Blunted natriuretic response to saline loading in sheep with hypertensive kidney disease following radiofrequency catheter-based renal denervation

Reetu R Singh,Clive N May,Karen M Moritz,Kate M Denton,Markus P Schlaich,Harshil Singh,Zoe Mcardle,Lindsea C Booth,Geoffrey A Head

doi:10.1038/s41598-021-94221-5

Abstract

Renal sympathetic nerves contribute to renal excretory function during volume expansion. We hypothesized that intact renal innervation is required for excretion of a fluid/electrolyte load in hypertensive chronic kidney disease (CKD) and normotensive healthy settings. Blood pressure, kidney hemodynamic and excretory response to 180 min of isotonic saline loading (0.13 ml/kg/min) were examined in female normotensive (control) and hypertensive CKD sheep at 2 and 11 months after sham (control-intact, CKD-intact) or radiofrequency catheter-based RDN (control-RDN, CKD-RDN) procedure. Basal blood pressure was ~ 7 to 9 mmHg lower at 2, and 11 months in CKD-RDN compared with CKD-intact sheep. Saline loading did not alter glomerular filtration rate in any group. At 2 months, in response to saline loading, total urine and sodium excretion were ~ 40 to 50% less, in control-RDN and CKD-RDN than intact groups. At 11 months, the natriuretic and diuretic response to saline loading were similar between control-intact, control-RDN and CKD-intact groups but sodium excretion was ~ 42% less in CKD-RDN compared with CKD-intact at this time-point. These findings indicate that chronic withdrawal of basal renal sympathetic activity impairs fluid/electrolyte excretion during volume expansion. Clinically, a reduced ability to excrete a saline load following RDN may contribute to disturbances in body fluid balance in hypertensive CKD.

Highlights

Renal sympathetic nerves contribute to renal excretory function during volume expansion
Given that renal denervation (RDN) is clinically being trialed for treatment of h ypertension[16,17,18,19] and chronic kidney disease (CKD)[3,20,21,22,23,24], the observations demonstrating that RDN may promote fluid/electrolyte retention in response to volume expansion is concerning
On the day of saline loading, at both time-points, basal mean arterial pressure (MAP) was higher in CKD-intact group compared with control-intact, and compared with CKD-RDN groups, but MAP was similar between control-intact and control-RDN groups (MAP mmHg; 2 months; CKDintact: 90 ± 1, control-intact: 83 ± 1, P = 0.0006, CKD-RDN: ± 1, P < 0.0001, control-RDN: ± 1, 11 months; CKD-intact: 94 ± 1, control-intact: ± 1, P = 0.0009, CKD-RDN: ± 1, P = 0.002, control-RDN: 85 ± 1, Fig. 1a,b)

Summary

Introduction

Renal sympathetic nerves contribute to renal excretory function during volume expansion. At 11 months, the natriuretic and diuretic response to saline loading were similar between control-intact, control-RDN and CKD-intact groups but sodium excretion was ~ 42% less in CKD-RDN compared with CKD-intact at this time-point These findings indicate that chronic withdrawal of basal renal sympathetic activity impairs fluid/electrolyte excretion during volume expansion. A major limitation of the studies mentioned is that, either the examinations have been performed in the short-term (acute studies) or because of the significant time-range post RDN, the findings are potentially influenced by reinnervation of the renal nerves It is unclear from these studies whether the impairment in fluid/electrolyte excretion following RDN are a short-term defect, or if these changes are sustained over the long-term. To clearly understand the contribution of renal nerves and reinnervation of the renal nerves on excretion of a fluid and electrolyte load, it is important to examine whether RDN affects excretory function in the same animal long-term

Methods

Results

Discussion

Conclusion