TY - JOUR
T1 - Euglycemic ketoacidosis as a complication of sglt2 inhibitor therapy
AU - Palmer, Biff F.
AU - Clegg, Deborah J.
N1 - Publisher Copyright:
© 2021 by the American Society of Nephrology.
PY - 2021/8
Y1 - 2021/8
N2 - Sodium-glucose cotransporter-2 (SGLT2) inhibitors are drugs designed tolower plasma glucose concentrationby inhibiting Na1-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 Na1 or K1 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.
AB - Sodium-glucose cotransporter-2 (SGLT2) inhibitors are drugs designed tolower plasma glucose concentrationby inhibiting Na1-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 Na1 or K1 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.
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U2 - 10.2215/CJN.17621120
DO - 10.2215/CJN.17621120
M3 - Review article
C2 - 33563658
AN - SCOPUS:85111595566
SN - 1555-9041
VL - 16
SP - 1284
EP - 1291
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 8
ER -