Altered Prostaglandin Signaling as a Cause of Thiazide-Induced Hyponatremia  Biff F. Palmer, Deborah J. Clegg  American Journal of Kidney Diseases  Volume 71, Issue 6, Pages 769-771 (June 2018) DOI: 10.1053/j.ajkd.2017.11.026 Copyright © 2018 National Kidney Foundation, Inc. Terms and Conditions

Figure 1 Under normal conditions, the hydro-osmotic effect of increased arginine vasopressin (AVP) is counterbalanced by increased renal prostaglandin E2 (PGE2) production. PGE2 is directed to the basolateral side of the collecting duct by the prostaglandin transporter encoded by SLCO2A1 (PGT) to facilitate signaling through prostaglandin receptors 1 (EP1) and 3 (EP3), causing retrieval of aquaporin 2 (AP2) from the apical membrane. Administration of a thiazide diuretic in some patients with the SLCO2A1 variant leads to increased PGE2 concentrations in the tubular lumen. Increased PGE2/EP4 signaling leads to insertion of AP2 water channels into the apical membrane and results in increased water reabsorption in an AVP-independent manner. The signal for increased PGE2 production in this setting is unclear. American Journal of Kidney Diseases 2018 71, 769-771DOI: (10.1053/j.ajkd.2017.11.026) Copyright © 2018 National Kidney Foundation, Inc. Terms and Conditions