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Browsing by Author "Massy, Ziad A."
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Item Cardiovascular complications in chronic kidney disease: a review from the European Renal and Cardiovascular Medicine Working Group of the European Renal Association(Oxford University Press, 2023) Zoccali, Carmine; Mallamaci, Francesca; Adamczak, Marcin; Bueno de Oliveira, Rodrigo; Massy, Ziad A.; Sarafidis, Pantelis; Agarwal, Rajiv; Mark, Patrick B.; Kotanko, Peter; Ferro, Charles J.; Wanner, Christoph; Burnier, Michel; Vanholder, Raymond; Wiecek, Andrzej; Medicine, School of MedicineChronic kidney disease (CKD) is classified into five stages with kidney failure being the most severe stage (stage G5). CKD conveys a high risk for coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. Cardiovascular complications are the most common causes of death in patients with kidney failure (stage G5) who are maintained on regular dialysis treatment. Because of the high death rate attributable to cardiovascular (CV) disease, most patients with progressive CKD die before reaching kidney failure. Classical risk factors implicated in CV disease are involved in the early stages of CKD. In intermediate and late stages, non-traditional risk factors, including iso-osmotic and non-osmotic sodium retention, volume expansion, anaemia, inflammation, malnutrition, sympathetic overactivity, mineral bone disorders, accumulation of a class of endogenous compounds called 'uremic toxins', and a variety of hormonal disorders are the main factors that accelerate the progression of CV disease in these patients. Arterial disease in CKD patients is characterized by an almost unique propensity to calcification and vascular stiffness. Left ventricular hypertrophy, a major risk factor for heart failure, occurs early in CKD and reaches a prevalence of 70-80% in patients with kidney failure. Recent clinical trials have shown the potential benefits of hypoxia-inducible factor prolyl hydroxylase inhibitors, especially as an oral agent in CKD patients. Likewise, the value of proactively administered intravenous iron for safely treating anaemia in dialysis patients has been shown. Sodium/glucose cotransporter-2 inhibitors are now fully emerged as a class of drugs that substantially reduces the risk for CV complications in patients who are already being treated with adequate doses of inhibitors of the renin-angiotensin system. Concerted efforts are being made by major scientific societies to advance basic and clinical research on CV disease in patients with CKD, a research area that remains insufficiently explored.Item Cardiovascular outcome trials in patients with chronic kidney disease: challenges associated with selection of patients and endpoints(Oxford Academic, 2019-03-14) Rossignol, Patrick; Agarwal, Rajiv; Canaud, Bernard; Charney, Alan; Chatellier, Gilles; Craig, Jonathan C.; Cushman, William C.; Gansevoort, Ronald T.; Fellström, Bengt; Garza, Dahlia; Guzman, Nicolas; Holtkamp, Frank A.; London, Gerard M.; Massy, Ziad A.; Mebazaa, Alexandre; Mol, Peter G.M.; Pfeffer, Marc A.; Rosenberg, Yves; Ruilope, Luis M.; Seltzer, Jonathan; Shah, Amil M.; Shah, Salim; Singh, Bhupinder; Stefánsson, Bergur V.; Stockbridge, Norman; Gattis Stough, Wendy; Thygesen, Kristian; Walsh, Michael; Wanner, Christoph; Warnock, David G.; Wilcox, Christopher S.; Wittes, Janet; Pitt, Bertram; Thompson, Aliza; Zannad, Faiez; Medicine, School of MedicineAlthough cardiovascular disease is a major health burden for patients with chronic kidney disease, most cardiovascular outcome trials have excluded patients with advanced chronic kidney disease. Moreover, the major cardiovascular outcome trials that have been conducted in patients with end-stage renal disease have not demonstrated a treatment benefit. Thus, clinicians have limited evidence to guide the management of cardiovascular disease in patients with chronic kidney disease, particularly those on dialysis. Several factors contribute to both the paucity of trials and the apparent lack of observed treatment effect in completed studies. Challenges associated with conducting trials in this population include patient heterogeneity, complexity of renal pathophysiology and its interaction with cardiovascular disease, and competing risks for death. The Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT), an international organization of academic cardiovascular and renal clinical trialists, held a meeting of regulators and experts in nephrology, cardiology, and clinical trial methodology. The group identified several research priorities, summarized in this paper, that should be pursued to advance the field towards achieving improved cardiovascular outcomes for these patients. Cardiovascular and renal clinical trialists must partner to address the uncertainties in the field through collaborative research and design clinical trials that reflect the specific needs of the chronic and end-stage kidney disease populations, with the shared goal of generating robust evidence to guide the management of cardiovascular disease in patients with kidney disease.