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Euglycemic Ketoacidosis as a Complication of SGLT2 Inhibitor Therapy

Biff F. Palmer and Deborah J. Clegg
CJASN February 2021, CJN.17621120; DOI: https://doi.org/10.2215/CJN.17621120
Biff F. Palmer
1Division of Nephrology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
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Deborah J. Clegg
2Associate Dean for Research, College of Nursing and Health Professionals, Drexel University, Philadelphia, Pennsylvania
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Abstract

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are drugs designed to lower plasma glucose concentration by inhibiting Na+-glucose–coupled transport in the proximal tubule. Clinical trials demonstrate these drugs have favorable effects on cardiovascular outcomes to include slowing the progression of CKD. Although most patients tolerate these drugs, a potential complication is development of ketoacidosis, often with a normal or only a minimally elevated plasma glucose concentration. Inhibition of sodium-glucose cotransporter-2 in the proximal tubule alters kidney ATP turnover so that filtered ketoacids are preferentially excreted as Na+ or K+ salts, leading to indirect loss of bicarbonate from the body and systemic acidosis under conditions of increased ketogenesis. Risk factors include reductions in insulin dose, increased insulin demand, metabolic stress, low carbohydrate intake, women, and latent autoimmune diabetes of adulthood. The lack of hyperglycemia and nonspecific symptoms of ketoacidosis can lead to delays in diagnosis. Treatment strategies and various precautions are discussed that can decrease the likelihood of this complication.

  • euglycemic ketoacidosis
  • sodium glucose co-transporter inhibitor
  • Copyright © 2021 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology: 16 (2)
Clinical Journal of the American Society of Nephrology
Vol. 16, Issue 2
February 08, 2021
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Euglycemic Ketoacidosis as a Complication of SGLT2 Inhibitor Therapy
Biff F. Palmer, Deborah J. Clegg
CJASN Feb 2021, CJN.17621120; DOI: 10.2215/CJN.17621120

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Euglycemic Ketoacidosis as a Complication of SGLT2 Inhibitor Therapy
Biff F. Palmer, Deborah J. Clegg
CJASN Feb 2021, CJN.17621120; DOI: 10.2215/CJN.17621120
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  • Article
    • Abstract
    • Introduction
    • Risk of Ketoacidosis with Sodium-Glucose Cotransporter-2 Inhibitor
    • Increased Ketogenesis with Sodium-Glucose Cotransporter-2 Inhibitor
    • Sodium-Glucose Cotransporter-2 Inhibitor Effects on Kidney Function Predisposing to Ketoacidosis
    • Risk Factors for Development of Ketoacidosis
    • Clinical Features and Treatment of Sodium-Glucose Cotransporter-2 Inhibitor–Induced Ketoacidosis
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More in this TOC Section

  • Management of Heart Failure Patient with CKD
  • Mass Disasters and Burnout in Nephrology Personnel
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