Abstract: TH-PO1023
Effect of Pregnancy on Kidney Lifespan in Alport Nephropathy: Triple Therapy Offers Limited Protection
Session Information
- Women's Health and Kidney Diseases
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Women's Health and Kidney Diseases
- 2200 Women's Health and Kidney Diseases
Authors
- Chang, Liang, Ludwig-Maximilians-Universitat Munchen, Munich, BY, Germany
- Wang, Zetao, Harbin Medical University, Harbin, Heilongjiang, China
- Yang, Huan, Ludwig-Maximilians-Universitat Munchen, Munich, BY, Germany
- Abinti, Matteo, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Anders, Hans J., Ludwig-Maximilians-Universitat Munchen, Munich, BY, Germany
Background
Pregnancy exacerbates kidney workload, elevating risks of preeclampsia, kidney function loss, and poor fetal outcomes in women with chronic kidney disease (CKD). Current research often focuses on short-term markers like eGFR and proteinuria, neglecting long-term kidney events. This study investigates kidney lifespan in pregnant CKD subjects, with and without renin-angiotensin system (RAS), sodium-glucose transporter-2 (SGLT-2), and mineralocorticoid receptor (MR) inhibitors, using a preclinical CKD model.
Methods
Female Col4a3-deficient mice with established Alport nephropathy were randomized into four groups: 1) vehicle only (nil), 2) late treatment starting at 6 weeks of age, 3) early treatment starting at 3 weeks of age, and 4) early treatment with one pregnancy, all with food admixtures of ramipril (10 mg/kg), empagliflozin (30 mg/kg), and finerenone (10 mg/kg). During pregnancy, only dual therapy with empagliflozin and finerenone was administered post-mating. Full triple therapy was given post-delivery.
Results
Mean survival time of non-pregnant and untreated Alport nephropathy mice up to the uremic stage of CKD was 62.90±7.340 days (vehicle). Late onset of triple therapy prolonged survival time to 97.70±23.68 days (late), early onset of triple therapy to 137.6±27.15 days (early), respectively. With in intercurrent pregnancy, survival time was reduced to 96.50±19.71 days despite an early onset of therapy, respectively (Figure A). While all groups showed late-stage weight loss, the pregnancy group exhibited a more pronounced decline postpartum, suggesting an accelerated health decline after pregnancy (Figure B).
Conclusion
Early triple therapy for CKD significantly improves kidney survival, even enabling pregnancy in otherwise non-viable subjects. However, pregnancy diminishes the therapy's renoprotective effect, likely by increasing kidney workload and accelerating kidney decline. These findings highlight the long-term benefits of triple therapy and the impact of pregnancy on diseased kidneys, underscoring the need for careful counseling of women with CKD.
Figure