The Effects of Fenoldopam on Renal Function and Metabolism in an Ovine Model of Septic Shock

Taccone

et al. 2017

BMC Nephrol

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BackgroundPerfusion deficits likely play an important role in the development of renal dysfunction in sepsis. Renal denervation may improve kidney perfusion and metabolism.MethodsWe randomized 14 female sheep to undergo bilateral surgical renal denervation (n = 7) or sham procedure (n = 7) prior to induction of sepsis. Renal blood flow (RBF) was measured with a pre-calibrated flowprobe. Laser Doppler probes were implanted to measure cortical and medullary perfusion. Cortical glucose, lactate and pyruvate levels were measured using the microdialysis technique. Creatinine clearance was determined. Sepsis was induced by peritonitis and fluid resuscitation was provided to avoid hypovolemia.ResultsRBF and cortical perfusion were higher in the denervated group during the first 6 h after induction of sepsis (P < 0.001 and P < 0.05, respectively), while medullary perfusion decreased similarly in both groups. After hypotension developed, RBF decreased to similar levels in both groups. Cortical pyruvate and lactate levels were lower in the denervated animals (P < 0.001 and P < 0.001, respectively). There were no differences between groups in creatinine clearance, urine output or time to oliguria.ConclusionDenervation thus caused an early increase in RBF that was distributed towards the kidney cortex. Although associated with an attenuation of early cortical metabolic alterations, denervation failed to prevent the deterioration in renal function.

Section: Discussionsupporting

confidence: 43%

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

Taccone

et al. 2017

BMC Nephrol

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“…In a recent study by our group in the same model as the present study, renal hypoperfusion was associated with an increase in the lactate-to-pyruvate ratio in the renal cortex, suggesting the presence of anaerobic lactate production (52). Also in this model, administration of the selective dopamine-1 receptor agonist fenoldopam did not preserve RBF (53). Moreover, in animals that received the drug at high-dose, RBF was lower after 18 h of sepsis than in control animals.…”

Section: Discussionsupporting

confidence: 50%

“…Porcine models with generalized atherosclerosis exist, but the animals do not appear to display any arterial hypertension (47,68). Therefore, we decided to test our hypothesis in the ovine model regularly used by our group (27,53). This does mean, however, that our results may lack some external validity, and studies that account for vascular comorbidity are necessary before any clinical recommendations can be made.…”

Section: Discussionmentioning

confidence: 99%

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

Journal of Applied Physiology

Shinotsuka

et al. 2018

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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.

“…50 Recent work by our group showed that the selective dopamine-1 receptor agonist, fenoldopam, was ineffective at preserving RBF in a sheep model of septic shock. 51 Interventional clinical studies. Several small, nonblinded, interventional studies in human septic shock have reported a beneficial effect on urine output [52][53][54] and creatinine clearance [55][56][57] when using norepinephrine to increase RPP (Table 3).…”

Section: Systemic Hemodynamics Rbf and Kidney Functionmentioning

confidence: 99%

Renal perfusion in sepsis: from macro- to microcirculation

Kellum

Bellomo

et al. 2017

Kidney International

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151

104

The pathogenesis of sepsis-associated acute kidney injury is complex and likely involves perfusion alterations, a dysregulated inflammatory response, and bioenergetic derangements. Although global renal hypoperfusion has been the main target of therapeutic interventions, its role in the development of renal dysfunction in sepsis is controversial. The implications of renal hypoperfusion during sepsis probably extend beyond a simple decrease in glomerular filtration pressure, and targeting microvascular perfusion deficits to maintain tubular epithelial integrity and function may be equally important. In this review, we provide an overview of macro- and microcirculatory dysfunction in experimental and clinical sepsis and discuss relationships with kidney oxygenation, metabolism, inflammation, and function.