Kidney Denervation

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Hans Imboden - One of the best experts on this subject based on the ideXlab platform.

Jürgen M. Bohlender - One of the best experts on this subject based on the ideXlab platform.

Aleš Linhart - One of the best experts on this subject based on the ideXlab platform.

  • The effect of renal Denervation in an experimental model of chronic renal insufficiency, The REmnant Kidney Denervation In Pigs study (REDIP study)
    Journal of translational medicine, 2017
    Co-Authors: Miroslav Chochola, Mikuláš Mlček, Petr Neužil, Josef Marek, Štěpán Havránek, Sylvie Kuchynková, Zdeňka Fingrová, Kao-hsuan Aimee Huang, Aleš Linhart
    Abstract:

    Renal Denervation (RDN) is a promising therapeutic method in cardiology. Its currently most investigated indication is resistant hypertension. Other potential indications are atrial fibrillation, type 2 diabetes mellitus and chronic renal insufficiency among others. Previous trials showed conflicting but promising results, but the real benefits of RDN are still under investigation. Patients with renal insufficiency and resistant hypertension are proposed to be a good target for this therapy due to excessive activation of renal sympathetic drive. However, only limited number of studies showed benefits for these patients. We hypothesize that in our experimental model of chronic Kidney disease (CKD) due to ischemia with increased activity of the renin–angiotensin–aldosterone system (RAAS), renal Denervation can have protective effects by slowing or blocking the progression of renal injury. An experimental biomodel of chronic renal insufficiency induced by ischemia was developed using selective renal artery embolization (remnant Kidney porcine model). 27 biomodels were assessed. Renal Denervation was performed in 19 biomodels (denervated group), and the remaining were used as controls (n = 8). The extent of renal injury and reparative process between the two groups were compared and assessed using biochemical parameters and histological findings. Viable remnant Kidney biomodels were achieved and maintained in 27 swine. There were no significant differences in biochemical parameters between the two groups at baseline. Histological assessment proved successful RDN procedure in all biomodels in the denervated group. Over the 7-week period, there were significant increases in serum urea, creatinine, and aldosterone concentration in both groups. The difference in urea and creatinine levels were not statistically significant between the two groups. However, the level of aldosterone in the denervated was significantly lower in comparison to the controls. Histological assessment of renal arteries showed that RDN tends to produce more damage to the arterial wall in comparison to vessels in subjects that only underwent RAE. In addition, the morphological damage of Kidneys, which was expressed as a ratio of damaged surface (or scar) to the overall surface of Kidney, also did not show significant difference between groups. In this study, we were not able to show significant protective effect of RDN alone on ischemic renal parenchymal damage by either laboratory or histological assessments. However, the change in aldosterone level shows some effect of renal Denervation on the RAAS system. We hypothesize that a combined blockade of the RAAS and the sympathetic system could provide more protective effects against acute ischemia. This has to be further investigated in future studies.

  • The effect of renal Denervation in an experimental model of chronic renal insufficiency, The REmnant Kidney Denervation In Pigs study (REDIP study)
    BMC, 2017
    Co-Authors: Jean-claude Lubanda, Miroslav Chochola, Mikuláš Mlček, Petr Neužil, Josef Marek, Štěpán Havránek, Sylvie Kuchynková, Zdeňka Fingrová, Kao-hsuan Aimee Huang, Aleš Linhart
    Abstract:

    Abstract Background Renal Denervation (RDN) is a promising therapeutic method in cardiology. Its currently most investigated indication is resistant hypertension. Other potential indications are atrial fibrillation, type 2 diabetes mellitus and chronic renal insufficiency among others. Previous trials showed conflicting but promising results, but the real benefits of RDN are still under investigation. Patients with renal insufficiency and resistant hypertension are proposed to be a good target for this therapy due to excessive activation of renal sympathetic drive. However, only limited number of studies showed benefits for these patients. We hypothesize that in our experimental model of chronic Kidney disease (CKD) due to ischemia with increased activity of the renin–angiotensin–aldosterone system (RAAS), renal Denervation can have protective effects by slowing or blocking the progression of renal injury. Methods An experimental biomodel of chronic renal insufficiency induced by ischemia was developed using selective renal artery embolization (remnant Kidney porcine model). 27 biomodels were assessed. Renal Denervation was performed in 19 biomodels (denervated group), and the remaining were used as controls (n = 8). The extent of renal injury and reparative process between the two groups were compared and assessed using biochemical parameters and histological findings. Results Viable remnant Kidney biomodels were achieved and maintained in 27 swine. There were no significant differences in biochemical parameters between the two groups at baseline. Histological assessment proved successful RDN procedure in all biomodels in the denervated group. Over the 7-week period, there were significant increases in serum urea, creatinine, and aldosterone concentration in both groups. The difference in urea and creatinine levels were not statistically significant between the two groups. However, the level of aldosterone in the denervated was significantly lower in comparison to the controls. Histological assessment of renal arteries showed that RDN tends to produce more damage to the arterial wall in comparison to vessels in subjects that only underwent RAE. In addition, the morphological damage of Kidneys, which was expressed as a ratio of damaged surface (or scar) to the overall surface of Kidney, also did not show significant difference between groups. Conclusions In this study, we were not able to show significant protective effect of RDN alone on ischemic renal parenchymal damage by either laboratory or histological assessments. However, the change in aldosterone level shows some effect of renal Denervation on the RAAS system. We hypothesize that a combined blockade of the RAAS and the sympathetic system could provide more protective effects against acute ischemia. This has to be further investigated in future studies

Hideya Saito - One of the best experts on this subject based on the ideXlab platform.

  • changes in renal blood flow in response to sympathomimetics in the rat transplanted and denervated Kidney
    International Journal of Urology, 1999
    Co-Authors: Ken Morita, Toshimori Seki, Katsuya Nonomura, Tomohiko Koyanagi, Mitsuhiro Yoshioka, Hideya Saito
    Abstract:

    BACKGROUND Renal Denervation and re-innervation may affect vascular responses to sympathomimetics, which may play a role in the maintainance of renal blood flow (RBF) following renal transplantation. The purpose of the present study was to elucidate pharmacological alteration of the renal sympathetic response following Kidney transplantation. Using the rat Kidney transplantation model, we focused on responses to various sympathomimetics in order to investigate the effects of sympathetic Denervation and functional remodulation mechanisms in the transplanted Kidney. METHODS Male isogenic rats underwent unilateral Kidney Denervation or Kidney transplantation accompanied by unilateral native nephrectomy. Renal blood flow was evaluated using a laser Doppler flow meter following bolus injection of 50 microg/kg dopamine and continuous infusion of 60 microg/min phenylephrine (PE) at 0, 30, 60, 90 and 240 days after transplantation as well as at 30 days after Denervation. RESULTS Bolus injection of dopamine (50 microg/kg) induced an initial reduction in RBF (that of alpha-adrenoceptors) followed by a long-lasting increase in RBF (that of beta-adrenoceptors) in the native Kidney. In grafted or denervated Kidneys, the dopamine-induced decrease in RBF mediated by alpha-adrenoceptors was markedly enhanced while the increase in RBF mediated by an action of dopamine on beta-adrenoceptors was blunted. The effects of the post-transplant period on vascular responses to dopamine were significant, but not completely synchronized with the native Kidney, even at 240 days. Continuous infusion of PE (60 microg/min) produced a gradual increase in RBF in the native Kidney, whereas a sudden reduction (i.e. breakthrough in autoregulation) was observed in the denervated and transplanted Kidney. CONCLUSIONS The responses to sympathomimetics in the grafted Kidney were shifted towards flow reduction (i.e. enhanced vasoconstriction via stimulation of alpha-adrenoceptors and blunted vasodilatation via stimulation of beta-adrenoceptors. This functional impairment was recovered in a time-dependent manner. In addition, the hemodynamic autoregulation system in the Kidney deteriorated following transplantation or Denervation.

Jürg Nussberger - One of the best experts on this subject based on the ideXlab platform.

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