Renal Lymphatics in Early Diabetic Kidney Disease: Insights from 3D Imaging and Functional Assays
- Diabetic Kidney Disease: Basic - I
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
- Aktar, Tahmina, University College London Great Ormond Street Institute of Child Health, London, United Kingdom
- Jafree, Daniyal J., University College London Great Ormond Street Institute of Child Health, London, United Kingdom
- Walsh, Claire, UCL Centre for Advanced Biomedical Imaging, London, United Kingdom
- Gnudi, Luigi, King’s College London, London, United Kingdom
- Long, David A., University College London Great Ormond Street Institute of Child Health, London, United Kingdom
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, requiring dialysis or kidney transplant for patients’ survival. Consequently, new treatments are urgently required. Renal lymphatics have been implicated in DKD pathogenesis, but their specific role in the early stages of disease remains unclear. This study aims to address this need using advanced 3D imaging and in vitro functional assays.
DBA/2J mice, rendered diabetic by streptozotocin (STZ), were assessed four and twelve weeks post-STZ. We measured body and kidney weight, albuminuria, and inflammatory markers, and quantified lymphatic volume, diameter, and branches using 3-dimensional imaging and computer analysis. Human dermal lymphatic cells were exposed to serum from patients with a 20-year history of Type 1 diabetes, with or without DKD (presence of albuminuria), to study possible changes in their angiogenesis and migration capacities.
Although inflammation was elevated in diabetic mice at week four post-STZ, significant differences in lymphatic vessels, albuminuria, and kidney histology emerged only by week twelve. These changes included a marked expansion in lymphatic volume, diameter, and branches. Human lymphatic cells exposed to DKD+ serum showed longer tube lengths, more branches, and increased migration compared to cells exposed to DKD- serum.
Through 3D imaging, we identify an early-stage expansion of lymphatics in DKD, coinciding with the initiation of kidney damage. Furthermore, our cellular work indicates this may be a repair response, with enhanced tube formation and migratory capabilities in lymphatic cells exposed to serum from patients with DKD. These insights indicate that modulating kidney lymphatics may represent a novel therapeutic avenue for DKD.
- Private Foundation Support