Kidney Week

Abstract: SA-PO0003

Evaluating the Safety of a Novel SLIT/ROBO Pathway Inhibitor in Developing Kidneys Using a Preclinical Mouse Model

Session Information

• Development, Stem Cells, and Regenerative Medicine
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 700 Development, Stem Cells, and Regenerative Medicine

Authors

• Fang, Eric Yuting, Boston University, Boston, Massachusetts, United States

Eric Yuting Fang

• Dodge, Maura Clare, Boston University, Boston, Massachusetts, United States

Maura Clare Dodge, MS

• Woppmann, Claire N., Boston University, Boston, Massachusetts, United States

Claire N. Woppmann

• Yan, Kun, Boston University, Boston, Massachusetts, United States

Kun Yan

• Zhang, Simon, Boston University, Boston, Massachusetts, United States

Simon Zhang

• Fan, Xueping, Boston University, Boston, Massachusetts, United States

Xueping Fan, PhD

• Salant, David J., Boston University, Boston, Massachusetts, United States

David J. Salant, MD

• Kumar, Sudhir, Boston University, Boston, Massachusetts, United States

Sudhir Kumar, PhD

• Lu, Weining, Boston University, Boston, Massachusetts, United States

Weining Lu, MD, MS, FASN

Background

SLIT/ROBO signaling directs ureteric bud morphogenesis during kidney development and preserves podocyte adhesion and cytoskeletal integrity in mature glomeruli. A novel SLIT/ROBO inhibitor reduces podocyte loss and proteinuria in adult models of podocytopathy and is in phase 2 clinical testing for FSGS, but its safety in pregnancy and developing kidneys is unknown. We examined structural and glomerular marker outcomes after pre- and post–ureteric bud outgrowth exposure to this therapeutic in a mouse model.

Methods

Timed-pregnant C57BL/6 mice were randomized to receive subcutaneous SLIT/ROBO inhibitor (50 mg/kg) or saline (control). Dosing covered pre–ureteric bud formation (E5.5, E7.5, E9.5) and post–ureteric bud formation (E11.5, E13.5, E15.5). Offspring kidneys and urinary tracts were collected at postnatal day 1 (P1), P3, and P21 (weaning). Gross anatomy was assessed using dissection and stereomicroscopy. Histology was performed using PAS staining. Glomerular markers (nephrin, podocin, WT1) were evaluated by immunofluorescence (IF) and immunohistochemistry (IHC). Images were analyzed by light and confocal microscopy, and quantitative morphometry and marker-intensity measurements were performed using ImageJ.

Results

Litter size, pup viability, and gross renal and urinary tract anatomy were similar between treated and control groups. PAS histology at P1, P3, and P21 showed preserved nephrogenic zone structure, normal glomerular morphology, and intact tubular architecture in treated animals. Quantitative morphometry revealed no significant differences in mean glomerular cross-sectional area, glomerular density, or cortical thickness. IF/IHC for nephrin, podocin, and WT1 demonstrated comparable localization and signal intensity across groups at all time points. No treatment-related anomalies in WT1+ podocyte number per glomerulus were observed.

Conclusion

In this preclinical mouse model, maternal exposure to a SLIT/ROBO inhibitor administered before and after ureteric bud formation produced no detectable structural or histologic abnormalities in developing kidneys through weaning. These results support developmental renal safety in this model. Ongoing studies will assess long-term renal function, sex-specific effects, and dose–response relationships to further inform safety during pregnancy and early life.

Funding

• NIDDK Support