The effects of acute renal denervation on kidney perfusion and metabolism in experimental septic shock

Post, Emiel Hendrik; Su, Fuhong; Taccone, Fabio Silvio; Herpain, Antoine; Créteur, Jacques; Backer, Daniel De; Vincent, Jean‐Louis

doi:10.1186/s12882-017-0586-6

Cited by 5 publications

(10 citation statements)

References 62 publications

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“…This impairment of kidney perfusion was associated with more pronounced anaerobic metabolism in the renal cortex. In another study by our group, an attempt to improve renal perfusion by renal denervation resulted in a temporary increase in RBF during normotensive sepsis (51). However, after the onset of shock, RBF decreased to control levels, and the cortical lactate/pyruvate ratio appeared more pronounced in the denervated animals, which suggests that flow was less efficiently matched to metabolism.…”

Section: Discussionmentioning

confidence: 90%

Renal autoregulation in experimental septic shock and its response to vasopressin and norepinephrine administration

Post

Shinotsuka

et al. 2018

Journal of Applied Physiology

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Evidence suggests that septic shock patients with chronic arterial hypertension may benefit from resuscitation targeted to achieve higher blood pressure values than other patients, possibly as a result of altered renal autoregulation. The effects of different vasopressor agents on renal autoregulation may be important in this context. We investigated the effects of arginine vasopressin (AVP) and norepinephrine (NE) on renal autoregulation in ovine septic shock. Sepsis was induced by fecal peritonitis. When shock developed (decrease in mean arterial pressure to <65 mmHg and no fluid responsiveness), animals were randomized to receive NE or AVP in a crossover design. Before the switch to the second vasopressor, the first vasopressor was discontinued for 30 min to ensure complete washout of the first vasopressor. Renal autoregulation was evaluated by recording the change in renal blood flow (RBF) in response to manual, stepwise reductions in renal inflow pressure. In this model, the lower limit of renal autoregulation was not significantly altered 6 h after sepsis induction (59 ± 9 vs. 64 ± 7 mmHg at baseline, P = 0.096). After development of shock, the autoregulatory threshold was lower with AVP than with NE (59 ± 5 vs. 65 ± 7 mmHg, P = 0.010). However, RBF was higher with NE both at the start of autoregulatory measurements (206 ± 58 vs. 170 ± 52 ml/min; P = 0.049) and at the autoregulatory threshold (191 ± 53 vs. 150 ± 47 ml/min; P = 0.008). As vasopressors may have different effects on renal autoregulation, blood pressure management in patients with septic shock should be individualized and take into account drug-specific effects. NEW & NOTEWORTHY Septic shock patients with chronic arterial hypertension may benefit from higher blood pressure targets due to underlying deficits in renal autoregulatory efficiency. The current study is the first to show that the choice of vasopressor agent can differentially affect renal autoregulation. These findings may contribute to more personalized blood pressure management in patients with septic shock.

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Section: Discussionmentioning

confidence: 90%

Renal autoregulation in experimental septic shock and its response to vasopressin and norepinephrine administration

Post

Shinotsuka

et al. 2018

Journal of Applied Physiology

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“…15,16 RDN prevents these effects, and thereby reduces blood pressure. 14 Glomerular perfusion and filtration are central parameters of kidney function and altered regulation after RDN might affect kidney diseases itself. However, the effects of denervation on the GFR in humans have not yet been definitively determined.…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, the contralateral kidneys contained more UPEC than kidneys of sham-operated mice (Figure 4C). This can be explained by a reduced glomerular filtration in contralateral kidneys (Figure 1, F to G) to compensate for the higher urine www.jasn.org RAPID COMMUNICATIONS production by denervated kidneys, 14 which incapacitated bacterial flushing in contralateral kidneys profoundly. Finally, the ratio of neutrophils per CFU in a kidney was higher in denervated kidneys compared with contralateral controls (Supplemental Figure 6), suggesting that the higher perfusion of denervated kidneys allows for better recruitment of neutrophils from the circulation.…”

Section: Resultsmentioning

confidence: 99%

“…[9][10][11][12] Renal sympathetic signals cause hemodynamic adjustments that result in electrolyte and fluid retention, contributing to the maintenance of blood pressure, for example, in the case of flightor-fight reactions. This is either achieved directly by autonomous vasoconstriction of the afferent arteries 13,14 or indirectly by stimulating glomerular b1-adrenergic receptors that induce renin production and release. 15 In consequence, the reninangiotensin-aldosterone system will reduce glomerular perfusion and filtration, and thereby retain fluid.…”

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confidence: 99%

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Renal Denervation Exacerbates LPS- and Antibody-induced Acute Kidney Injury, but Protects from Pyelonephritis in Mice

Böhner

Jacob

Heuser

et al. 2021

JASN

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• Background: Renal denervation (RDN) is an invasive intervention to treat drug-resistant arterial hypertension. Its therapeutic value is contentious. Here we examined the effects of RDN on inflammatory and infectious kidney disease models in mice. • Methods: Mice were unilaterally or bilaterally denervated, or sham operated, then three disease models were induced: nephrotoxic nephritis (NTN, a model for crescentic glomerulonephritis), pyelonephritis and acute endotoxemic kidney injury (as a model for septic kidney injury). Analytical methods included measurement of renal glomerular filtration, proteinuria, flow cytometry of renal immune cells, immunofluorescence microscopy and 3D imaging of optically cleared kidney tissue by light-sheet-fluorescence-microscopy followed by algorithmic analysis. • Results: Unilateral RDN increased glomerular filtration in denervated kidneys but decreased it in the contralateral kidneys. In the NTN model, more nephritogenic antibodies were deposited in glomeruli of denervated kidneys, resulting in stronger inflammation and injury in denervated compared to contralateral non-denervated kidneys. Also intravenously injected LPS increased neutrophil influx and inflammation in the denervated kidneys, both after unilateral and bilateral RDN. When we induced pyelonephritis in bilaterally denervated mice, both kidneys contained less bacteria and neutrophils. In unilaterally denervated mice, pyelonephritis was attenuated and intrarenal neutrophil numbers were lower in the denervated kidneys. The non-denervated contralateral kidneys harbored more bacteria, even compared to sham-operated mice, and showed the strongest influx of neutrophils. • Conclusions: Our data suggest that the increased perfusion and filtration in denervated kidneys can profoundly influence concomitant inflammatory diseases. Deposition of circulating nephritic material is higher, and hence antibody- and endotoxin-induced kidney injury was aggravated in mice. Pyelonephritis was attenuated in denervated murine kidneys, because the higher glomerular filtration facilitated better flushing of bacteria with the urine, at the expense of contralateral, non-denervated kidneys in case of unilateral denervation.

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“…We attributed the impaired autoregulation during esmolol infusion to a reduced RPP rather than to damaged autoregulation mechanisms. These perfusion deficits indeed play an important role in the development of renal dysfunction in sepsis (Post, Su, et al, ). Herein, this deficit is largely explained by a markedly increased CVP, resulting in a significantly reduced RPP and RBF (Pearson correlation p < .05).…”

Section: Discussionmentioning

confidence: 99%

β‐Blockade attenuates renal blood flow in experimental endotoxic shock by reducing perfusion pressure

Loon

Rongen

Hoeven³

et al. 2019

Physiol Rep

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Clinical data suggests that heart rate (HR) control with selective β1‐blockers may improve cardiac function during septic shock. However, it seems counterintuitive to start β‐blocker infusion in a shock state when organ blood flow is already low or insufficient. Therefore, we studied the effects of HR control with esmolol, an ultrashort‐ acting β1‐selective adrenoceptor antagonist, on renal blood flow (RBF) and renal autoregulation during early septic shock. In 10 healthy sheep, sepsis was induced by continuous i.v. administration of lipopolysaccharide, while maintained under anesthesia and mechanically ventilated. After successful resuscitation of the septic shock with fluids and vasoactive drugs, esmolol was infused to reduce HR with 30% and was stopped 30‐min after reaching this target. Arterial and venous pressures, and RBF were recorded continuously. Renal autoregulation was evaluated by the response in RBF to renal perfusion pressure (RPP) in both the time domain and frequency domain. During septic shock, β‐blockade with esmolol significantly increased the pressure dependency of RBF to RPP. Stopping esmolol showed the reversibility of the impaired renal autoregulation. Showing that clinical diligence and caution are necessary when treating septic shock with esmolol in the acute phase since esmolol reduced RPP to critical values thereby significantly reducing RBF.

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The effects of acute renal denervation on kidney perfusion and metabolism in experimental septic shock

Cited by 5 publications

References 62 publications

Renal autoregulation in experimental septic shock and its response to vasopressin and norepinephrine administration

Renal autoregulation in experimental septic shock and its response to vasopressin and norepinephrine administration

Renal Denervation Exacerbates LPS- and Antibody-induced Acute Kidney Injury, but Protects from Pyelonephritis in Mice

β‐Blockade attenuates renal blood flow in experimental endotoxic shock by reducing perfusion pressure

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