Renal Denervation Mitigates Hypertension and Improves Glomerular Filtration Rate in an Adult Rat Model of Polycystic Kidney Disease

Abstract

Polycystic kidney disease (PKD) remains the most common form of inherited chronic kidney disease failure, and the only cure is renal transplantation. PKD is also strongly associated with increased arterial pressure (AP) and peripheral sympathetic nerve activity (SNA). Recent studies have shown ablation of renal nerves, or renal denervation (RDN), may be effective treatment for varying forms of HTN and renal disease; however, the role and mechanism for renal nerves in preexisting, PKD‐associated renal dysfunction and HTN remain unclear. Therefore, the aim of study was investigate the role of renal nerves in adult PKD, where we hypothesized RDN would reduce AP, lower peripheral sympathetic tone, and improve glomerular filtration rate (GFR) in the adult PKD rat.To test this hypothesis, 6‐month‐old male and female PKD rats underwent bilateral surgical RDN or sham surgery (Total n=18; 9/group; 3M/6F). RDN was achieved by surgical dissection followed by perivascular application of 10%(v/v) phenol. Cardiovascular parameters were recorded by radiotelemetry which was implanted two weeks prior to experimental treatment. Peripheral sympathetic tone was estimated by depressor response to acute ganglionic blockade (GB). GFR was assessed in unrestrained, conscious rats by acute FITC‐sinistrin clearance. Two weeks following RDN/Sham, rats were euthanized and tissues were collected for further analysis. Data was analyzed by a two‐way ANOVA, across sex and treatment groups (α=0.05). Data presented as mean+SEM.At baseline, no differences in 24‐hour mean AP (132 ± 2 vs. 129 ± 3mmHg), acute GB response (39 ± 3 vs. 42 ± 4ΔmmHg), nor GFR (0.93 ± 0.06 vs. 0.91 ± 0.04 mL/min/100g) were detected between treatment groups. No sex differences at baseline were detected at baseline. Two weeks following treatment, 24‐hour mean AP was lowered in RDN (121 ± 1.5mmHg) vs. sham (130 ± 2.8ΔmmHg), and no effect of sex was observed. Similarly, depressor response to GB was halved in RDN (−16 ± 2 ΔmmHg) compared to sham (−32 ± 3 ΔmmHg), and no effect of sex was detected. GFR was significantly increased in RDN vs. sham (1.18 ± 0.06 vs. 0.84 ± 0.08 mL/min/100g), and no effect of sex was detected. Lastly, no difference in renal cystic index was detected between RDN and sham (8.27 ± 1.39 vs. 8.74 ± 0.90%), and differences between male and female groups were observed.Together, these data support our initial hypothesis, where RDN effectively lowered AP and peripheral sympathetic tone in the PKD rat. This was paired with a significant increase in GFR in these animals, indicating an improvement in renal function despite no observable effect on renal cystic index Of note, the efficacy of RDN was similar across male and female groups. Further studies are underway to determine if the cardiovascular and renal effects observed in this study are primarily mediated by the ablation of the efferent or afferent nerves.Support or Funding InformationThis project was supported in part by NIH 1K99HL141650 (CTB) and R01HL116476 (JWO).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.