ReviewTotal renal denervation reduces sympathoexcitation to different target organs in a model of chronic kidney disease

- Differential impact of renal denervation on the degree of sympathoexcitation to other targets in a CKD model.
- Renal denervation decreased blood pressure and sympathoexcitation to splanchnic and lumbar beds in a CKD model.
- Renal denervation was effective in improving proteinuria and reducing plasma creatinine in experimental renal disease.

It is known that increased sympathetic nerve activity in chronic kidney disease (CKD) progressively worsens kidney function and hypertension. We tested the hypothesis that total renal denervation contributes to reduce sympathetic activation to different beds and improves renal function in 5/6 nephrectomy model of CKD in male Wistar rats. After eight weeks of 5/6 nephrectomy surgery there was an increase in mean arterial pressure (CKD 179 ± 22 mm Hg, n = 6 vs. control animals 108 ± 9; p < 0.05, n = 6) with no changes in heart rate (HR). Sympathetic nerve activity was increased at different levels to the remaining kidney, splanchnic and lumbar beds compared to control (CTL) group (CKD rSNA: 150 ± 50, n = 9 vs. CTL 96 ± 15, n = 9; CKD sSNA: 129 ± 51, n = 5 vs. CTL 34 ± 14, n = 6; CKD lSNA: 203 ± 35, n = 8 vs. CTL 146 ± 21, spikes/s, n = 7, p < 0.05). Three weeks after total renal denervation (DNX) MAP was normalized in the CKD rats (124 ± 19 mm Hg, n = 5, p < 0.05), with no change in HR. The lSNA was normalized (151 ± 40, n = 5, vs. CKD 203 ± 35 spikes/s, n = 8) and sSNA was decreased in 49% (64 ± 34, n = 5 vs. CKD 129 ± 51 spikes/s, n = 5, p < 0.05). Renal function, assessed by creatinine plasma levels was improved after renal denervation (CKD 1.50 ± 0.64, n = 8; vs. CKD + DNX 0.82 ± 0.22 mg/mL, n = 8, p < 0.05). These findings demonstrate that renal nerves contribute to the maintenance of hypertension in CKD by increasing sympathoexcitation to other beds.