A6532 Partial reinnervation of efferent renal sympathetic nerves 30 months after radiofrequency catheter-based renal denervation in sheep with hypertensive chronic kidney disease

Abstract

Objectives: Radiofrequency catheter-based renal denervation (RDN) maybe effective in reducing blood pressure (BP) in resistant hypertension. Regrowth of renal nerves and restoration of function occurs from 5.5 months after RDN in normotensive sheep with regrowth and function of nerves restored to levels of intact by 11 months. Our studies in sheep with hypertensive CKD show BP is reduced at 2 and 5 months after RDN. In the present study we examined 1) if the reduction in BP was sustained and 2) the extent of regrowth of renal nerves at 30 months after RDN in the same cohort of sheep. Methods: At 10 months sheep underwent RDN using the Symplicity Flex catheter (control-RDN, n = 8; CKD-RDN, n = 7) or sham procedure (control-intact, n = 6; CKD-intact, n = 7). BP was measured in conscious sheep via carotid arterial catheter. Kidneys underwent immunohistochemical staining of renal efferent nerves (tyrosine hydroxlylase) at 30 months after RDN. Results: BP was higher in CKD-intact compared with control-intact but was less in CKD-RDN than CKD-intact (BP (mmHg); control-intact; 86 ± 1, control-RDN; 87 ± 4, CKD-intact; 95 ± 6, CKD-RDN; 83 ± 4). TH (percentage of kidney section volume) was 60% greater in CKD-intact compared with control-intact but was 2-fold less in CKD-RDN than CKD-intact (Fig 1). There was no difference in BP and TH staining between control-intact and control-RDN sheep. Conclusion: There is increased sympathetic innervation in this model of hypertensive-CKD, which may be driving elevated BP. Reinnervation occurred in both normotensive and hypertensive sheep after RDN. However, restoration to levels of intact animals was only observed in normotensive sheep, with only partial restoration observed in CKD sheep at 30 months post-RDN. This may account for the sustained reduction in BP observed following RDN.