Abstract: TH-PO407
Urinary Prostaglandin E2 Excretion Is Associated With Disease Progression in Polycystic Kidney Disease
Session Information
- Genetic Diseases of the Kidneys: Cystic - I
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1101 Genetic Diseases of the Kidneys: Cystic
Authors
- Geurts, Frank, Erasmus MC, Rotterdam, Netherlands
- Messchendorp, A. Lianne, University Medical Center Groningen, Groningen, Netherlands
- Gansevoort, Ron T., University Medical Center Groningen, Groningen, Netherlands
- Meijer, Esther, University Medical Center Groningen, Groningen, Netherlands
- Zietse, Robert, Erasmus MC, Rotterdam, Netherlands
- Salih, Mahdi, Erasmus MC, Rotterdam, Netherlands
- Fenton, Robert A., Aarhus Universitet, Aarhus, Midtjylland, Denmark
- Hoorn, Ewout J., Erasmus MC, Rotterdam, Netherlands
Background
In cell and animal models of autosomal dominant polycystic kidney disease (ADPKD) cyst growth is enhanced by prostaglandin E2 (PGE2). Here, we hypothesize that higher urinary PGE2 excretion in patients with ADPKD is associated with faster disease progression.
Methods
We used samples from the DIPAK study, a prospective multi-center cohort of patients with ADPKD, and measured 24h urine PGE2 and its metabolites (PGEM). Linear mixed models were used to analyze the association of PGE excretion with disease progression assessed by eGFR slope. The relation between urinary PGE excretion and a composite outcome of 40% loss of eGFR or kidney failure was analyzed using Cox regression models. PGE excretions were log transformed prior to analysis.
Results
Urinary PGE2 and PGEM excretion was measured in 590 patients (48±12 years, eGFR 73±28 ml/min/1.73m2) and independently associated with height adjusted total kidney volume (htTKV, β 0.10 p=0.04). A total of 504 patients were available for the eGFR slope and survival analysis (median of 4.2 eGFR measurements and 3.1 years of follow-up). The mean eGFR slope in the linear mixed model was -2.9 ml/min/1.73m2/year. A higher urinary excretion of PGE2 and PGEM were both significantly associated with faster eGFR decline. When correcting for htTKV, this effect persisted for PGEM (Table). Higher urinary PGE2 (HR 2.02 p=0.02) and PGEM (HR 3.65 p=0.008) excretion was associated with a higher incidence of kidney failure or 40% loss of eGFR after correcting for baseline characteristics, but this effect lost statistical significance after correction for htTKV (PGE2: HR 1.75 p=0.12, PGEM: HR 2.51 p=0.051).
Conclusion
Higher urinary PGE2 and PGEM excretion is associated with faster eGFR decline in ADPKD. The relation of PGE2 with htTKV suggests cyst-related production. Our findings suggest that in patients with ADPKD, PGE2 and PGEM should be further investigated as markers of disease progression or even as potential therapeutic targets.
Table 1: Linear mixed model of urinary PGE and PGEM excretion with eGFR slope.
| Model 1 | Model 2 | Model 3 | ||||
| variables | β | p-value | β | p-value | β | p-value |
| PGE2 ng/24h | -1.2 | 0.001 | -1.2 | 0.002 | -0.24 | 0.5 |
| PGEM ng/24h | -1.9 | <0.001 | -1.5 | 0.004 | -1.11 | 0.03 |
model1: unadjusted, model2: adjusted for age, sex BMI, albuminuria and PKD mutation, model3: model2+hTKV