Abstract 045: Attenuated Natriuretic Response to Saline Loading in Sheep With Hypertensive Kidney Disease Following Radiofrequency Catheter-Based Renal Denervation

Abstract

In the present study, we examined the chronic effect of renal denervation (RDN) on the blood pressure (BP) and renal function in response to a slow-infused isotonic saline load. Normotensive (control) and hypertensive chronic kidney disease (CKD) sheep at 10 months of age underwent either a sham (control-intact; N=6, CKD-intact; N=7) or radiofrequency catheter-based RDN (control-RDN; N=7, CKD-RDN, N=7) procedure using the Symplicity catheter system. BP and renal function were measured during 3-h saline loading (0.9% NaCl, 0.13ml/kg/min) and 3-h recovery periods in animals at 2 and 11 months post-procedure. In this cohort of sheep, as previously reported, BP was reduced and GFR increased at 11 months in the CKD-RDN group. In response to saline loading, BP increased 3-5 mmHg in all groups. In response to saline loading sodium excretion increased in all groups. At 2 months post-procedure, the control-intact group excreted 66±7% of the sodium load over the 6-h period, whereas the response was exaggerated in the CKD-intact group (92±9%; P<0.001 vs. control-intact) but blunted in the RDN groups (control-RDN 32±5%; CKD-RDN 63±5%; both P<0.01 vs. intact). However, by 11 months post-procedure, the % excretion of the sodium load was similar in the intact (53±4%) and RDN (65±5%) control groups, but remained attenuated in the CKD-RDN group (33±6% P<0.001 vs. CKD-intact, 63±14%). Together these data indicate that (1) the normal suppression of RSNA activity during saline loading contributes to the rapid elimination of excess sodium and water, (2) following RDN the excretion of a saline load is attenuated and (3) this effect was maintained for 11 months in the CKD-RDN group indicating nerve regrowth is not complete. In conclusion, RDN in patients with hypertensive CKD may slow the return of extracellular fluid homeostasis in response to physiological challenges such as volume expansion.