Kidney Week

Abstract: TH-PO0406

Oral Cannabidiol Modulates Kidney Immune and Metabolic Pathways in Lupus Nephritis

Session Information

• Glomerular Diseases: Autoimmune Diseases
  October 22, 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

• Gisch, Debora L., Indiana University School of Medicine, Indianapolis, Indiana, United States

Debora L. Gisch, PhD

• Koyama, Sachiko, Indiana University School of Medicine, Indianapolis, Indiana, United States

Sachiko Koyama, PhD

• Yennapureddy, Soumya, Indiana University School of Medicine, Indianapolis, Indiana, United States

Soumya Yennapureddy, MS

• Cheng, Ying-Hua, Indiana University School of Medicine, Indianapolis, Indiana, United States

Ying-Hua Cheng, MD, PhD

• Melo Ferreira, Ricardo, Indiana University School of Medicine, Indianapolis, Indiana, United States

Ricardo Melo Ferreira, PhD

• Sandoval, Ruben M., Indiana University School of Medicine, Indianapolis, Indiana, United States

Ruben M. Sandoval, MS

• Martinez-Irizarry, Michelle M., Indiana University School of Medicine, Indianapolis, Indiana, United States

Michelle M. Martinez-Irizarry, DVM

• Polidoro, Rafael, Indiana University School of Medicine, Indianapolis, Indiana, United States

Rafael Polidoro, PhD

• Dagher, Pierre C., Indiana University School of Medicine, Indianapolis, Indiana, United States

Pierre C. Dagher, MD, FASN

• Eadon, Michael T., Indiana University School of Medicine, Indianapolis, Indiana, United States

Michael T. Eadon, MD, FASN

Background

Lupus nephritis (LN) is driven by immune complex deposition, immune infiltration, and kidney-resident injury responses. Cannabidiol (CBD) has anti-inflammatory and immunomodulatory effects in humans. We investigated the effects of CBD on lupus associated kidney inflammation.

Methods

Female NZB/WF1 (N=16) lupus mice were treated with CBD for 6 weeks after presenting proteinuria (28 weeks). CBD was administered orally in food at 10 mg/kg/day. Kidney function was assessed by blood urea nitrogen (BUN; N=15), serum creatinine (N=15), and urine albumin to creatinine ratio (UACR; N=8) using the Wilcoxon Rank Sum test (P<0.05). Kidney single-cell RNA (scRNA-seq; N=3) and spatial transcriptomics (ST; N=3) characterized immune and compartment specific composition (Fisher’s exact test; adj. P<0.05) and gene expression (Wilcoxon; adjusted P<0.05), and fgsea enrichment analysis (adj. P<0.05).

Results

Untreated lupus mice had higher BUN (P<0.04) and a trend toward higher UACR (P<0.06), while serum creatinine was not different between groups. Kidney scRNA-seq and ST showed lower abundance of immune populations in CBD treatement, including resident (logOR=−3.5, 95%CI −4.3:−2.6), monocyte derived macrophages (−3, −3.4:−2.6), plasmacytoid dendritic (−1.3, −2.1:−0.4), NKT (−0.6, −0.9:−0.3), and T (−1.5, −1.7:−1.3) cells. Pathway analysis suggested lower enrichment of inflammatory signaling pathways in CBD treated kidneys when compared to untreated lupus. CBD treated samples showed relatively higher enrichment of oxidative metabolism and translation related pathways, particularly in epithelial compartments. Select Fc receptor and complement related pathways remained relatively enriched in specific immune cells.

Conclusion

Oral CBD treatment in murine LN was associated with lower BUN and a trend toward reduced UACR. Kidney profiling suggests CBD is associated with reduced immune cell abundance and differences in inflammatory and epithelial gene expression. These findings support further investigation of CBD as a modulator of kidney inflammation in LN.

Funding

• Other NIH Support