Renal denervation mitigates renal dysfunction in a rat model of tacrolimus-induced nephrotoxicity

Abstract

Tacrolimus, a macrolide calcineurin inhibitor, is the most widely used immune suppressant medication after solid-organ transplant in humans, however, its use is complicated by nephrotoxicity and the development of chronic kidney disease. Interestingly, transplanted kidneys, which lack renal nerves, enjoy a relative protection from tacrolimus-induced nephrotoxicity. Consistent with this clinical observation, we explored the hypothesis that renal denervation would protect against the development of kidney disease in a rat model of tacrolimus-induced nephrotoxicity.To test this hypothesis, Sprague-Dawley rats underwent either total renal denervation (TRDN) or sham denervation and thereafter were injected with either vehicle (corn oil) or tacrolimus (2 mg/kg) for 14 days. At the end of this protocol plasma blood urea nitrogen (BUN), a marker of renal filtration function, was substantially lower in TRDN rats treated with tacrolimus than in their sham counterparts (24 vs 36 mg/dL, respectively). Similarly, TRDN rats treated with tacrolimus demonstrated substantially less renal fibrosis and glomerular damage than their sham counterparts as demonstrated by trichrome staining and PAS staining.Together our results demonstrate that total renal denervation is protective against the development of tacrolimus-induced nephrotoxicity. This finding suggests that renal denervation of the kidneys of solid-organ transplant recipients could substantially decrease the burden of chronic kidney disease in the transplant population. R01 HL116476. T32HL144472. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.