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Management of Anemia in Nondialysis Chronic Kidney Disease: Current Recommendations, Real-World Practice, and Patient Perspectives

2020 , Guedes, Murilo , Robinson, Bruce M. , Obrador, Gregorio , Tong, Allison , Pisoni, Ronald L. , Pecoits-Filho, Roberto

In nondialysis CKD (ND-CKD), anemia is a multifactorial and complex condition in which several dysfunctions dynamically contribute to a reduction in circulating hemoglobin (Hb) levels in red blood cells. Anemia is common in CKD and represents an important and modifiable risk factor for poor clinical outcomes. Importantly, symptoms related to anemia, including reduced physical functioning and fatigue, have been identified as high priorities by patients with CKD. The current management of anemia in ND-CKD (i.e., parameters to initiate treatment, Hb and iron indexes targets, choice of therapies, and effect of treatment on clinical and patient-reported outcomes) remains controversial. In this review article, we explore the epidemiology of anemia in ND-CKD and revise current recommendations and controversies in its management. Exploring data from real-world clinical practices, particularly from the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps), we highlight the current challenges to translating current recommendations to clinical practice, providing patients' perspectives of anemia and how it affects their quality of life. Finally, we summarize recent advances in the field of anemia that may change the way this condition will be managed in the future. Copyright © 2020 by the American Society of Nephrology.

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Nephrology in Mexico

2021 , García-García, Guillermo , Chávez-Iñiguez, Jonathan Samuel , Vázquez-Rangel, Armando , Cervantes-Sánchez, Cynthia Gabriela , Paniagua, Ramón , Valdez-Ortiz, Rafael , Reyes-Acevedo, Rafael , Medeiros, Mara , Aguilar-Kitsu, Maria Alejandra , Muñoz-Arizpe, Ricardo , Obrador, Gregorio , Rubilar-Araya, Ximena

Nephrology in Mexico started in 1955 with the opening of the nephrology department at Mexico’s National Heart Institute, where the first nephrology training program began in 1958. Pediatric nephrology care was first offered at Mexico’s Federico Gomez Children’s Hospital in 1953, among the first pediatric nephrology programs in the world. Kidney transplantation began in 1963 at the IMSS General Hospital. The Sociedad Mexicana de Nefrologia, the first Mexican nephrology society, was established in 1967, followed by the publication of Nefrologia Mexicana, its official journal, in 1980. Chronic kidney disease has emerged as a public health problem in Mexico. However, the fragmentation of the health system has resulted in unequal access to renal replacement therapy. Seguro Popular, a public health-care insurance for the poor, does not cover renal replacement therapy. As a consequence, many uninsured patients refuse dialysis, eventually abandon their treatment, or lose their kidney grafts because sustaining dialysis or immunosuppression becomes unaffordable. The lack of a national dialysis registry results in a vacuum of information on the burden of treated end-stage renal disease and its outcomes. In addition to the high burden of traditional risk factors (i.e., diabetes mellitus), a number of “hotspots” of chronic kidney disease of unknown origin have been recently described in the country. Despite the increased burden of chronic kidney disease, strategies to prevent chronic kidney disease have not been part of the nation’s noncommunicable disease health policies. Chronic kidney disease screening is not part of the National Health Surveys. Peritoneal dialysis continues to be the dialysis modality of choice, although a significant shift to hemodialysis has been observed over the last two decades. The number of nephrologists (9.1 per million population) is insufficient to match the demand imposed by the burden of chronic kidney disease. In conclusion, after 65 years of the beginning of nephrology in Mexico, kidney disease care remains unjust, unequal, and below the quality of international standards. The current infrastructure and resources are insufficient to satisfy the demand of renal care in our society. Therefore, it is important to consider it as a public health priority and to implement a comprehensive program for the prevention and control of this illness. The establishment of a national public policy for the prevention and treatment of chronic kidney disease is urgently needed. © Springer Nature

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The environment and kidney health: challenges and opportunities

2022 , Bharati, Joyita , Zavaleta-Cortijo, Carol , Bressan, Tiana , Shingada, Aakash , Obrador, Gregorio , Sola, Laura , Peiris, David , Miranda, J. Jaime , Jha, Vivekanand

The accelerating environmental degradation as a result of modernisation and climate change is an urgent threat to human health. Environment change can impact kidney health in a variety of ways such as water scarcity, global heating and changing biodiversity. Ever increasing industrialization of health care has a large carbon footprint, with dialysis being a major contributor. There have been calls for all stakeholders to adopt a ‘one health approach’ and develop mitigation and adaptation strategies to combat this challenge. Because of its exquisite sensitivity to various elements of environment change, kidney health can be a risk marker and a therapeutic target for such interventions. In this narrative review, we discuss the various mechanisms through which environmental change is linked to kidney health and the ways that the global kidney health communities can respond to environmental change. ©D.R. © por el sitio: Instituto Nacional de Salud Pública.

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Iron management in chronic kidney disease: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference

2016 , Macdougall, Iain C. , Bircher, Andreas J. , Eckardt, Kai-uwe , Obrador, Gregorio , Pollock, Carol A. , Stenvinkel, Peter , Swinkels, Dorine W. , Wanner, Christoph , Weiss, Günter , Chertow, Glenn M. , Adamson, John W. , Akizawa, Tadao , Anker, Stefan D. , Auerbach, Michael , Bárány, Peter , Besarab, Anatole , Bhandari, Sunil , Cabantchik, Ioav , Collins, Alan J. , Coyne, Daniel W. , Francisco, Ángel L.M. de , Fishbane, Steven , Gaillard, Carlo A.J.M. , Ganz, Tomas , Goldsmith, David J. , Hershko, Chaim , Jankowska, Ewa A. , Johansen, Kirsten L. , Kalantar-Zadeh, Kamyar , Kalra, Philip A. , Kasiske, Bertram L. , Locatelli, Francesco , Małyszko, Jolanta , Mayer, Gert , McMahon, Lawrence P. , Mikhail, Ashraf , Nemeth, Elizabeta , Barton Pai, Amy , Parfrey, Patrick S. , Pecoits-Filho, Roberto , Roger, Simon D. , Rostoker, Guy , Rottembourg, Jacques , Singh, Ajay K. , Slotki, Itzchak , Spinowitz, Bruce S. , Tarng, Der-Cherng , Tentori, Francesca , Toblli, Jorge E. , Tsukamoto, Yusuke , Vaziri, Nosratola D. , Winkelmayer, Wolfgang C. , Wheeler, David C. , Zakharova, Elena

Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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Chronic Kidney Disease in Children Aged 6–15 Years and Associated Risk Factors in Apizaco, Tlaxcala, Mexico, a Pilot Study

2019 , Ortega-Romero, Manolo , Méndez-Hernández, Pablo , Cruz-Angulo, María del Carmen , Hernández-Sánchez, Ana María , Álvarez-Elías, Ana Catalina , Muñoz-Arizpe, Ricardo , Sales-Heredia, Francisco , Aguilar-Madrid, Guadalupe , Juárez-Perez, Cuauhtémoc Arturo , Soto, Virgilia , Valadés, Teresa , Olvera-Rivas, Nadia , Obrador, Gregorio , Barbier, Olivier C. , Medeiros, Mara

Introduction: Tlaxcala, a small state in central Mexico, has the highest prevalence of chronic kidney disease (CKD) deaths in population aged 5-14 in Mexico, most of them with unknown etiology. Objective: To determine the prevalence of CKD in apparently healthy pediatric population in Apizaco, Tlaxcala. Methods: A cross-sectional pilot study was carried out in children deemed as healthy; subjects with previous diagnosis of CKD were excluded. Informed consent was obtained in all cases. A physical examination was performed, a questionnaire was applied. Blood and urine samples were obtained for serum creatinine, urinalysis, and microalbumin/creatinine ratio. A second and third evaluation was performed after 6 and 18 months in those found with urinary anomalies/CKD to confirm the diagnosis. Results: One hundred and nine subjects completed physical examination, which are the biological samples. Median age was 12 years. CKD stage 2 was confirmed in 5 subjects in the sixth month confirmation visit (4.6%). One patient accepted renal biopsy and Alport Syndrome was found. In a robust multivariate analysis, the risk factors related to reduction in the glomerular filtration rate were males -5.15 mL/min/1.73 m2 (p = 0.002), older participants as by -1.58 mL/min/1.73 m2 per year (p < 0.0001), and among participants living close to a river -3.76 mL/min/1.73 m2 (p = 0.033). Discussion/Conclusion: The prevalence of CKD in the population studied in Apizaco Tlaxcala was confirmed in 4.6 cases per 100 inhabitants between 6 and 15 years. Males, older age, and living close to a river were the risk predictive factors. More studies are needed to determine the causes of the high CKD prevalence in this population. ©2019 S. Karger AG, Basel.

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The ASCEND-NHQ randomized trial found positive effects of daprodustat on hemoglobin and quality of life in patients with non-dialysis chronic kidney disease

2023 , Johansen, Kirsten L. , Cobitz, Alexander R. , Singh, Ajay K. , Macdougall, Iain C. , Lopes, Renato D. , Obrador, Gregorio , Kovesdy, Csaba P. , Israni, Rubeen , Jha, Vivekanand , Okoro, Tony , Sprys, Mike , Jolly, Shivinder , Lindsay, Alistair C. , Bhatt, Purav , Refoios Camejo, Rodrigo , Keeley, Tom , Cizman, Borut , Wheeler, David C.

The ASCEND-NHQ trial evaluated the effects of daprodustat on hemoglobin and the Medical Outcomes Study 36-item Short Form Survey (SF-36) Vitality score (fatigue) in a multicenter, randomized, double-blind, placebo-controlled trial. Adults with chronic kidney disease (CKD) stages 3-5, hemoglobin 8.5-10.0 g/dl, transferrin saturation 15% or more, and ferritin 50 ng/ml or more without recent erythropoiesis-stimulating agent use were randomized (1:1) to oral daprodustat or placebo to achieve and maintain target hemoglobin of 11-12 g/dl over 28 weeks. The primary endpoint was the mean change in hemoglobin between baseline and the evaluation period (Weeks 24-28). Principal secondary endpoints were proportion of participants with a 1 g/dl or more increase in hemoglobin and mean change in the Vitality score between baseline and Week 28. Outcome superiority was tested (1-sided alpha level of 0.025). Overall, 614 participants with non-dialysis-dependent CKD were randomized. The adjusted mean change in hemoglobin from baseline to the evaluation period was greater with daprodustat (1.58 vs 0.19 g/dl). The adjusted mean treatment difference (AMD) was significant at 1.40 g/dl (95% confidence interval 1.23, 1.56). A significantly greater proportion of participants receiving daprodustat showed a 1 g/dl or greater increase in hemoglobin from baseline (77% vs 18%). The mean SF-36 Vitality score increased by 7.3 and 1.9 points with daprodustat and placebo, respectively; a clinically and statistically significant 5.4 point Week 28 AMD increase. Adverse event rates were similar (69% vs 71%); relative risk 0.98, (95% confidence interval 0.88, 1.09). Thus, in participants with CKD stages 3-5, daprodustat resulted in a significant increase in hemoglobin and improvement in fatigue without an increase in the overall frequency of adverse events. Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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The ASCEND-ND trial: study design and participant characteristics

2021 , Perkovic, Vlado , Blackorby, Allison , Cizman, Borut , Carroll, Kevin , Cobitz, Alexander R. , Davies, Rich , DiMino, Tara L. , Jha, Vivekanand , Johansen, Kirsten L. , Lopes, Renato D. , Kler, Lata , Macdougall, Iain C. , McMurray, John J. V. , Meadowcroft, Amy M. , Obrador, Gregorio , Solomon, Scott , Taft, Lin , Wanner, Christoph , Waikar, Sushrut S. , Wheeler, David C. , Wiecek, Andrzej , Singh, Ajay K.

Background: Anaemia is common in chronic kidney disease (CKD) and assessment of the risks and benefits of new therapies is important. Methods: The Anaemia Study in CKD: Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Non-Dialysis (ASCEND-ND) trial includes adult patients with CKD Stages 3-5, not using erythropoiesis-stimulating agents (ESAs) with screening haemoglobin (Hb) 8-10 g/dL or receiving ESAs with screening Hb of 8-12 g/dL. Participants were randomized to daprodustat or darbepoetin alfa (1:1) in an open-label trial (steering committee- and sponsor-blinded), with blinded endpoint assessment. The co-primary endpoints are mean change in Hb between baseline and evaluation period (average over Weeks 28-52) and time to first adjudicated major adverse cardiovascular (CV) event. Baseline characteristics were compared with those of participants in similar anaemia trials. © The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.

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Genetic and environmental risk factors for chronic kidney disease

2017 , Obrador, Gregorio , Schultheiss, Ulla T. , Kretzler, Matthias , Langham, Robyn G. , Nangaku, Masaomi , Pecoits-Filho, Roberto , Pollock, Carol , Rossert, Jerome , Correa-Rotter, Ricardo , Stenvinkel, Peter , Walker, Robert , Yang, Chih-Wei , Fox, Caroline S. , Köttgen, Anna

In order to change the current state of chronic kidney disease knowledge and therapeutics, a fundamental improvement in the understanding of genetic and environmental causes of chronic kidney disease is essential. This article first provides an overview of the existing knowledge gaps in our understanding of the genetic and environmental causes of chronic kidney disease, as well as their interactions. The second part of the article formulates goals that should be achieved in order to close these gaps, along with suggested timelines and stakeholders that are to be involved. A better understanding of genetic and environmental factors and their interactions that influence kidney function in healthy and diseased conditions can provide novel insights into renal physiology and pathophysiology and result in the identification of novel therapeutic or preventive targets to tackle the global public health care problem of chronic kidney disease. © Kidney International Supplements.

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Longitudinal Analysis of Participants in The KEEP Mexico's Chronic Kidney Disease Screening Program

2013 , Obrador, Gregorio , Olvera, Nadia , Gutiérrez, Verónica , Contreras, Daniela , Reyes, Rebeca , Villa Romero, Antonio Rafael

Background and aims: The Kidney Early Evaluation Program (KEEP) is a free screening and educational program aimed at detecting chronic kidney disease (CKD) among adult individuals who are at high-risk (those with diabetes, hypertension, or family history of these conditions or CKD). Confirmation of CKD diagnosis requires persistence of albuminuria or estimated GFR <60 mL/min for at least 3 months. We undertook this study to determine in a follow-up KEEP done at least 1 year after a baseline KEEP the following: 1) CKD incidence among individuals who initially tested negative for CKD, 2) transitions between CKD stages among individuals who initially tested positive for CKD. Methods: A random sample of KEEP participants was invited to participate in a follow-up KEEP between 2008 and 2010. Paired analyses were conducted to compare CKD stages between baseline and follow-up KEEP. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

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Executive summary of the KDIGO Controversies Conference on Supportive Care in Chronic Kidney Disease: developing a roadmap to improving quality care

2015 , Davison, Sara N. , Levin, Adeera , Moss, Alvin H. , Jha, Vivekanand , Brown, Edwina A. , Brennan, Frank , Murtagh, Fliss E.M. , Naicker, Saraladevi , Germain, Michael J. , O'Donoghue, Donal J. , Morton, Rachael L. , Obrador, Gregorio

Patients with advanced chronic kidney disease (CKD) have a high burden of physical and psychosocial symptoms, poor outcomes, and high costs of care. Current paradigms of care for this highly vulnerable population are variable, prognostic and assessment tools are limited, and quality of care, particularly regarding conservative and palliative care, is suboptimal. The KDIGO Controversies Conference on Supportive Care in CKD reviewed the current state of knowledge in order to define a roadmap to guide clinical and research activities focused on improving the outcomes of people living with advanced CKD, including those on dialysis. An international group of multidisciplinary experts in CKD, palliative care, methodology, economics, and education identified the key issues related to palliative care in this population. The conference led to a working plan to address outstanding issues in this arena, and this executive summary serves as an output to guide future work, including the development of globally applicable. Copyright © Elsevier B.V., its licensors, and contributors