Complications of metabolic acidosis and alkalinizing therapy in chronic kidney disease patients: a clinician-directed or
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		    NEPHROLOGY - REVIEW
 
 Complications of metabolic acidosis and alkalinizing therapy in chronic kidney disease patients: a clinician‑directed organ‑specific primer Sidar Copur1 · Alan A. Sag2 · Baris Afsar3 · Patrick Rossignol4 · Adrian Covic5 · Mehmet Kanbay6  Received: 19 May 2020 / Accepted: 29 June 2020 © Springer Nature B.V. 2020
 
 Abstract Chronic kidney disease is prevalent, affecting more than one in ten adults. In this population, metabolic acidosis is considered a key underlying pathophysiological feature, tying together bone mineral disorders, sarcopenia, insulin resistance, vascular calcification, pro-inflammatory and pro-thrombotic states. This review aims to address the paucity of literature on alkalinizing agents, a promising treatment option that has known adverse effects. Keywords  Chronic kidney disease · End-stage renal disease · Metabolic acidosis · Alkaline treatment · Bicarbonate
 
 Introduction Chronic kidney disease (CKD) is a global health problem affecting more than 1 in 10 people, disproportionately those in low to middle income countries compared with high income countries [1–4]. CKD causes metabolic acidosis which leads to cardiovascular events, vascular complications, insulin resistance, endothelial dysfunction, sarcopenia, bone mineral disorders, vascular calcification, and inflammation [5, 6]. However, the exact mechanism of each of these seemingly disparate complications is nuanced and
 
 affects treatment. Although recent studies and reviews suggest that oral alkali supplementation or a reduction in dietary acid intake may slow the rate of kidney function decline and potentially reduce the risk of end-stage kidney disease in patients with CKD and metabolic acidosis [7, 8], none of the recent reviews discussed the other systemic adverse effect of metabolic acidosis and effect of alkaline treatment (Fig. 1). Therefore, we aimed to provide a clinician-directed primer of CKD complications from the vantage point of metabolic acidosis and alkalinizing therapies, with implications regarding treatment for each of these.
 
 * Mehmet Kanbay [email protected]; [email protected]
 
 Metabolic acidosis and vascular defects
 
 1
 
 
 
 Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
 
 Endothelial dysfunction
 
 2
 
 
 
 Division of Vascular and Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, USA
 
 3
 
 Division of Nephrology, Department of Internal Medicine, Suleyman Demirel University School of Medicine, Isparta, Turkey
 
 4
 
 Université de Lorraine, INSERM CIC-P 1433, CHRU de Nancy, INSERM U1116, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France
 
 5
 
 Department of Nephrology, Grigore T. Popa’ University of Medicine, Iasi, Romania
 
 6
 
 Department of Medicine, Division of Nephrology, Koc University School of Medicine, 34010 Istanbul, Turkey
 
 CKD-induced metabolic acidosis vasodilates large arteries while vasoconstricting small arteries. Hypercapnic acidosis does this via regulation of nitric oxide (NO) production, calcium channels		
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