Hypothermic renal perfusion during aortic surgery reduces the presence of lipocalin-2 and preserves renal extraction of dimethylarginines in rats

Yeung, Kak K.; Matignon, Claire De Gouyon; Renwarin, Lennaert; Tjon-A-Fat, Miguel R.; Teerlink, Tom; Leeuwen, Paul A. M. van; Musters, René J.P.; Wisselink, Willem; Tangelder, Geert Jan

doi:10.1152/ajprenal.00736.2010

Cited by 5 publications

(10 citation statements)

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“…This calculation corrects a possible overestimation of the fractional renal extraction [calculated as (A Ϫ V)/A ϫ 100% (37,43,53)] in cases of a low renal plasma flow (3). A positive RPCL indicates net clearance of the substance from the blood, whereas a negative RPCL indicates net release into the blood.…”

Section: Methodsmentioning

confidence: 88%

Reduced renal plasma clearance does not explain increased plasma asymmetric dimethylarginine in hypertensive subjects with mild to moderate renal insufficiency

Ronden

Houben

Teerlink

et al. 2012

American Journal of Physiology-Renal Physiology

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PW, Kroon AA. Reduced renal plasma clearance does not explain increased plasma asymmetric dimethylarginine in hypertensive subjects with mild to moderate renal insufficiency. Am J Physiol Renal Physiol 303: F149 -F156, 2012. First published May 2, 2012 doi:10.1152/ajprenal.00045.2012.-Plasma concentrations of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) increase already in the early stages of renal insufficiency. There is no agreement as to whether reduced renal plasma clearance (RPCL) contributes to this increase. Therefore, we investigated the relationship between estimated glomerular filtration rate (eGFR), RPCL, and plasma ADMA and SDMA in essential hypertensive patients with mild to moderate renal insufficiency. In 171 patients who underwent renal angiography, we drew blood samples from the aorta and both renal veins and measured mean renal blood flow (MRBF) using the 133 Xe washout technique. RPCL was calculated using arteriovenous concentration differences and MRBF. After correction for potential confounders, reduced eGFR was associated with higher plasma ADMA and SDMA [standardized regression coefficient (␤) ϭ Ϫ0.22 (95% confidence intervals: Ϫ0.41, Ϫ0.04) and ␤ ϭ Ϫ0.66 (95% confidence intervals: Ϫ0.83, Ϫ0.49), respectively]. However, eGFR was not independently associated with RPCL of ADMA. Moreover, reduced RPCL of ADMA was not associated with higher plasma ADMA. Contrary to ADMA, reduced eGFR was indeed associated with lower RPCL of SDMA [␤ ϭ 0.21 (95% confidence intervals: 0.02, 0.40)]. In conclusion, our findings indicate that RPCL of ADMA is independent of renal function in hypertensive patients with mild to moderate renal insufficiency. Unlike the case for SDMA, reduced RPCL of ADMA is of minor importance for the increase in plasma ADMA in these patients, which indicates that increased plasma ADMA in this population is not a direct consequence of the kidneys failing as a plasma ADMA-regulating organ. dimethylarginines; renal function; hypertension IN PATIENTS with chronic kidney disease (CKD), the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and its structural isomer symmetric dimethylarginine (SDMA) build up in plasma even in the early stages of renal insufficiency (10,19,21). Moreover, ADMA already rises in incipient CKD. The exact mechanisms responsible for this increase of ADMA and SDMA at these early stages of CKD have not been totally clarified but are likely to involve changes in the regulation of the plasma concentration by the kidneys' renal plasma clearance (RPCL) (37,49).The kidneys play an important role in the plasma concentration regulation of ADMA and SDMA. By measuring arteriovenous concentration differences, a previous study (37) demonstrated that the kidneys clear substantial amounts of ADMA and SDMA from the circulation. Furthermore, both dimethylarginines are excreted in the urine in amounts, which are dependent on the glomerular filtration rate (GFR) (2,30,31,49). However, the main...

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Section: Methodsmentioning

confidence: 88%

Reduced renal plasma clearance does not explain increased plasma asymmetric dimethylarginine in hypertensive subjects with mild to moderate renal insufficiency

Ronden

Houben

Teerlink

et al. 2012

American Journal of Physiology-Renal Physiology

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“…The present experimental protocol was based on previously published studies in which JAA repair was simulated in a rat model. 22,23 Animal surgery and care were performed according to established guidelines and approved by the Animal Ethical Commission VU University Medical Centre, Amsterdam, the Netherlands (protocol number FYS 07e08). Four groups of seven adult male Wistar rats were created (350 g; Harlan), every day a rat from another group was operated on sequentially.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…1). 22,23 The rats received6 mL saline intravenously, to compensate for the volume the perfused groups received by renal cooling.…”

Section: Juxtarenal Aortic Aneurysm Repair Simulation Groupsmentioning

confidence: 99%

“…22 Cold renal perfusion during the suprarenal clamping period could reduce kidney damage and preserve the bioavailability of NO. 23 Furthermore, renal tubular damage was reduced and renal extraction of dimethylarginines was preserved, leading to lower oxidative stress in the kidneys. 23 The same effect was also demonstrated in single centre observational cohort studies, as cold renal perfusion reduced the incidence of AKI after elective open JAA repair.…”

Section: Introductionmentioning

confidence: 99%

“…23 Furthermore, renal tubular damage was reduced and renal extraction of dimethylarginines was preserved, leading to lower oxidative stress in the kidneys. 23 The same effect was also demonstrated in single centre observational cohort studies, as cold renal perfusion reduced the incidence of AKI after elective open JAA repair. Interestingly, renal cooling during JAA repair has a protective effect on the development of MOF after acute JAA repair.…”

Section: Introductionmentioning

confidence: 99%

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Cold Renal Perfusion During Simulation of Juxtarenal Aortic Aneurysm Repair Reduces Systemic Oxidative Stress and Sigmoid Damage in Rats

Schaik

Jongkind

Lindhout

et al. 2019

European Journal of Vascular and Endovascular Surgery

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WHAT THIS PAPER ADDS Complications of juxtarenal aortic aneurysm repair include renal ischaemia reperfusion injury and post-operative colonic ischaemia. Renal ischaemia reperfusion injury results in the production of reactive oxygen species during oxidative stress. In the present study renal cooling preserved renal function. Above all, renal cooling was able to reduce the detrimental remote effects on sigmoid integrity of renal ischaemia reperfusion caused by suprarenal clamping; by preserving microcirculatory flow, attenuating circulating leukocyte ROS production, and decreasing leukocyte infiltration in the sigmoid. Objectives: Juxtarenal aortic surgery induces renal ischaemia reperfusion, which contributes to systemic inflammatory tissue injury and remote organ damage. Renal cooling during suprarenal cross clamping has been shown to reduce renal damage. It is hypothesised that renal cooling during suprarenal cross clamping also has systemic effects and could decrease damage to other organs, like the sigmoid colon. Methods: Open juxtarenal aortic aneurysm repair was simulated in 28 male Wistar rats with suprarenal cross clamping for 45 min, followed by 20 min of infrarenal aortic clamping. Four groups were created: sham, no, warm (37 C saline), and cold (4 C saline) renal perfusion during suprarenal cross clamping. Primary outcomes were renal damage and sigmoid damage. To assess renal damage, procedure completion serum creatinine rises were measured. Peri-operative microcirculatory flow ratios were determined in the sigmoid using laser Doppler flux. Semi-quantitative immunofluorescence microscopy was used to measure alterations in systemic inflammation parameters, including reactive oxygen species (ROS) production in circulating leukocytes and leukocyte infiltration in the sigmoid. Sigmoid damage was assessed using digestive enzyme (intestinal fatty acid binding protein-I-FABP) leakage, a marker of intestinal integrity. Results: Suprarenal cross clamping caused deterioration of all systemic parameters. Only cold renal perfusion protected against serum creatinine rise: 0.45 mg/dL without renal perfusion, 0.33 mg/dL, and 0.14 mg/dL (p ¼ .009) with warm and cold perfusion, respectively. Microcirculation in the sigmoid was attenuated with warm (p ¼ .002) and cold renal perfusion (p ¼ .002). A smaller increase of ROS production (p ¼ .034) was seen only after cold perfusion, while leukocyte infiltration in the sigmoid colon decreased after warm (p ¼ .006) and cold perfusion (p ¼ .018). Finally, digestive enzyme leakage increased more without (1.5AU) than with warm (1.3AU; p ¼ .007) and cold renal perfusion (1.2AU; p ¼ .002). Conclusions: Renal ischaemia/reperfusion injury after suprarenal cross clamping decreased microcirculatory flow, increased systemic ROS production, leukocyte infiltration, and I-FABP leakage in the sigmoid colon. Cold renal perfusion was superior to warm perfusion and reduced renal damage and had beneficial systemic effects, reducing sigmoid damage in this experimental study.

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Organ protection during aortic cross-clamping

Yeung

Groeneveld

Lu³

et al. 2016

Best Practice & Research Clinical Anaesthesiology

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Hypothermic renal perfusion during aortic surgery reduces the presence of lipocalin-2 and preserves renal extraction of dimethylarginines in rats

Cited by 5 publications

References 47 publications

Reduced renal plasma clearance does not explain increased plasma asymmetric dimethylarginine in hypertensive subjects with mild to moderate renal insufficiency

Reduced renal plasma clearance does not explain increased plasma asymmetric dimethylarginine in hypertensive subjects with mild to moderate renal insufficiency

Cold Renal Perfusion During Simulation of Juxtarenal Aortic Aneurysm Repair Reduces Systemic Oxidative Stress and Sigmoid Damage in Rats

Organ protection during aortic cross-clamping

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