Obrador, Gregorio
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Preferred name
Obrador, Gregorio
Official Name
Tomás Obrador Vera, Gregorio
Alternative Name
gobrador
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ORCID
Scopus Author ID
6602806471
Researcher ID
B-3054-2011

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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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Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis

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

Background: Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHIs) are as effective as erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels. Methods: In this randomized, open-label, phase 3 trial, we assigned patients with CKD who were undergoing dialysis and who had a hemoglobin level of 8.0 to 11.5 g per deciliter to receive an oral HIF-PHI (daprodustat) or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). The two primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 (noninferiority margin, −0.75 g per deciliter) and the first occurrence of a major adverse cardiovascular event (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), with a noninferiority margin of 1.25. Copyright © Massachusetts Medical Society.

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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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Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis

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

Background: Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. In patients with chronic kidney disease (CKD) who are not undergoing dialysis, the efficacy and safety of daprodustat, as compared with the conventional erythropoiesis-stimulating agent darbepoetin alfa, are unknown. Methods: In this randomized, open-label, phase 3 trial with blinded adjudication of cardiovascular outcomes, we compared daprodustat with darbepoetin alfa for the treatment of anemia in patients with CKD who were not undergoing dialysis. The primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 and the first occurrence of a major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke). Copyright © 2021 Massachusetts Medical Society.

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Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy

2017 , Levin, Adeera , Tonelli, Marcello , Bonventre, Joseph , Coresh, Josef , Donner, Jo-Ann , Fogo, Agnes B. , Fox, Caroline S. , Gansevoort, Ron T. , Heerspink, Hiddo J.L. , Jardine, Meg , Kasiske, Bertram , Köttgen, Anna , Kretzler, Matthias , Levey, Andrew S. , Luyckx, Valerie A. , Mehta, Ravindra , Moe, Orson , Obrador, Gregorio , Pannu, Neesh , Parikh, Chirag R. , Perkovic, Vlado , Pollock, Carol , Stenvinkel, Peter , Tuttle, Katherine R. , Wheeler, David C. , Eckardt, Kai-uwe

The global nephrology community recognises the need for a cohesive plan to address the problem of chronic kidney disease (CKD). In July, 2016, the International Society of Nephrology hosted a CKD summit of more than 85 people with diverse expertise and professional backgrounds from around the globe. The purpose was to identify and prioritise key activities for the next 5–10 years in the domains of clinical care, research, and advocacy and to create an action plan and performance framework based on ten themes: strengthen CKD surveillance; tackle major risk factors for CKD; reduce acute kidney injury—a special risk factor for CKD; enhance understanding of the genetic causes of CKD; establish better diagnostic methods in CKD; improve understanding of the natural course of CKD; assess and implement established treatment options in patients with CKD; improve management of symptoms and complications of CKD; develop novel therapeutic interventions to slow CKD progression and reduce CKD complications; and increase the quantity and quality of clinical trials in CKD. Each group produced a prioritised list of goals, activities, and a set of key deliverable objectives for each of the themes. The intended users of this action plan are clinicians, patients, scientists, industry partners, governments, and advocacy organisations. Implementation of this integrated comprehensive plan will benefit people who are at risk for or affected by CKD worldwide. © The Lancet

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Study design and baseline characteristics of patients on dialysis in the ASCEND-D trial

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

Background: The Anemia Studies in chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Dialysis (ASCEND-D) trial will test the hypothesis that daprodustat is noninferior to comparator epoetin alfa or darbepoetin alfa for two co-primary endpoints: hemoglobin (Hb) efficacy and cardiovascular (CV) safety. Methods: We report the trial design, key demographic, clinical and laboratory findings, and baseline therapies of 2964 patients randomized in the open-label (sponsor-blinded) active-controlled, parallel-group, randomized ASCEND-D clinical trial. We also compare baseline characteristics of ASCEND-D patients with patients who are on dialysis (CKD G5D) enrolled in other large CV outcome trials (CVOTs) and in the most relevant registries. © The Author(s) 2021. Published by Oxford University Press on behalf of the ERA-EDTA.

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Efficacy and Safety of Daprodustat for Treatment of Anemia of Chronic Kidney Disease in Incident Dialysis Patients

2022 , Singh, Ajay K. , Cizman, Borut , Carroll, Kevin , McMurray, John J. V. , Perkovic, Vlado , Vivekanand, Jha , Johansen, Kirsten L. , Lopes, Renato D. , Macdougall, Iain C. , Obrador, Gregorio , Waikar, Sushrut S. , Wanner, Christoph , Wheeler, David C. , Wiecek, Andrzej , Stankus, Nicole , Strutz, Frank , Blackorby, Allison , Cobitz, Alexander R. , Meadowcroft, Amy M. , Paul, Gitanjali , Ranganathan, Prerna , Sedani, Sangeeta , Solomon, Scott

Importance: Daprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated as an oral alternative to conventional erythropoiesis-stimulating agent (ESA) therapy. Few studies of anemia treatment in an incident dialysis (ID) population have been reported. Objective: To evaluate the efficacy and safety of daprodustat vs darbepoetin alfa in treating anemia of chronic kidney disease in ID patients. Design, setting, and participants: This prospective, randomized, open-label clinical trial was conducted from May 11, 2017, through September 24, 2020, in 90 centers across 14 countries. Patients with advanced CKD were eligible if they planned to start dialysis within 6 weeks from screening or had started and received hemodialysis (HD) or peritoneal dialysis (PD) within 90 days before randomization, had a screening hemoglobin (Hb) concentration of 8.0 to 10.5 g/dL (to convert to grams per liter, multiply by 10) and a randomization Hb of 8.0 to 11.0 g/dL, were ESA-naive or had received limited ESA treatment, and were iron-replete. Interventions: Randomized 1:1 to daprodustat or darbepoetin alfa. Main outcomes and measures: The primary analysis in the intent-to-treat population evaluated the mean change in Hb concentration from baseline to evaluation period (weeks 28-52) to assess noninferiority of daprodustat vs darbepoetin alfa (noninferiority margin, -0.75 g/dL). The mean monthly intravenous (IV) iron dose from baseline to week 52 was the principal secondary end point. Rates of treatment-emergent and serious adverse events (AEs) were also compared between treatment groups to assess safety and tolerability. Results: A total of 312 patients (median [IQR] age, 55 [45-65] years; 194 [62%] male) were randomized to either daprodustat (157 patients; median [IQR] age, 52.0 [45-63] years; 96 [61%] male) or darbepoetin alfa (155 patients; median [IQR] age, 56.0 [45-67] years; 98 [63%] male); 306 patients (98%) completed the trial. The mean (SD) Hb concentration during the evaluation period was 10.5 (1.0) g/dL for the daprodustat and 10.6 (0.9) g/dL for the darbepoetin alfa group, with an adjusted mean treatment difference of -0.10 g/dL (95% CI, -0.34 to 0.14 g/dL), indicating noninferiority. There was a reduction in mean monthly IV iron use from baseline to week 52 in both treatment groups; however, daprodustat was not superior compared with darbepoetin alfa in reducing monthly IV iron use (adjusted mean treatment difference, 19.4 mg [95% CI, -11.0 to 49.9 mg]). Adverse event rates were 76% for daprodustat vs 72% for darbepoetin alfa.

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Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

2020 , Clase, Catherine M. , Carrero, Juan-Jesús , Ellison, David H. , Grams, Morgan E. , Hemmelgarn, Brenda R. , Jardine, Meg J. , Kovesdy, Csaba P. , Kline, Gregory A. , Lindner, Gregor , Obrador, Gregorio , Palmer, Biff F. , Cheung, Michael , Wheeler, David C. , Winkelmayer, Wolfgang C. , Pecoits-Filho, Roberto , Ashuntantang, Gloria E. , Bakker, Stephan J.L. , Bakris, George L. , Bhandari, Sunil , Burdmann, Emmanuel A. , Campbell, Katrina L. , Charytan, David M. , Clegg, Deborah J. , Cuppari, Lilian , Goldsmith, David , Hallan, Stein I. , He, Jiang , Herzog, Charles A. , Hoenig, Melanie P. , Hoorn, Ewout J. , Leipziger, Jens Georg , Leonberg-Yoo, Amanda K. , Lerma, Edgar V. , López-Almaraz, José Ernesto , Małyszko, Jolanta , Mann, Johannes F.E. , Marklund, Matti , McDonough, Alicia A. , Nagahama, Masahiko , Navaneethan, Sankar D. , Pitt, Bertram , Pochynyuk, Oleh M. , Proença de Moraes, Thyago , Rafique, Zubaid , Robinson, Bruce M. , Roger, Simon D. , Rossignol, Patrick , Singer, Adam J. , Smyth, Andrew , Sood, Manish M. , Walsh, Michael , Weir, Matthew R. , Wingo, Charles S.

Potassium disorders are common in patients with kidney disease, particularly in patients with tubular disorders and low glomerular filtration rate. A multidisciplinary group of researchers and clinicians met in October 2018 to identify evidence and address controversies in potassium management. The issues discussed encompassed our latest understanding of the regulation of tubular potassium excretion in health and disease; the relationship of potassium intake to cardiovascular and kidney outcomes, with increasing evidence showing beneficial associations with plant-based diet and data to suggest a paradigm shift from the idea of dietary restriction toward fostering patterns of eating that are associated with better outcomes; the paucity of data on the effect of dietary modification in restoring abnormal serum potassium to the normal range; a novel diagnostic algorithm for hypokalemia that takes into account the ascendency of the clinical context in determining cause, aligning the educational strategy with a practical approach to diagnosis; and therapeutic approaches in managing hyperkalemia when chronic and in the emergency or hospital ward. In sum, we provide here our conference deliberations on potassium homeostasis in health and disease, guidance for evaluation and management of dyskalemias in the context of kidney diseases, and research priorities in each of the above areas. Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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