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Kidney Week

Abstract: FR-PO730

Renal Denervation Is Protective Against the Development of CKD in a Rat Model of Tacrolimus Nephrotoxicity

Session Information

  • Transplantation: Basic
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 2101 Transplantation: Basic

Authors

  • Dayton, Alexander R., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Ruiz Lauar, Mariana, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Ross, Jaryd, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Evans, Louise Christine, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Osborn, John, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
Background

Tacrolimus is the most widely used immune suppressant medication after solid-organ transplant, however it is associated with significant morbidity due to nephrotoxicity and the development of chronic kidney disease. It has recently been appreciated that recipients of transplanted kidneys, which lack intact renal nerves, have a lower incidence of tacrolimus-induced nephrotoxicity. Here we present data demonstrating that denervated kidneys are protected from the development of tacrolimus nephrotoxicity in rats.

Methods

Male and female Sprague-Dawley rats (n=6) underwent either total renal denervation (TRDN) or sham denervation and were subsequently treated with either 2 mg/kg tacrolimus for 14 days or the equivalent dose of vehicle. At the end of treatment BUN was assessed as a marker of renal function. Histology was performed to assess renal fibrosis and glomerulosclerosis. RNA was extracted from the cortex and medulla, and then transcriptome was assessed.

Results

BUN was significantly lower in TRDN animals compared to sham(26 vs 38 mg/dl, p < 0.01). Additionally, medullary fibrosis was decreased in denervated rats. RNA-sequencing studies to further investigate the mechanism behind this protection are ongoing.

Conclusion

These findings present an exciting new avenue for the use of renal denervation – if confirmed these would provide the foundation for prophylactic renal denervation in non-renal transplant patients requiring tacrolimus.

Tacrolimus treatment for 14 days induces substantial renal dysfunction. Total renal denervation (TRDN) decreases BUN significantly compared to sham denervation.

Funding

  • Other NIH Support