Renal function and oxygen consumption during bacteraemia and endotoxaemia in rats

Heemskerk, A. E. J.; Huisman, Evelien; Lambalgen, A.A. van; Bos, G. C. van den; Hennekes, M.; Thijs, L. G.; Tangelder, G. J.

doi:10.1093/ndt/12.8.1586

Cited by 30 publications

(29 citation statements)

References 5 publications

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“…Prior studies have shown that in the first 1-4 hours after intravenous endotoxin exposure, intrarenal oxygen consumption is unchanged despite reduced delivery (35)(36)(37). Our results at a later time may reflect a transition to mitochondrial dysfunction as endotoxemia progresses.…”

Section: Discussionsupporting

confidence: 43%

PGC-1α promotes recovery after acute kidney injury during systemic inflammation in mice

Tran

Tam²,

Bardia³

et al. 2011

J. Clin. Invest.

427

489

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Sepsis-associated acute kidney injury (AKI) is a common and morbid condition that is distinguishable from typical ischemic renal injury by its paucity of tubular cell death. The mechanisms underlying renal dysfunction in individuals with sepsis-associated AKI are therefore less clear. Here we have shown that endotoxemia reduces oxygen delivery to the kidney, without changing tissue oxygen levels, suggesting reduced oxygen consumption by the kidney cells. Tubular mitochondria were swollen, and their function was impaired. Expression profiling showed that oxidative phosphorylation genes were selectively suppressed during sepsis-associated AKI and reactivated when global function was normalized. PPARγ coactivator-1α (PGC-1α), a major regulator of mitochondrial biogenesis and metabolism, not only followed this pattern but was proportionally suppressed with the degree of renal impairment. Furthermore, tubular cells had reduced PGC-1α expression and oxygen consumption in response to TNF-α; however, excess PGC-1α reversed the latter effect. Both global and tubule-specific PGC-1α-knockout mice had normal basal renal function but suffered persistent injury following endotoxemia. Our results demonstrate what we believe to be a novel mechanism for sepsis-associated AKI and suggest that PGC-1α induction may be necessary for recovery from this disorder, identifying a potential new target for future therapeutic studies.

show abstract

Section: Discussionsupporting

confidence: 43%

PGC-1α promotes recovery after acute kidney injury during systemic inflammation in mice

Tran

Tam²,

Bardia³

et al. 2011

J. Clin. Invest.

427

489

View full text Add to dashboard Cite

show abstract

“…Of these articles, 52 (38.0%) showed a decreased RVR [25, 28, 30, 31, 32, 33, 34, 36, 45, 46, 47, 51, 52, 53, 58, 62, 63, 68, 69, 70, 71, 72, 73, 74, 75, 78, 84, 85, 87, 92, 95, 98, 99, 100, 101, 109, 111, 112, 114, 115, 120, 122, 124, 125, 126, 130, 131, 135, 143, 144, 154, 155], 16 (11.7%) an unchanged RVR [23, 29, 35, 37, 60, 64, 80, 97, 106, 108, 110, 113, 116, 119, 140, 145,] and 69 (50.3%) an increased RVR [20, 21, 22, 24, 26, 27, 38, 39, 40, 41, 42, 43, 44, 48, 49, 50, 54, 55, 56, 57, 59, 61, 65, …”

Section: Resultsmentioning

confidence: 99%

“…We found 56 experiments performed in small animals [20, 24, 26, 27, 39, 42, 43, 44, 55, 57, 58, 59, 62, 63, 64, 67, 68, 72, 77, 79, 81, 82, 87, 88, 89, 90, 93, 94, 96, 97, 99, 100, 103, 104, 105, 110, 116, 120, 121, 122, 129, 132, 133, 134, 137, 138, 139, 141, 142, 143, 147, 148, 149, 150, 151] and 81 performed in large animals [21, 22, 23, 25, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 56, 60, 61, 65, 66, 69, 70, 71, 73, 74, ...…”

Section: Resultsmentioning

confidence: 99%

“…Of 59 studies using other methods [20, 29, 30, 33, 34, 36, 37, 38, 39, 40, 43, 44, 46, 47, 48, 55, 57, 59, 61, 64, 67, 68, 70, 76, 77, 79, 82, 84, 87, 88, 93, 94, 96, 97, 98, 101, 103, 104, 105, 107, 116, 120, 122, 123, 125, 129, 130, 132, 133, 134, 136, 137, 138, 139, 147, 148, 149, 150, 151], 16 (27.1%) reported a decreased RVR, 5 (8.5%) an unchanged RVR, and 38 (64.4%) an increased RVR (fig. 3; p =0.017).…”

Section: Resultsmentioning

confidence: 99%

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Renal Vascular Resistance in Sepsis

et al. 2006

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Aims: To assess changes in renal vascular resistance (RVR) in human and experimental sepsis and to identify determinants of RVR. Methods: We performed a systematic interrogation of two electronic reference libraries using specific search terms. Subjects were animals and patients involved in experimental and human studies of sepsis and septic acute renal failure, in which the RVR was assessed. We obtained all human and experimental articles reporting RVR during sepsis. We assessed the role of various factors that might influence the RVR during sepsis using statistical methods. Results: We found no human studies, in which the renal blood flow (and, therefore, the RVR) was measured with suitably accurate direct methods. Of the 137 animal studies identified, 52 reported a decreased RVR, 16 studies reported no change in RVR, and 69 studies reported an increased RVR. Consciousness of animals, duration of measurement, method of induction of sepsis, and fluid administration had no effect on the RVR. On the other hand, on univariate analysis, size of the animals (p<0.001), technique of measurement (p = 0.017), recovery after surgery (p = 0.004), and cardiac output (p <0.001) influenced the RVR. Multivariate analysis, however, showed that only cardiac output (p = 0.028) and size of the animals (p = 0.031) remained independent determinants of the RVR. Conclusions: Changes in RVR during sepsis in humans are unknown. In experimental sepsis, several factors not directly related to sepsis per se appear to influence the RVR. A high cardiac output and the use of large animals predict a decreased RVR, while a decreased cardiac output and the use of small animals predict an increased RVR.

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“…One proposed hypothesis is an increased leakiness of the proximal tubular epithelium resulting in sodium back-flow towards the tubular lumen as well as equal work for less sodium reabsorption. 52 …”

Section: The Kidney In Sepsismentioning

confidence: 99%

Review article: Organ per fusion/permeabilityrelated effects of norepinephrine and vasopressin in sepsis

Farand¹,

Hamel

Lauzier

et al. 2006

Can J Anesth/J Can Anesth

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Purpose:One invariable hallmark of severe sepsis is generalized tissue "malperfusion" and hyperpermeability secondary to microcirculatory/capillary leakage. This review focuses on direct and/or indirect influences of norepinephrine, as a standard of care, and vasopressin, as an alternative vasoactive drug, on organ and tissue perfusion/permeability in severe sepsis.Source: English and French language articles and books published between 1966 and 2005 were identified through a computerized Medline search using the terms "sepsis, permeability, norepinephrine and vasopressin". Relevant publications were retrieved and scanned for additional sources. Principal findings:There are few randomized clinical trials comparing different vasopressors in sepsis; most available literature consists of clinical reports, animal experiments and occasional reviews. Based on the best current evidence from these sources, we describe the status of major organ perfusion/ permeability in sepsis (i.e., the lung, the kidney, the heart, the intestine/gut) in the context of sepsis-induced organ dysfunction/failure. Potential and differential therapeutic effects of the vasopressors norepinephrine and arginine-vasopressin, in the setting of sepsis, are identified. Conclusions:In the treatment of sepsis, arginine-vasopressin exhibits organ-specific heterogeneity in vascular responsiveness, compared to norepinephrine. While norepinephrine is a current standard of care in sepsis, arginine-vasopressin shows promise for the treatment of septic shock. Objectif

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Renal function and oxygen consumption during bacteraemia and endotoxaemia in rats

Abstract: Our data indicate that in rat models of septic shock renal failure is not caused by cortical hypoxia or a shortage of cellular energy supply.

Cited by 30 publications

References 5 publications

PGC-1α promotes recovery after acute kidney injury during systemic inflammation in mice

PGC-1α promotes recovery after acute kidney injury during systemic inflammation in mice

Renal Vascular Resistance in Sepsis

Review article: Organ per fusion/permeabilityrelated effects of norepinephrine and vasopressin in sepsis

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