Abstract: PO1454
Extracellular Volume and Plasma Potassium Determine Urinary Prostaglandin E2 Excretion in Kidney Disease
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Clinical - 1
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolyte, and Acid-Base Disorders
- 902 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Geurts, Frank, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
- Bovee, Dominique M., Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
- Gritter, Martin, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
- van Bommel, Erik J. M., Amsterdam Universitair Medische Centra, Amsterdam, Noord-Holland, Netherlands
- Cuevas, Catherina A., Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
- van Raalte, Daniël H., Amsterdam Universitair Medische Centra, Amsterdam, Noord-Holland, Netherlands
- Fenton, Robert A., Aarhus Universitet, Aarhus, Denmark
- Hoorn, Ewout J., Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
Background
Prostaglandin E2 (PGE2) is the most abundantly produced prostaglandin in the kidney where it plays a key role in renin secretion and electrolyte handling. It is unknown whether urinary PGE2 excretion is a reflection of these functions in patients with kidney disease. Here, our aims were to (1) analyze the changes in urinary PGE2 excretion during interventions modulating extracellular volume (ECV) or electrolyte homeostasis and (2) identify the determinants of urinary PGE2 excretion.
Methods
Urinary PGE2 and PGE2 metabolite (PGEM) excretions were measured in two studies in chronic kidney disease patients: 1) a randomized cross-over trial comparing a low sodium (Na+) diet (60 mmol/day) with amiloride/hydrochlorothiazide (n=26, each intervention 2 weeks), 2) a 2-week intervention with potassium chloride supplementation (40 mmol day, n=28), and in patients with diabetic kidney disease from a 12-week randomized trial comparing dapagliflozin (n=23) with gliclazide (n=19). The baseline data of these studies were combined (n=96) to identify determinants of urinary PGE2 using multivariable linear regression with correction for age, sex, eGFR, and study.
Results
A low Na+ diet, amiloride/hydrochlorothiazide, and dapagliflozin reduced ECV and increased plasma renin. Amiloride/hydrochlorothiazide and dapagliflozin increased total urinary PGE2 excretion by 5.3% (95% CI 1.9-8.7%) and 5.8% (95% CI 0.9-10.8%), respectively, while a low Na+ diet increased PGEM excretion by 5.9% (95% CI 1.2-10.6%). Potassium supplementation had no effect on ECV, plasma renin, or urinary PGE2 excretion. On multivariable linear regression total urinary PGE2 excretion was associated with plasma renin (β 0.3, 95% CI 0.2-0.4), urinary Na+ excretion (β 0.003, 95% CI 0.0007-0.006), and plasma potassium (β 0.7, 95% CI 0.3-1.0).
Conclusion
Interventions that decrease extracellular volume increase urinary PGE2 excretion. In addition, plasma renin, urinary Na+ excretion, and plasma potassium are independently associated with urinary PGE2 excretion. Our data suggest that in patients with kidney disease urinary PGE2 excretion not only reflects the kidney’s response to changes in extracellular volume but also plasma potassium.
Funding
- Private Foundation Support