Decrease In Renal Blood Flow Research Articles

Pathophysiological differences between multifocal fibromuscular dysplasia and atherosclerotic renal artery stenosis.

Fibromuscular dysplasia (FMD) and atherosclerotic renal artery stenosis (ARAS) are the most common causes of renovascular hypertension. So far, FMD is believed to cause hypertension via similar mechanisms as in ARAS, that is, a decrease in renal blood flow, which subsequently leads to increased renin secretion. However, given the differences in the blood pressure (BP)-lowering effect of revascularization between patients with ARAS and FMD, we questioned whether this is true. We measured renal blood flow (Xenon washout method) and renin secretion per kidney and their relationship to BP in a cohort of 64 patients with multifocal FMD and 110 patients with ARAS (off medication, prior to revascularization). We found that renal blood flow is significantly higher in FMD as compared with ARAS. In patients with unilateral ARAS, renin secretion was increased in the affected kidney as compared with the unaffected kidney. This lateralization in renin secretion, however, was not found in unilateral FMD. After correction for differences in baseline characteristics, we found that systemic renin levels and local renin secretion was lower in FMD as compared with ARAS. Moreover, the relationship between BP and renin secretion in FMD was inverse to that in ARAS. These findings argue against the hypothesis that FMD induces hypertension via similar pathophysiological mechanism as in ARAS.

Susceptibility to Pressure‐induced Renal Injury in DOCA‐salt vs. Angiotensin II Hypertensive Rats

Deoxycorticosterone acetate (DOCA) plus high salt diet feeding in rats is a low‐renin model of hypertension commonly used to investigate the pathogenesis of renal disease. Previous studies have reported that DOCA‐salt‐induced hypertension impairs renal blood flow (RBF) autoregulation; however, the susceptibility to blood pressure (BP)‐induced renal injury has not been determined. The goal of this study was to compare the BP‐renal injury and BP‐RBF relationships between DOCA‐salt and ANG II hypertensive rats.BP (radiotelemetry), proteinuria and renal injury were measured in male Sprague‐Dawley (SD) rats (Charles River) administered DOCA (3.3 mg/day s.c.) plus 1% NaCl + 0.2% KCl in the drinking water (n=15) and in rats administered ANG II (500 ng/kg/min s.c.) (n=12) for 6 weeks. The average 6‐week systolic BP was greater (P<0.05) in rats administered ANG II vs. DOCA‐salt (175±4 vs. 165±5 mmHg); however, proteinuria was not significantly different in ANG II vs. DOCA‐salt (60±11 vs. 86±15 mg/day) groups. A similar and modest level of glomerulosclerosis (GS) was seen in both ANG II (6±1%) and DOCA‐salt groups (7±3%); however, the slope of relationship between GS and BP was greater (P<0.05) in rats administered DOCA‐salt vs. ANG II (0.54 vs. 0.15 Δ%GS/ΔmmHg systolic BP). These data indicate that the susceptibility to BP‐induced renal injury is greater in DOCA‐salt vs. ANG II‐infused hypertensive rats.BP and RBF were measured in conscious chronically instrumented rats for 2–3 hours/day during 2–3 baseline recordings and over days 3–7 of DOCA‐salt (n=5) or ANG II (n=9) administration. We also assessed glomerular filtration rate (GFR) before and during DOCA‐salt administration. Robust and significant differences were observed in the average BP, RBF and renal vascular resistance (RVR) responses between groups. ANG II administration led to a 50% increase in mean BP (P<0.05), 100% increase in RVR (P<0.05) and 25% decrease in RBF (P<0.05). In contrast, while DOCA‐salt led to a more modest 11% increase in mean BP (P<0.05), RVR decreased by 25% (P<0.05) resulting in a 46% increase in RBF (P<0.05). The administration of DOCA‐salt did not significantly alter GFR. RBF autoregulation (changes in RBF during spontaneous changes in BP of 5 mmHg or greater) was assessed from the BP‐RBF recordings in conscious rats using recently developed novel methodologies. No effects of DOCA‐salt on RBF autoregulation were observed. In contrast, ANG II strengthened the RBF autoregulatory response, particularly within the first second following a change in BP of 5 mmHg or more.In summary, the reduced renal vascular tone in DOCA‐salt hypertensive rats may be contributing to its greater susceptibility to BP‐induced renal injury as compared to ANG II hypertensive rats. The augmentation of RBF autoregulatory responses by ANG II may also be contributing to the reduced susceptibility to BP‐induced renal injury in this model.Support or Funding InformationVeterans Administration, NIH

The Role of β-Adrenergic Overstimulation in the Early Stages of Renal Injury

Background/Aims: To assess the possible contribution of the β-adrenergic overstimulation in early stages of renal injury, the present study evaluated, in rats, the effects of the β-adrenoceptor agonist isoproterenol (ISO) on renal function and morphology, as well as the renal mRNA and protein expression of the NADPH oxidase isoform 4 (Nox 4) and subunit p22^phox, endoplasmic reticulum (ER) stress, pro-inflammatory, pro-apoptotic and renin-angiotensin system (RAS) components. Methods: Wistar rats received ISO (0.3 mg.kg^-1.day^-1 s.c.) or vehicle (control) for eight days. At the end of the treatment, food and water intake, urine output and body weight gain were evaluated and renal function studies were performed. Renal tissue was used for the morphological, quantitative PCR and immunohistochemical studies. Results: ISO did not change metabolic parameters or urine output. However it induced a decrease in renal blood flow and an increase in the filtration fraction. These changes were accompanied by increased cortical mRNA and protein expression for the renal oxidative stress components including Nox 4 and p22^phox; ER stress, pro-inflamatory, pro-apoptotic as well as RAS components. ISO also induced a significant increase in medullar renin protein expression. Conclusion: These findings support relevant information regarding the contribution of specific β-adrenergic hyperactivity in early stage of renal injury, indicating the reactive oxygen species, ER stress and intrarenal RAS as important factors in this process.

Clinical practice guideline for drug-induced kidney injury in Japan 2016: digest version.

The definition of DKI is a new onset of kidney injury or the worsening of an existing kidney injury due to drug administration. DKI can be classified based on the mechanism of pathogenesis, as well as on the damaged segment of the kidney. The classification based on the mechanism of pathogenesis is as follows: (1) toxic kidney injury (direct toxicity); (2) acute interstitial nephritis (AIN) due to allergic mechanism (hypersensitivity and direct toxicity); (3) indirect toxicity, such as electrolyte abnormalities and decrease of renal blood flow; and (4) obstruction of urinary tract. The classification based on the damaged segment of kidney is as follows: (1) glomerular injury; (2) tubular injury; (3) interstitial injury; and (4) vascular injury. The criteria for diagnosis are as follows: (1) new onset of kidney injury after the start of the administration of the candidate agent and (2) improvement or stoppage of the progression of the kidney injury after the cessation of the candidate agent, and all other causes can be ruled out. The cornerstone of treatment is the identification and cessation of the candidate agent as soon as possible.

Effects of Platelet-Rich Plasma (PRP) on a Model of Renal Ischemia-Reperfusion in Rats.

Renal ischemia-reperfusion injury is a major cause of acute renal failure, causing renal cell death, a permanent decrease of renal blood flow, organ dysfunction and chronic kidney disease. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, and therefore able to promote tissue regeneration and angiogenesis. This product has proven its efficacy in multiple studies, but has not yet been tested on kidney tissue. The aim of this work is to evaluate whether the application of PRP to rat kidneys undergoing ischemia-reperfusion reduces mid-term kidney damage. A total of 30 monorrenal Sprague-Dawley male rats underwent renal ischemia-reperfusion for 45 minutes. During ischemia, PRP (PRP Group, n = 15) or saline solution (SALINE Group, n = 15) was administered by subcapsular renal injection. Control kidneys were the contralateral organs removed immediately before the start of ischemia in the remaining kidneys. Survival, body weight, renal blood flow on Doppler ultrasound, kidney weight, kidney volume, blood biochemistry and histopathology were determined for all subjects and kidneys, as applicable. Correlations between these variables were searched for. The PRP Group showed significantly worse kidney blood flow (p = 0.045) and more histopathological damage (p<0.0001). Correlations were found between body weight, kidney volume, kidney weight, renal blood flow, histology, and serum levels of creatinine and urea. Our study provides the first evidence that treatment with PRP results in the deterioration of the kidney’s response to ischemia-reperfusion injury.

The Effect Of An Active Versus Inactive Lifestyle On Renal Response To Exercise-induced Dehydration

PURPOSE: Exercise by itself as well as exercise-induced dehydration cause a decrease in renal blood flow and an increase in glomerular permeability, leading to a decrement in renal function and temporarily renal damage. An active lifestyle may precondition the kidneys, resulting in attenuated decrease in kidney function and a reduction in kidney damage in response to exercise and dehydration determined as body weight loss. Therefore, we examined the differences in renal responses to exercise-induced dehydration between healthy young men with a physically active versus inactive lifestyle. METHODS: A total of 12 active and 6 inactive healthy male participants (23±3 years, 23.9±3.6 kg/m2, eGFR: 111.0±12.5 mL/min) were included, based on a physical activity questionnaire. Participants performed an incremental exercise test to determine physical fitness and maximum heart rate (HRmax). On a separate day, a submaximal exercise test was performed on 80% of the individual HRmax, until 3% dehydration. Blood and urine samples were taken pre- and post-exercise to assess renal function (estimated glomerular filtration ratio; eGFR) and renal damage (urinary albumin). RESULTS: Maximum oxygen uptake (VO2max) was higher in the active (59.7±8.6 mL/min/kg) compared to the inactive group (49.1±7.3 mL/min/kg; p=0.018). All subjects cycled on a comparable exercise intensity (79±2% HRmax), resulting in a body mass loss of 3.2±0.7% and 2.5±0.4% for the active and inactive group, respectively (p=0.013). After exercise, a significant decrease in eGFR was found for the active (17.4±10.2 mL/min; p=0.007) and inactive group (21.7±17.8 mL/min; p=0.05), which did not differ between groups (p=0.60). Moreover, 33.3% of the active subjects and 50% of the inactive subjects had a post-exercise eGFR<90 mL/min, which indicates a decrease in renal function. Furthermore, we found a significant increase in urinary albumin concentration in the active (24.6±30.9 mg/L; p=0.011) and inactive group (33.6±27.5 mg/L; p=0.016), which did not differ between groups (p=0.55). CONCLUSION: In short, exercise induces a decrease in renal function and an increase in urinary albumin concentration, suggesting temporary renal damage of the glomerulus or proximal tubulus. However, these changes do not differ between physically active and inactive subjects.

Renal resistive index by transesophageal and transparietal echo-doppler imaging for the prediction of acute kidney injury in patients undergoing major heart surgery.

Acute kidney injury (AKI) following major heart surgery (MHS) is associated with early decrease in renal blood flow and worsened prognosis. Doppler-derived renal resistive index (RRI), which reflects renal vascular resistance, may predict the development of AKI in patients undergoing MHS. We studied 60 consecutive patients (mean age 69.5years, range 30-88, 41 males) undergoing MHS. We measured RRI, both at the renal sinus and intraparenchymally, by transesophageal echo-Doppler ultrasound (TE-EDus) at anesthesia induction and at the end of surgery in all patients. Additionally, we measured RRI by external transparietal echo-Doppler ultrasound (TP-EDus) at the following time points: anesthesia induction, end of surgery, 4 and 24h from cardiopulmonary bypass (CPB) start. We also measured serum neutrophil gelatinase associated lipocalin (NGAL) at the same time points. AKI [serum creatinine (sCr) increase ≥0.3mg/dl vs. baseline within 72h] developed in 23/60 (38.3%) patients, with two requiring dialysis. Systemic hemodynamic parameters were similar in the patients who developed AKI (AKI+) and in those who did not (AKI-). Intraparenchymal RRI at end-surgery was significantly higher in AKI+ compared to AKI- patients, both at TE-EDus and TP-EDus (TE-EDus mean difference, p=0.004; TP-EDus mean difference, p=0.013; difference between TE-EDus and TP-EDus results, p=0.066), although the predictive performance was limited with both methods (area under the curve [AUC] of the receiver-operator characteristics: 0.71 and 0.70 for TE-EDus and TP-EDus, respectively). Serum NGAL values were higher in AKI+than in AKI- patients (anesthesia induction, p=0.037; end-surgery, p=0.007; 4h from CPB start, p=0.093; 24h from CPB start, p=0.024. However, combining RRI with serum NGAL at end-surgery did not provide a clear-cut advantage in predicting AKI. In patients undergoing MHS, increased echo-Doppler ultrasound-derived RRI at end-surgery is significantly associated with the risk of AKI, but has limited practical utility for identifying the patients who will develop AKI.

Effect of diesel exhaust particles on renal vascular responses in rats with chronic kidney disease.

Several recent studies have indicated the possible association between exposure to particulate air pollution and the increased rate of morbidity and mortality in patients with kidney diseases. The link of this observation to vascular damage has not been adequately addressed. Therefore, this study aims to investigate possible vascular damage that might be associated with exposure to diesel exhaust particles (DP) in adenine (AD)-induced chronic kidney disease (CKD) in rats, and the possible ameliorative effect of gum acacia (GA). CKD was induced by feeding AD (0.75%, w/w), and DP (0.5 mg/kg) was instilled intratracheally every second day and GA was given concomitantly in the drinking water at a dose of 15% w/v. All treatments were given concomitantly for 28 days. Changes in renal blood flow (RBF) and systolic and diastolic blood pressure were monitored in these animals after anesthesia, together with several other endpoints. Exposure to DP significantly reduced RBF and this was significantly potentiated in AD-treated rats. Phenylephrine-induced decreases in RBF and increases in systolic and diastolic blood pressure were severely potentiated in rats exposed to DP, and these actions were significantly augmented in AD-treated rats. GA did not significantly affect the vascular impairment induced by AD and DP given together. This study provides experimental evidence that exposure to particulate air pollution can exacerbate the vascular damage seen in patients with CKD. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 541-549, 2017.

Acute Kidney Injury

Acute kidney injury (AKI) is defined as a syndrome in which there is an abrupt (hours to days) absolute increase in serum creatinine (SCr) of 0.5 mg/dL or a 25% increase from baseline. Even a modest rise in SCr of 0.3 mg/dL during hospitalization is associated with increased mortality and morbidity. Because of difficulties using SCr as a determinant of AKI, a variety of serum (neutrophil gelatinase–associated lipocalin, interleukin-18) and urine (kidney injury molecule–1) biomarkers of AKI are currently undergoing intense investigation. AKI may be defined pathophysiologically, as a decrease in renal blood flow (prerenal), or an intrinsic renal parenchymal disease (renal), or obstruction of urine flow (postrenal). Indications for emergent dialysis include hyperkalemia, fluid overload, acidosis, and signs and symptoms of uremia. If AKI is diagnosed in the emergency department, the patient should be admitted for further workup. In the majority of patients who survive AKI, renal function essentially returns to normal. Key words: acute kidney injury, dialysis, hyperkalemia, serum creatinine This review contains 3 highly rendered figures, 11 tables, and 49 references.

The potential protective effects of erythropoietin and estrogen on renal ischemia reperfusion injury in ovariectomized rats

BackgroundRenal ischemia–reperfusion (RIR) is an important etiopathological mechanism of acute renal failure (ARF). Erythropoietin (EPO) has been candidate as a nephroprotectant agent. However, its nephroprotective effect when it is accompanied with estrogen has not been studied in female. MethodsFifty-six female rats were divided into seven groups. Each formed of 8 rats. Group I: control group. Group II: Female rats exposed to RIR (named RIR group).Group III: Female rats exposed to RIR and pretreated with EPO (named RIR+EPO group). Group IV: ovariectomized rats exposed to RIR (named OVR+RIR group). Group V: ovariectomized rats received estrogen (E) then exposed to RIR (named OVR+RIR+E group). Group VI: ovariectomized rats received EPO before RIR (named OVR+RIR+EPO group). Group VII: ovariectomized rats received E then received EPO before RIR (named OVR+RIR+E+EPO group).Serum creatinine, blood urea nitrogen (BUN) and renal blood flow (RBF) were measured. Tumor necrosis factor-α (TNF-α), Myeloperoxidase activity (MPO), nitric oxide (NO), endothelin-1(ET-1) and EPO levels were assessed in the renal tissue. Histopathology was assessed to detect renal damage score. ResultsRIR significantly increased the serum levels of creatinine and BUN with decrease in RBF. In addition it significantly increased TNF-α, MPO and endothelin-1 levels with decrease in NO and EPO levels in renal tissue. However, these parameters significantly reversed by EPO except RBF. Combination of E and EPO leads to significant decrease in the protective effect of EPO. ConclusionIt seems that EPO could protect the kidney against RIR, while this protective effect was decreased when E was supplemented.

Variable responses of regional renal oxygenation and perfusion to vasoactive agents in awake sheep.

Vasoactive agents are used in critical care to optimize circulatory function, but their effects on renal tissue oxygenation in the absence of anesthesia remain largely unknown. Therefore, we assessed the effects of multiple vasoactive agents on regional kidney oxygenation in awake sheep. Sheep were surgically instrumented with pulmonary and renal artery flow probes, and combination fiber-optic probes, in the renal cortex and medulla, comprising a fluorescence optode to measure tissue Po2 and a laser-Doppler probe to assess tissue perfusion. Carotid arterial and renal venous cannulas enabled measurement of arterial pressure and total renal oxygen delivery and consumption. Norepinephrine (0.1 or 0.8 μg·kg(-1)·min(-1)) dose-dependently reduced cortical and medullary laser Doppler flux (LDF) and Po2 without significantly altering renal blood flow (RBF), or renal oxygen delivery or consumption. Angiotensin II (9.8 ± 2.1 μg/h) reduced RBF by 21%, renal oxygen delivery by 28%, oxygen consumption by 18%, and medullary Po2 by 38%, but did not significantly alter cortical Po2 or cortical or medullary LDF. Arginine vasopressin (3.3 ± 0.5 μg/h) caused similar decreases in RBF and renal oxygen delivery, but did not significantly alter renal oxygen consumption or cortical or medullary LDF or Po2. Captopril had no observable effects on cortical or medullary LDF or Po2, at a dose that increased renal oxygen delivery by 24%, but did not significantly alter renal oxygen consumption. We conclude that vasoactive agents have diverse effects on regional kidney oxygenation in awake sheep that are not predictable from their effects on LDF, RBF, or total renal oxygen delivery and consumption.

The renal nerves in chronic heart failure: efferent and afferent mechanisms.

The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF.

Glomerulosclerosis in the diet-induced obesity model correlates with sensitivity to nitric oxide inhibition but not glomerular hyperfiltration or hypertrophy

The diet-induced obesity (DIO) model is frequently used to examine the pathogenesis of obesity-related pathologies; however, only minimal glomerulosclerosis (GS) has been reported after 3 mo. We investigated if GS develops over longer periods of DIO and examined the potential role of hemodynamic mechanisms in its pathogenesis. Eight-week-old male obesity-prone (OP) and obesity-resistant (OR) rats (Charles River) were administered a moderately high-fat diet for 5 mo. Radiotelemetrically measured blood pressure, proteinuria, and GS were assessed. OP (n=10) rats developed modest hypertension (142±3 vs. 128±2 mmHg, P<0.05) and substantial levels of proteinuria (63±12 vs. 12±1 mg/day, P<0.05) and GS (7.7±1.4% vs. 0.4±0.2%) compared with OR rats (n=8). Potential hemodynamic mechanisms of renal injury were assessed in additional groups of OP and OR rats fed a moderately high-fat diet for 3 mo. Kidney weight (4.3±0.2 vs. 4.3±0.1 g), glomerular filtration rate (3.3±0.3 vs. 3.1±0.1 ml/min), and glomerular volume (1.9±0.1 vs. 2.0±0.1 μm3×10(-6)) were similar between OP (n=6) and OR (n=9) rats. Renal blood flow autoregulation was preserved in both OP (n=7) and OR (n=7) rats. In contrast, Nω-nitro-L-arginine methyl ester (L-NAME) administration in conscious, chronically instrumented OP (n=11) rats resulted in 15% and 39% increases in blood pressure and renal vascular resistance, respectively, and a 16% decrease in renal blood flow. Minimal effects of L-NAME were seen in OR (n=9) rats. In summary, DIO-associated GS is preceded by an increased hemodynamic sensitivity to L-NAME but not renal hypertrophy or hyperfiltration.

ET B Receptors in High Salt Diet‐Induced Decline of Renal Autoregulation in Rats

High salt (HS) diet is linked to increased endothelin-1 (ET-1) and salt-dependent hypertension. Previous studies showed that HS treatment increased renal microvascular ETB receptor expression and impaired renal blood flow (RBF) autoregulation. We hypothesized that HS leads to a decline of renal autoregulation via activation of ETB receptors. RBF autoregulation was assessed in anesthetized ETB deficient (ETB) and intact control littermates (Con) rats fed normal salt (NS) or HS (8% NaCl) for 2 weeks. RBF was monitored using an ultrasonic flow probe and autoregulation was assessed during step-decrements of arterial pressure imposed using an aortic occluder placed between the two renal arteries. ETB deficient rats (n=6) exhibited significantly elevated baseline mean arterial pressure (MAP, 132±5 vs. 116±1 mmHg in Con+NS, n=8, P<0.05). HS did not change MAP in either group but significantly increased RBF in Con rats (n=8, 12.5±0.7 vs. 9.2±0.5 ml/min.gkw in Con+NS, P<0.05) while decreasing RBF in ETB rats (6.8±0.6 ml/min.gkw vs. Con+NS, P<0.05). HS led to attenuated autoregulation of RBF in Con rats. Decreasing renal perfusion pressure from ambient to 95 mmHg resulted in an 11±2% decrease in RBF in Con+HS versus a 3±1% in Con+NS (P<0.05). Accordingly, autoregulatory index (AI) was 0.63±0.08 in Con+HS versus 0.18±0.09 in Con+NS (P<0.05). In contrast, RBF remained fairly stable in ETB+NS and ETB+HS rats during a stepwise reduction of renal perfusion pressure from ambient to 95 mmHg. AI averaged 0.26±0.14 and 0.12±0.24, respectively, suggesting intact autoregulation in ETB deficient rats. These data suggest that HS leads to attenuated RBF autoregulation and increased RBF via ETB receptoractivation.

Renal haemodynamic response to amino acids infusion in an experimental porcine model of septic shock.

Acute kidney injury (AKI) is common in sepsis. Treatments allowing maintenance of renal blood flow (RBF) could help to prevent AKI associated with renal hypoperfusion. Amino acids (AA) have been associated with an increase of RBF and glomerular filtration rate (GFR) in several species. The aim of this study was to evaluate the effects of an AA infusion on RBF and GFR in a porcine model of septic shock. A total of 17 piglets were randomly assigned into three groups: Sham (Sham, n = 5), sepsis without AA (S-NAA, n = 6), sepsis treated with AA (S-AA, n = 6). Piglets preparation included the placement of ultrasonic transit time flow probes around left renal artery for continuous RBF measurement; ureteral catheters for GFR and urine output evaluation; pulmonary artery catheter for cardiac output (CO) and pulmonary arterial pressure measurements. Mean arterial pressure (MAP) and renal vascular resistance (RVR) were also determined. Septic shock was induced with a live Pseudomonas aeruginosa infusion. Crystalloids, colloids and epinephrine infusion were used to maintain and restore MAP > 60 mmHg and CO > 80% from baseline. Renal haemodynamic did not change significantly in the Sham group, whereas RBF increased slightly in the S-NAA group. Conversely, a significant increase in RVR and a decrease in RBF and GFR were observed in the S-AA group. AA infusion was associated with a higher requirement of epinephrine [340.0 (141.2; 542.5) mg vs. 32.5 (3.8; 65.0) mg in the S-NAA group P = 0.044]. An infusion of amino acids impaired renal haemodynamics in this experimental model of septic shock.

Contrast-enhanced ultrasound evaluation of renal microcirculation in sheep.

BackgroundContrast-enhanced ultrasonography (CEUS) is a novel imaging modality to estimate microvascular perfusion. We aimed to assess renal cortical microcirculatory changes by CEUS during pharmacologically or mechanically induced modifications of renal blood flow (RBF) in experimental animals.MethodsWe implanted invasive transit-time Doppler flow probes and a vascular occluder around the renal artery in six Merino sheep. After induction of general anaesthesia, renal CEUS studies with destruction-replenishment sequences were performed at baseline and after different interventions aimed at modifying RBF. First, we administered angiotensin II (AngII) to achieve a 25% (AngII 25%) and 50% (AngII 50%) decrease in RBF. Then, we applied mechanical occlusion of the renal artery until RBF decreased by 25% (Occl 25%) and 50% (Occl 50%) of the baseline. Finally, a single dose of 25 mg of captopril was administered. CEUS sequences were analysed offline with dedicated software and perfusion indices (PI) calculated.ResultsPharmacological reduction of RBF with AngII was associated with a 62% (range: 68 decrease to 167 increase) increase (AngII 25%) and a 5% increase in PI (range: 92% decrease to 53% increase) (AngII 50%) in PI. Mechanical occlusion of the renal artery was associated with a 2% (range: 43% decrease to 2% increase) decrease (Occl 25%) and a 67% (range: 63% decrease to a 120% increase) increase (Occl 50%) in PI. The administration of captopril was associated with a 8% (range: 25% decrease to a 101% increase) decrease in PI. Pooled changes in PI failed to reach statistical significance. The study was limited by the difficulty to obtain high quality images.ConclusionsCEUS-derived parameters were highly heterogeneous in this sheep model. The current protocol and model did not allow the evaluation of the correlation between macro and microcirculation assessment by CEUS.

Ultrasonographic evaluation of abdominal organs after cardiac surgery

BackgroundDisturbances of the hepatosplanchnic region may occur after cardiac operations. Experimental studies have implicated impairment of splanchnic blood supply in major abdominal organ dysfunction after cardiopulmonary bypass (CPB). We investigated the impact of the cardiac operation and CPB on liver, kidney, and renal perfusion and function by means of ultrasonography and biochemical indices in a selected group of cardiac surgery patients. Materials and methodsSeventy five patients scheduled for a major cardiac operation were prospectively included in the study. Criteria for selection were moderate or good left ventricular ejection fraction and absence of previous hepatic or renal impairment. Ultrasound examination of the hepatic and renal vasculature and examination of biochemical parameters were performed on the day preceding the operation (T0), on the first postoperative day (T1), and on the seventh postoperative day (T2). ResultsPortal vein velocity and flow volume increased significantly, whereas hepatic artery velocity and flow volume decreased at T1 in comparison with T0. Hepatic vein indices remained unaffected throughout the observation period. Renal artery velocity and flow decreased, whereas renal pulsatility index and renal resistive index increased at T1 as compared with T0. Aspartate aminotransferase and alanine aminotransferase values were increased as compared with baseline values 24 h postoperatively. All parameters displayed a trend to approach preoperative levels at T2. Strong negative correlations between alanine aminotransferase values at T1 and hepatic artery velocity and flow volume at the same time point were also demonstrated (R = 0.638, P < 0.001 and r = 0.662, P < 0.001, respectively). ConclusionsThe increase in portal vein flow and velocity and the decrease in hepatic artery flow and velocity in the period after CPB might be attributed to the hypothermic bypass technique and the hepatic arterial buffer response, respectively. The decrease in renal blood flow and velocity and the parallel increase in Doppler renal pulsatility index and renal resistive index could be considered as markers of kidney hypoperfusion and intrarenal vasoconstriction. Maintaining a high index of suspicion for the early diagnosis of noncardiac complications in the period after CPB and institution of supportive care in case of compromised splanchnic perfusion are warranted.

General anesthesia type does not influence serum levels of neutrophil gelatinase-associated lipocalin during the perioperative period in video laparoscopic bariatric surgery

OBJECTIVES:Video laparoscopic bariatric surgery is the preferred surgical technique for treating morbid obesity. However, pneumoperitoneum can pose risks to the kidneys by causing a decrease in renal blood flow. Furthermore, as in other surgical procedures, laparoscopic bariatric surgery triggers an acute inflammatory response. Neutrophil gelatinase-associated lipocalin is an early and accurate biomarker of renal injury, as well as of the inflammatory response. Anesthetic drugs could offer some protection for the kidneys and could attenuate the acute inflammatory response from surgical trauma. The objective of this study was to compare the effects of two types of anesthetics, propofol and sevoflurane, on the serum levels of neutrophil gelatinase-associated lipocalin during the perioperative period in laparoscopic bariatric surgery.METHODS:Sixty-four patients scheduled for laparoscopic bariatric surgery were randomized into two anesthesia groups and were administered either total intravenous anesthesia (propofol) or inhalation anesthesia (sevoflurane). In the perioperative period, blood samples were collected at three time points (before anesthesia, 6 hours after pneumoperitoneum and 24 hours after pneumoperitoneum) and urine output was measured for 24 hours. Acute kidney injuries were evaluated by examining both the clinical and laboratory parameters during the postoperative period. The differences between the groups were compared using non-parametric tests. ReBEC (http://www.ensaiosclinicos.gov.br/rg/recruiting/): RBR-8wt2fyRESULTS:None of the patients developed an acute kidney injury during the study and no significant differences were found between the serum neutrophil gelatinase-associated lipocalin levels of the groups during the perioperative period.CONCLUSION:The choice of anesthetic drug, either propofol or sevoflurane, did not affect the serum levels of neutrophil gelatinase-associated lipocalin during the perioperative period in laparoscopic bariatric surgery.

Curcumin prevents maleate-induced nephrotoxicity: Relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I

The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl β-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production.

Abstract 631: Maternal Separation (msep) Alters Baroreflex Function And Renal Blood Flow Responsiveness

An impairment of the baroreflex buffering has been shown to precede the development of hypertension. Formerly, we reported that MSep, a model of behavioral stress during early life, impairs chronic blood pressure control and renal filtration capacity. Thus, the aim of this study was to study the baroreflex function and renal blood flow regulation in MSep rats. We used 3 month-old MSep male rats, anesthetized with isoflurane. Femoral vein catheter was fitted to infuse saline (3 ml/hr, baseline), PE (phenylephrine, 1 ug/ml, 9 ml/hr) or SNP (sodium nitroprusside, 0.5 ug/ml, 9 ml/hr). Femoral artery catheter was fitted to collect blood pressure and HR data (ADInstruments). In addition, a flow probe was placed in the left renal artery for renal blood flow (RBF) assessment (Transonic). After 45 minutes of baseline, PE infusion (2 min) was performed. Following 30-minute recovery period, SNP infusion (2 min) was achieved. Delta heart rate (HR)/Delta mean arterial pressure (MAP) relationship shows a significant difference in the slopes between MSep vs. control rats (-0.5 ±0.07 vs. -1.08 ±0.08, p&lt;0.05). PE-induced decrease in RBF was attenuated in a dose dependent manner in MSep rats (max. delta RBF -4.8±0.8 ml/min) compared to controls (max. delta RBF -7±1.5 ml/min, p&lt;0.05, respectively). Yet, renal vascular resistance (MAP/RBF) was not different between MSep and control rats along the 2-min period (slope: 0.43±0.02 vs. 0.42±0.03 mmHg/ml/min, respectively). These data suggest that MSep rats fail to increase HR in response to a vasodilatory agent and lower HR in response to vasoactive stimulus. Furthermore, attenuated alpha-adrenergic-induced renal vascular responses support the existence of a compensatory mechanism in response to an increased sympathetic outflow to the kidney, as previously suggested. The contribution of the different components of the autonomic nervous system is the focus of ongoing studies.