Abstract: TH-PO0932
TRPC6, a Novel Target for BK Infection
Session Information
- Transplantation: Clinical - Glomerular Diseases, Infections, and Rejection
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Polat, Onur K, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Israni, Ajay K., The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Koss, Kyle Michael, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
Background
BK polyomavirus-associated nephropathy (BKPyVAN) affects 3–5% of the 25,000 annual U.S. kidney transplant recipients, causing >50% graft loss and a $5 billion burden (CDC, 2025). Reducing immunosuppression risks rejection, highlighting the need for targeted antivirals. Tacrolimus worsens BKPyV infection vs. cyclosporine, but mechanisms are unclear. JC polyomavirus uses 5-HT2a receptor and TRPC6 for entry. We hypothesize tacrolimus enhances TRPC6 activity, promoting BKPyV endocytosis via calcium influx and caveolin-1 stabilization similar to JCPyV. This project targets TRPC6 to reduce graft loss and inform polyomavirus prophylaxis.
Methods
Cell culture, electrophysiology, calcium imaging and database analysis were employed to investigate the effect of tacrolimus mediated BKPyV excarbation.
Results
TriNetX analysis (n=37,537) showed tacrolimus increased BKPyV risk vs. cyclosporine in kidney transplant recipients. Tacrolimus (n=20,099) had 7.6% prevalence and 16.7% incidence; cyclosporine (n=2,562) had 3.8% prevalence and 13.0% incidence (p<0.0001). Other viral infections were higher with tacrolimus (17.4%, 28.71%) vs. cyclosporine (73.3%, 15.0%) (p<0.0001). No calcineurin inhibitors (n=5,676) had the lowest BKPyV rates (17.0%, 5.8%).
Conclusion
Targeting TRPC6 may reduce BKPyV infection and graft loss in kidney transplant recipients.
Prevalence and cumulative incidence of BKPyV with tacrolimus and cyclosporine
| Immunosuppresive regimen | Cohort Size | Kidney Transplant Infection (BKPyV) | Other viral agents |
| Tacrolimus | 20,099 | Prevalence: 7.6% (1228/20,099) Cum. Incidence: 16.7% (no CI) Prevalence: p < 0.0001 Cum. Incidence: p < 0.0001 | Prevalence: 17.4% (5088/20,099) Cum. Incidence: 28.71% (no CI) Prevalence: p < 0.0001 Cum. Incidence: p < 0.0001 |
| Cyclosporine | 2,562 | Prevalence: 3.8% (38/562) Cum. Incidence: 13.0% (95% CI: 7.8–18.0) Prevalence: p < 0.0001 Cum. Incidence: p < 0.0001 | Prevalence: 73.3% Cum. Incidence: 15.0% (95% CI: 13.8–16.0) Prevalence: p < 0.0001 Cum. Incidence: p > 0.0055 |
| No Calcineurin Inhibitors | 5,676 | Prevalence: 17.0% (105/676) Cum. Incidence: 5.8% (95% CI: 3.8–7.4) Prevalence: p < 0.0001 Cum. Incidence: p < 0.0001 | Prevalence: 5.37% Cum. Incidence: 14.0% (95% CI: 11.8–21.77) Prevalence: p < 0.0001 Cum. Incidence: p > 0.0055 |