Kidney Week

Abstract: SA-PO0867

Renoprotective Effects of Direct Oral Anticoagulants in Glomerular Diseases

Session Information

• Glomerular Diseases: Management, Evolving Strategies, and Practice-Changing Advances
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Oseguera, Mayra A., Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Mayra A. Oseguera, MD

• Waller, Amanda P., Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Amanda P. Waller, PhD

• Abdelghani, Eman, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Eman Abdelghani, MD

• Wolfgang, Katelyn, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Katelyn Wolfgang

• Muralidharan, Kaushik, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Kaushik Muralidharan, MS, PhD

• Spruill, Brittney, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Brittney Spruill

• Kerlin, Bryce A., Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Bryce A. Kerlin, MD

Background

Progressive podocyte injury and loss initiates a pathological cascade that progressively leads to CKD. We have previously demonstrated that thrombin injures cultured podocytes and that both thrombin antagonism and knockdown ameliorated proteinuria in in vivo models of glomerular disease. We hypothesized that direct oral anticoagulant (DOAC) therapy would ameliorate both acute and chronic glomerular disease and mitigate progression in chronic disease.

Methods

We used the puromycin aminonucleoside (PAN) and podocin-diphtheria toxin receptor (pDTR) rat models of acute (10-day) and chronic (10-week) glomerular disease. Following disease induction rats received daily oral rivaroxaban (riva; 3 mg/kg), dabigatran (dabi; 20 mg/kg), or sham, and were compared to healthy controls (n=4-11/group). DOAC therapy was initiated on day 0 or 5 in the acute and chronic models, respectively. Glomerular filtration rate (GFR) was determined by transdermal FITC-sinistrin clearance in the chronic model. At the end of the experiments, morning spot urines and citrated plasma were collected. Glomeruli were isolated, dissociated into single-cell suspensions and analyzed by flow cytometry.

Results

Dabi and riva effectively reduced proteinuria, podocytopathy, and podocytopenia in both acute models (p<0.05). In the chronic model both DOACs ameliorated proteinuria, podocytopathy, podocytopenia, podocyturia (urinary Nphs2 mRNA), and reduced GFR loss (Figure). Both DOACs also significantly ameliorated proteinuria-associated hypercoagulopathy and in vivo thrombosis.

Conclusion

DOAC therapy may provide a novel approach to ameliorate glomerular disease progression while simultaneously reducing thromboembolic risk, a life-threatening complication of glomerular disease. Importantly, the chronic model data demonstrates that DOACs are renoprotective when started after proteinuria is established.

Funding

• NIDDK Support