scholarly journals Preservation of renal endothelial integrity and reduction of renal edema by aprotinin does not preserve renal perfusion and function following experimental cardiopulmonary bypass

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Nicole A. M. Dekker ◽  
Anoek L. I. van Leeuwen ◽  
Matijs van Meurs ◽  
Jill Moser ◽  
Jeannette E. Pankras ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Renal Injury ◽  
Weight Ratio ◽  
Kidney Injury ◽  
Dry Weight ◽  
Renal Perfusion ◽  
Plasma Creatinine ◽  
Microcirculatory Perfusion ◽  
Neutrophil Influx ◽  
Endothelial Integrity

Abstract Background Acute kidney injury is a severe complication following cardiopulmonary bypass (CPB) and is associated with capillary leakage and microcirculatory perfusion disturbances. CPB-induced thrombin release results in capillary hyperpermeability via activation of protease-activated receptor 1 (PAR1). We investigated whether aprotinin, which is thought to prevent thrombin from activating PAR1, preserves renal endothelial structure, reduces renal edema and preserves renal perfusion and reduces renal injury following CPB. Methods Rats were subjected to CPB after treatment with 33.000 KIU/kg aprotinin (n = 15) or PBS (n = 15) as control. A secondary dose of 33.000 KIU/kg aprotinin was given 60 min after initiation of CPB. Cremaster and renal microcirculatory perfusion were assessed using intravital microscopy and contrast echography before CPB and 10 and 60 min after weaning from CPB. Renal edema was determined by wet/dry weight ratio and renal endothelial structure by electron microscopy. Renal PAR1 gene and protein expression and markers of renal injury were determined. Results CPB reduced cremaster microcirculatory perfusion by 2.5-fold (15 (10–16) to 6 (2–10) perfused microvessels, p < 0.0001) and renal perfusion by 1.6-fold (202 (67–599) to 129 (31–292) au/sec, p = 0.03) in control animals. Both did not restore 60 min post-CPB. This was paralleled by increased plasma creatinine (p < 0.01), neutrophil gelatinase-associated lipocalin (NGAL; p = 0.003) and kidney injury molecule-1 (KIM-1; p < 0.01). Aprotinin treatment preserved cremaster microcirculatory perfusion following CPB (12 (7–15) vs. 6 (2–10) perfused microvessels, p = 0.002), but not renal perfusion (96 (35–313) vs. 129 (31–292) au/s, p > 0.9) compared to untreated rats. Aprotinin treatment reduced endothelial gap formation (0.5 ± 0.5 vs. 3.1 ± 1.4 gaps, p < 0.0001), kidney wet/dry weight ratio (4.6 ± 0.2 vs. 4.4 ± 0.2, p = 0.046), and fluid requirements (3.9 ± 3.3 vs. 7.5 ± 3.0 ml, p = 0.006) compared to untreated rats. In addition, aprotinin treatment reduced tubulointerstitial neutrophil influx by 1.7-fold compared to untreated rats (30.7 ± 22.1 vs. 53.2 ± 17.2 neutrophil influx/section, p = 0.009). No differences were observed in renal PAR1 expression and plasma creatinine, NGAL or KIM-1 between groups. Conclusions Aprotinin did not improve renal perfusion nor reduce renal injury during the first hour following experimental CPB despite preservation of renal endothelial integrity and reduction of renal edema.

scholarly journals Renal hemodynamics and oxygenation during experimental cardiopulmonary bypass in sheep under total intravenous anesthesia

2020 ◽  
Vol 318 (2) ◽  
pp. R206-R213 ◽  
Author(s):  
Roger G. Evans ◽  
Naoya Iguchi ◽  
Andrew D. Cochrane ◽  
Bruno Marino ◽  
Sally G. Hood ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiopulmonary Bypass ◽  
Renal Blood Flow ◽  
Kidney Injury ◽  
Conscious State ◽  
Renal Perfusion ◽  
Total Intravenous Anesthesia ◽  
Intravenous Anesthesia ◽  
Isoflurane Anesthesia ◽  
Conscious Sheep

Renal medullary hypoxia may contribute to the pathophysiology of acute kidney injury, including that associated with cardiac surgery requiring cardiopulmonary bypass (CPB). When performed under volatile (isoflurane) anesthesia in sheep, CPB causes renal medullary hypoxia. There is evidence that total intravenous anesthesia (TIVA) may preserve renal perfusion and renal oxygen delivery better than volatile anesthesia. Therefore, we assessed the effects of CPB on renal perfusion and oxygenation in sheep under propofol/fentanyl-based TIVA. Sheep ( n = 5) were chronically instrumented for measurement of whole renal blood flow and cortical and medullary perfusion and oxygenation. Five days later, these variables were monitored under TIVA using propofol and fentanyl and then on CPB at a pump flow of 80 mL·kg−1·min−1 and target mean arterial pressure of 70 mmHg. Under anesthesia, before CPB, renal blood flow was preserved under TIVA (mean difference ± SD from conscious state: −16 ± 14%). However, during CPB renal blood flow was reduced (−55 ± 13%) and renal medullary tissue became hypoxic (−20 ± 13 mmHg versus conscious sheep). We conclude that renal perfusion and medullary oxygenation are well preserved during TIVA before CPB. However, CPB under TIVA leads to renal medullary hypoxia, of a similar magnitude to that we observed previously under volatile (isoflurane) anesthesia. Thus use of propofol/fentanyl-based TIVA may not be a useful strategy to avoid renal medullary hypoxia during CPB.

scholarly journals Protective role of testosterone in ischemia-reperfusion-induced acute kidney injury

2013 ◽  
Vol 304 (11) ◽  
pp. R951-R958 ◽  
Author(s):  
Andrea Soljancic ◽  
Arnaldo Lopez Ruiz ◽  
Kiran Chandrashekar ◽  
Rodrigo Maranon ◽  
Ruisheng Liu ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
Renal Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Serum Testosterone ◽  
Protective Role ◽  
Male Rats ◽  
Plasma Creatinine ◽  
Acute Ischemia ◽  
Kidney Injury Molecule 1

Men are at greater risk for renal injury and dysfunction after acute ischemia-reperfusion (I/R) than are women. Studies in animals suggest that the reason for the sex difference in renal injury and dysfunction after I/R is the protective effect of estrogens in females. However, a reduction in testosterone in men is thought to play an important role in mediating cardiovascular and renal disease, in general. In the present study, we tested the hypothesis that I/R of the kidney reduces serum testosterone, and that contributes to renal dysfunction and injury. Male rats that were subjected to renal ischemia of 40 min followed by reperfusion had a 90% reduction in serum testosterone by 3 h after reperfusion that remained at 24 h. Acute infusion of testosterone 3 h after reperfusion attenuated the increase in plasma creatinine and urinary kidney injury molecule-1 (KIM-1) at 24 h, prevented the reduction in outer medullary blood flow, and attenuated the increase in intrarenal TNF-α and the decrease in intrarenal VEGF at 48 h. Castration of males caused greater increases in plasma creatinine and KIM-1 at 24 h than in intact males with renal I/R, and treatment with anastrozole, an aromatase inhibitor, plus testosterone almost normalized plasma creatinine and KIM-1 in rats with renal I/R. These data show that renal I/R is associated with sustained reductions in testosterone, that testosterone repletion protects the kidney, whereas castration promotes renal dysfunction and injury, and that the testosterone-mediated protection is not conferred by conversion to estradiol.

scholarly journals Impaired microcirculatory perfusion in a rat model of cardiopulmonary bypass: the role of hemodilution

2016 ◽  
Vol 310 (5) ◽  
pp. H550-H558 ◽  
Author(s):  
Nick J. Koning ◽  
Fellery de Lange ◽  
Alexander B. A. Vonk ◽  
Yunus Ahmed ◽  
Charissa E. van den Brom ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Adhesion Molecule ◽  
Rat Model ◽  
Renal Injury ◽  
Tissue Injury ◽  
Multiple Time ◽  
Adhesion Molecule Expression ◽  
Microcirculatory Perfusion ◽  
Endothelial Adhesion Molecule ◽  
Sham Procedure

Although hemodilution is attributed as the main cause of microcirculatory impairment during cardiopulmonary bypass (CPB), this relationship has never been investigated. We investigated the distinct effects of hemodilution with or without CPB on microvascular perfusion and subsequent renal tissue injury in a rat model. Male Wistar rats (375–425 g) were anesthetized, prepared for cremaster muscle intravital microscopy, and subjected to CPB ( n = 9), hemodilution alone ( n = 9), or a sham procedure ( n = 6). Microcirculatory recordings were performed at multiple time points and analyzed for perfusion characteristics. Kidney and lung tissue were investigated for mRNA expression for genes regulating inflammation and endothelial adhesion molecule expression. Renal injury was assessed with immunohistochemistry. Hematocrit levels dropped to 0.24 ± 0.03 l/l and 0.22 ± 0.02 l/l after onset of hemodilution with or without CPB. Microcirculatory perfusion remained unaltered in sham rats. Hemodilution alone induced a 13% decrease in perfused capillaries, after which recovery was observed. Onset of CPB reduced the perfused capillaries by 40% (9.2 ± 0.9 to 5.5 ± 1.5 perfused capillaries per microscope field; P < 0.001), and this reduction persisted throughout the experiment. Endothelial and inflammatory activation and renal histological injury were increased after CPB compared with hemodilution or sham procedure. Hemodilution leads to minor and transient disturbances in microcirculatory perfusion, which cannot fully explain impaired microcirculation following cardiopulmonary bypass. CPB led to increased renal injury and endothelial adhesion molecule expression in the kidney and lung compared with hemodilution. Our findings suggest that microcirculatory impairment during CPB may play a role in the development of kidney injury.

scholarly journals Urinary Mitochondrial DNA Identifies Renal Dysfunction and Mitochondrial Damage in Sepsis-Induced Acute Kidney Injury

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Qiongyuan Hu ◽  
Jianan Ren ◽  
Huajian Ren ◽  
Jie Wu ◽  
Xiuwen Wu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Renal Dysfunction ◽  
Renal Injury ◽  
Cecal Ligation ◽  
Surrogate Marker ◽  
Kidney Injury ◽  
Plasma Creatinine ◽  
Acute Renal Dysfunction

Background. Recent animal studies have shown that mitochondrial dysfunction initiates and accelerates renal injury in sepsis, but its role in sepsis remains unknown. Mitochondrial stress or dying cells can lead to fragmentation of the mitochondrial genome, which is considered a surrogate marker of mitochondrial dysfunction. Therefore, we evaluated the efficiency of urinary mitochondrial DNA (UmtDNA) as a marker of renal dysfunction during sepsis-induced acute kidney injury (AKI). Methods. We isolated DNA from plasma and urine of patients. mtDNA levels were quantified by quantitative PCR. Sepsis patients were divided into no AKI, mild AKI, and severe AKI groups according to RIFLE criteria. Additionally, cecal ligation and puncture (CLP) was established in rats to evaluate the association between UmtDNA and mitochondrial function. Results. A total of 52 (49.5%) developed AKI among enrolled sepsis patients. Increased systemic mtDNA did not correlate with systemic inflammation or acute renal dysfunction in sepsis patients, while AKI did not have an additional effect on circulating mtDNA levels. In contrast, UmtDNA was significantly enriched in severe AKI patients compared with that in the mild AKI or no AKI group, positively correlated with plasma creatinine, urinary neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1, and inversely with the estimated glomerular filtration rate. Additionally, UmtDNA increased in rats following CLP-induced sepsis. UmtDNA was predictive of AKI development and correlated with plasma creatinine and blood urea nitrogen in the rat sepsis model. Finally, the UmtDNA level was inversely correlated with the cortical mtDNA copy number and relative expression of mitochondrial gene in the kidney. Conclusion. An elevated UmtDNA level correlates with mitochondrial dysfunction and renal injury in sepsis patients, indicating renal mitochondrial injury induced by sepsis. Therefore, UmtDNA may be regarded as a valuable biomarker for the occurrence of AKI and the development of mitochondria-targeted therapies following sepsis-induced AKI.

Low-dose carvedilol protects against acute septic renal injury in rats during the early and late phases

2015 ◽  
Vol 93 (6) ◽  
pp. 443-450 ◽  
Author(s):  
Hala Salah Abdel kawy
Keyword(s):  
Renal Injury ◽  
Cecal Ligation ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Kidney Injury ◽  
Serum Levels ◽  
Renal Perfusion ◽  
Protein Carbonyls ◽  
Necrosis Factor Alpha ◽  
Inflammatory Parameters ◽  
The Impact

Recent findings from septic acute renal injury studies have implicated the mitochondrion as an important factor in kidney injury, and that increased sympathetic nerve activity may contribute to the induction of organ failure. This study investigated the impact of a nondepressor dose of carvedilol, which is a beta-adrenoreceptor antagonist with antioxidant activity, on septic renal injury induced in rats with cecal ligation and puncture (CLP). Three groups of rats were studied. The first group was the sham-operated control. The other 2 groups of rats underwent CLP, and were administered either the vehicle or carvedilol (2.0 mg/kg body mass, by intraperitoneal (i.p.) injection, daily for 2 days as well as 30 min prior to CLP). Kidney function, inflammatory parameters, mitochondrial function, and renal perfusion pressure (RPP) were investigated at 6 and 18 h after CLP. Carvedilol did not significantly induce hypotension, and it significantly improved RPP and renal dysfunction induced with CLP, together with significant reductions in serum levels of interleukin 6 and tumor necrosis factor-alpha. Septic kidney injury mediated increased levels of malondialdehyde and protein carbonyls. Carvedilol also attenuated the decrease in kidney mitochondrial glutathione and nicotinamide adenine dinucleotide phosphate dehydrogenase. Further, intracellular renal edema and inflammation induced with CLP were reduced with carvedilol. These findings suggest renoprotective effects of carvedilol in sepsis.

scholarly journals Mild Acute Kidney Injury after Noncardiac Surgery Is Associated with Long-term Renal Dysfunction

2020 ◽  
Vol 132 (5) ◽  
pp. 1053-1061 ◽  
Author(s):  
Alparslan Turan ◽  
Barak Cohen ◽  
Janet Adegboye ◽  
Natalya Makarova ◽  
Liu Liu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Dysfunction ◽  
Renal Injury ◽  
Cohort Analysis ◽  
Cleveland Clinic ◽  
Kidney Injury ◽  
Noncardiac Surgery ◽  
Stage I ◽  
Plasma Creatinine

Abstract Background Perioperative acute kidney injury is common. However, it is unclear whether this merely represents a transient increase in creatinine or has prognostic value. Therefore, the long-term clinical importance of mild postoperative acute kidney injury remains unclear. This study assessed whether adults who do and do not experience mild kidney injury after noncardiac surgery are at similar risk for long-term renal injury. Methods This study is a retrospective cohort analysis of adults having noncardiac surgery at the Cleveland Clinic who had preoperative, postoperative, and long-term (1 to 2 yr after surgery) plasma creatinine measurements. The exposure (postoperative kidney injury) and outcome (long-term renal injury) were defined and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) initiative criteria. The primary analysis was for lack of association between postoperative kidney injury (stage I vs. no injury) and long-term renal injury. Results Among 15,621 patients analyzed, 3% had postoperative stage I kidney injury. Long-term renal outcomes were not similar in patients with and without postoperative stage I injury. Specifically, about 26% of patients with stage I postoperative kidney injury still had mild injury 1 to 2 yr later, and 11% had even more severe injury. A full third (37%) of patients with stage I kidney injury therefore had renal injury 1 to 2 yr after surgery. Patients with postoperative stage I injury had an estimated 2.4 times higher odds of having long-term renal dysfunction (KDIGO stage I, II, or III) compared with patients without postoperative kidney injury (odds ratio [95% CI] of 2.4 [2.0 to 3.0]) after adjustment for potential confounding factors. Conclusions In adults recovering from noncardiac surgery, even small postoperative increases in plasma creatinine, corresponding to stage I kidney injury, are associated with renal dysfunction 1 to 2 yr after surgery. Even mild postoperative renal injury should therefore be considered a clinically important perioperative outcome. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

scholarly journals The effect of targeting Tie2 on hemorrhagic shock-induced renal perfusion disturbances in rats

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Anoek L. I. van Leeuwen ◽  
Nicole A. M. Dekker ◽  
Paul Van Slyke ◽  
Esther de Groot ◽  
Marc G. Vervloet ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Fluid Resuscitation ◽  
Renal Injury ◽  
Kidney Injury ◽  
Renal Perfusion ◽  
Vascular Leakage ◽  
Edema Formation ◽  
Baseline Values ◽  
Angiopoietin 2 ◽  
And Function

Abstract Background Hemorrhagic shock is associated with acute kidney injury and increased mortality. Targeting the endothelial angiopoietin/Tie2 system, which regulates endothelial permeability, previously reduced hemorrhagic shock-induced vascular leakage. We hypothesized that as a consequence of vascular leakage, renal perfusion and function is impaired and that activating Tie2 restores renal perfusion and function. Methods Rats underwent 1 h of hemorrhagic shock and were treated with either vasculotide or PBS as control, followed by fluid resuscitation for 4 h. Microcirculatory perfusion was measured in the renal cortex and cremaster muscle using contrast echography and intravital microscopy, respectively. Changes in the angiopoietin/Tie2 system and renal injury markers were measured in plasma and on protein and mRNA level in renal tissue. Renal edema formation was determined by wet/dry weight ratios and renal structure by histological analysis. Results Hemorrhagic shock significantly decreased renal perfusion (240 ± 138 to 51 ± 40, p < 0.0001) and cremaster perfusion (12 ± 2 to 5 ± 2 perfused vessels, p < 0.0001) compared to baseline values. Fluid resuscitation partially restored both perfusion parameters, but both remained below baseline values (renal perfusion 120 ± 58, p = 0.08, cremaster perfusion 7 ± 2 perfused vessels, p < 0.0001 compared to baseline). Hemorrhagic shock increased circulating angiopoietin-1 (p < 0.0001), angiopoietin-2 (p < 0.0001) and soluble Tie2 (p = 0.05), of which angiopoietin-2 elevation was associated with renal edema formation (r = 0.81, p < 0.0001). Hemorrhagic shock induced renal injury, as assessed by increased levels of plasma neutrophil gelatinase-associated lipocalin (NGAL: p < 0.05), kidney injury marker-1 (KIM-1; p < 0.01) and creatinine (p < 0.05). Vasculotide did not improve renal perfusion (p > 0.9 at all time points) or reduce renal injury (NGAL p = 0.26, KIM-1 p = 0.78, creatinine p > 0.9, renal edema p = 0.08), but temporarily improved cremaster perfusion at 3 h following start of fluid resuscitation compared to untreated rats (resuscitation + 3 h: 11 ± 3 vs 8 ± 3 perfused vessels, p < 0.05). Conclusion Hemorrhagic shock-induced renal impairment cannot be restored by standard fluid resuscitation, nor by activation of Tie2. Future treatment strategies should focus on reducing angiopoietin-2 levels or on activating Tie2 via an alternative strategy.

Urine Output during Cardiopulmonary Bypass Predicts Acute Kidney Injury after Coronary Artery Bypass Grafting

2016 ◽  
Vol 19 (6) ◽  
pp. 289 ◽  
Author(s):  
Mehmet Yilmaz ◽  
Rezan Aksoy ◽  
Vildan Kilic Yilmaz ◽  
Canan Balci ◽  
Cagri Duzyol ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cardiopulmonary Bypass ◽  
Coronary Artery ◽  
Coronary Artery Bypass Grafting ◽  
Coronary Artery Bypass ◽  
Urine Output ◽  
Artery Bypass ◽  
Kidney Injury ◽  
Urinary Output ◽  
Bypass Grafting

Objective: This study evaluated the relationship between the amount of urinary output during cardiopulmonary bypass and acute kidney injury in the postoperative period of coronary artery bypass grafting.Methods: Two hundred patients with normal preoperative serum creatinine levels, operated on with isolated CABG between 2012-2014 were investigated retrospectively. The RIFLE (Risk, injury, failure, loss of function, and end-stage renal disease) risk scores were calculated for each patient in the third postoperative day. Patients were distributed into two groups in relation to the presence of acute kidney injury or not and these two groups were compared.Results: The urinary output (mL/kg/hour) during cardiopulmonary bypass in the acute kidney injury negative group was significantly higher than in the acute kidney injury positive group (P = .022). In case of a urinary output value 3.70 and lower to predict acute kidney injury positivity, sensitivity was detected as 71.43%. Results of the analysis for urinary output predict positivity of acute kidney injury.Conclusion: We suggest that urine output during cardiopulmonary bypass is a significant criteria that could predict acute kidney injury following coronary artery bypass grafting with cardiopulmonary bypass. Attempts to increase the urine output during cardiopulmonary bypass could help to maintain the renal functions during and after surgery.

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