross domestic product per capita across Asian countries, disparities in the provision of kidney replacement therapy (KRT) exist both within and between countries. A number of Asian nations have satisfactory access to KRT and have comprehensive KRT registries to help inform practices, but some do not, particularly among low- and low-to-middle-income countries. Given these differences, we describe the economic status, burden of kidney failure, and cost of KRT across the different modalities to both governments and patients and how changes in health policy over time affect outcomes. Emerging trends suggest that more affluent nations and those with universal health care or access to insurance have much higher prevalent dialysis and transplantation rates, while in less affluent nations, dialysis access may be limited and when available, provided less frequently than optimal. These trends are also reflected by an association between nephrologist prevalence and individual nations' incomes and a disparity in the number of nephrologists per million population and per thousand KRT patients.
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Fallo Renal Crónico/terapia , Diálisis Renal/estadística & datos numéricos , Asia/epidemiología , Costo de Enfermedad , Países Desarrollados/economía , Países en Desarrollo/economía , Nefropatías Diabéticas/economía , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/terapia , Costos de la Atención en Salud/estadística & datos numéricos , Gastos en Salud/estadística & datos numéricos , Accesibilidad a los Servicios de Salud , Hospitales Privados/economía , Hospitales Privados/estadística & datos numéricos , Hospitales Públicos/economía , Hospitales Públicos/estadística & datos numéricos , Humanos , Cobertura del Seguro/estadística & datos numéricos , Fallo Renal Crónico/economía , Fallo Renal Crónico/epidemiología , Trasplante de Riñón/economía , Trasplante de Riñón/estadística & datos numéricos , Prevalencia , Utilización de Procedimientos y Técnicas/economía , Utilización de Procedimientos y Técnicas/estadística & datos numéricos , Diálisis Renal/economía , Cobertura Universal del Seguro de Salud/estadística & datos numéricosAsunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Insuficiencia Renal Crónica , Humanos , Atrasentán , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Riñón , HígadoRESUMEN
Haemodialysis (HD) was the first procedure that had demonstrated the ability to partially replace renal function, and became the most widely utilized treatment for patients with end-stage renal disease (ESRD). In a great majority of countries around the world, conventional in-centre HD had become the predominant renal replacement therapy, being touted as able to achieve better solute clearance and more successful in attaining euvolemia than patients on peritoneal dialysis. This is despite the antecedent hemodynamic risks, more rapid loss of residual renal function, greater infectious perils, excessive erythropoietin requirements and higher infrastructure costs. In addition, quality of life had been suggested to be worse among patients on HD, though this had been challenged repeatedly. Consequently, the concept of integrated ESRD care over the last few decades had placed HD, as a complementary rather than a competitive treatment modality to the entire armamentarium of renal replacement therapies. Incorporating HD as part of integrated care into health-care policies and national resource planning will become an essential strategy in improving access and outcome to care among the ESRD population. The improvement in technologies and innovation in prescription had brought forth enhanced dialyzer membrane and machine upgrades, and expanded modalities including more frequent HD and haemodiafiltration. While boasting of controversial improvement in outcomes, many of these therapies remain expensive and insurmountable for widespread utility in many countries. In addition, the results of these new technologies had been conflicting across studies, with some even suggesting that they could be detrimental. Therefore, judicial consideration has to be undertaken to appropriate their use in clinical practice.
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Fallo Renal Crónico/terapia , Riñón/fisiopatología , Diálisis Renal/métodos , Diseño de Equipo , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/fisiopatología , Membranas Artificiales , Diálisis Renal/efectos adversos , Diálisis Renal/instrumentación , Resultado del TratamientoRESUMEN
AIM: Studies reporting the association between complement factor H gene rs6677604 polymorphism and susceptibility to IgA nephropathy (IgAN) had yielded inconsistent results. We performed a systematic review and meta-analysis to clarify the association between rs6677604 and IgAN susceptibility, disease severity and chronic progression. METHODS: A comprehensive database search was performed to identify eligible studies. Meta-analyses were performed for rs6677604 allele frequency, genotypes and the association with IgAN susceptibility. RESULTS: 10 studies were included in the systematic review. Among them, four studies containing 10 distinct datasets (15,617 cases and 31,957 controls) were included in the meta-analysis. The pooled frequency of the minor allele (A) was significantly higher in Europeans than in Asians across both IgAN cases and controls, and the frequency of the minor allele (A) in IgAN cases was also significantly lower than that in controls across both European and Asian subgroups. Significant associations were detected between rs6677604 and risk of developing IgAN, when comparing allele A vs. G, genotype AA vs. GG, genotype AA vs. AG and genotype AG vs. GG. In analysis stratified by ethnicity, significant association was only observed in Europeans but not in Asians when comparing AA vs. GG or AA vs. AG. CONCLUSION: Our pooled analysis showed a significant association between rs6677604-(A) allele and IgAN susceptibility, supporting the importance of complement activation in the pathogenesis of IgAN. The presence of rs6677604-(A) allele may be associated with a decreased the risk of IgAN in Europeans, but the association was not confirmed in Asians.
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Glomerulonefritis por IGA/genética , Adulto , Factor H de Complemento/genética , Factor H de Complemento/inmunología , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/etnología , Glomerulonefritis por IGA/inmunología , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Current immunosuppression strategies in the treatment of glomerulonephritides remain unsatisfactory, especially in glomerular diseases that are frequently relapsing or are resistant to treatment. Toxicities associated with the use of drugs with non-specific targets for the immune response result in treatment non-compliance, and increase morbidity and mortality in these patients. Advances in our understanding of the immunopathogenesis of glomerulonephritis and the availability of biologics have led to their successful use in the treatment of immune-mediated glomerular diseases. Biologics are usually very large complex molecules, often produced using recombinant DNA technology and manufactured in a living system such as a microorganism, or plant or animal cells. They are novel agents that can target specific immune cell types, cytokines or immune pathways involved in the pathogenesis of these disorders. It is attractive to consider that, given their specific mode of action, these agents can potentially offer a more directed and effective immunosuppression, with side-effect profiles that are much more desirable. However, there have been few randomized controlled trials comparing biologic agents to conventional immunosuppression, and in many of these studies the side-effect profiles have been disappointingly similar. In this review, we will examine the rationale, efficacy and safety of some commonly used biologics in the treatment of primary and secondary glomerulonephritides. We will also discuss some of the key challenges that may be encountered with the use of biologics in treating glomerulonephritis in the future.