Bilateral Renal Artery Research Articles

#5449 CALYCOSIN ATTENUATES RENAL ISCHEMIA/REPERFUSION INJURY BY SUPPRESSING INFLAMMATION VIA PPARγ/EGR1 PATHWAY

Abstract Background and Aims Renal ischemia reperfusion injury (IRI) is a leading and common cause of AKI, and delayed recovery of IRI contributes to chronic kidney disease and even end-stage kidney disease. However, there is no effective prevention and treatment for IRI-AKI. Calycosin (CAL), an isoflavonoid phytoestrogen isolated from Radix astragali, has various pharmacological activities. However, whether CAL has a protective effect on renal IRI and its mechanism remains elusive. In this study, we aim to explore the effect and mechanism of CAL on IRI-AKI through bioinformatics and experiments in vitro and in vivo models, so as to provide potential candidate drugs for early intervention treatment of IRI-AKI. Method (1) In the first part, mice were intragastrically given CAL daily for 7 d, and subjected to bilateral renal artery occlusion for 35 min followed by reperfusion 24 h to establish the renal IRI model. HE staining was used to evaluate the renal pathological injury, and the renal function including serum creatinine (SCr) and blood urea nitrogen (BUN), was also examined. Meanwhile, inflammatory factors were detected. In cell experiments, HK-2 cells pretreated with 8,16 and 32 μM CAL were subjected with hypoxia/reoxygenation (H/R), and the effect of CAL on H/R induced cell injury were investigated by qRT-PCR and ELISA. (2) In the second part, the differentially expressed gene (DEGs) of IRI-AKI were obtained by bioinformatics analysis of GSE52004 dataset. Subsequently, the hub gene with the highest score was obtained by protein-protein interaction (PPI) analysis, and its upstream transcription factors were predicted by JASPAR database. In IRI-AKI mice, the predicted results of bioinformatics were verified by qRT-PCR, Western Blot and immunohistochemistry. In HK-2 cells, the regulatory relationship between the hub gene and its upstream transcription factor and the role of them in inflammatory process were verified by double luciferase reporter gene and siRNA. Furthermore, molecular docking was used to predict the interaction between CAL and the transcription factor, and the role of the target protein in the protection of H/R HK-2 cells by calycosin was verified by siRNA. Results (1) In the mice with renal IRI, CAL dose dependently alleviated SCr and BUN levels and renal tubular injury score. Meanwhile, the mRNA levels and concentrations of inflammatory cytokines were markedly inhibited by CAL pretreatment. (2) In the pre-experiment in vitro, the toxicity of CAL was negligible at concentrations of 32 μM or less for 24 h incubation. In H/R induced HK-2 cells, CAL incubation reduced the levels of hypoxia-inducible factor 1α (HIF-1α) and the inflammatory cytokines. (3) 58 DEGs were identified in the kidney of IRI mice. PPI analysis showed early growth response 1 (EGR1) is the hub gene the highest score. JASPAR database predicted that peroxisome proliferator-activated receptor γ (PPARγ) is the upstream transcription factor of EGR1. (4) In kidney after IRI, EGR1 was up-regulated and PPARγ was down-regulated, while the pretreatment of CAL decreased EGR1 and increased PPARγ in a dose-dependent manner. (5) In H/R induced HK-2 cells, after inhibited the expression of EGR1 by siRNA, the level of inflammatory factors decreased significantly, suggesting that EGR1 participated in and promoted the inflammatory process of tubular cells. In addition, dual luciferase reporter gene assay confirmed that PPARγ interact with EGR1 promoter, as EGR1 increased after EGR1 promoter plasmid transfection but decreased after PPARγ overexpression. (6) In mice after renal IRI, CAL promote PPARγ expression markedly. According to molecular docking, CAL, as a ligand, could be embedded into the orthosteric pocket of PPARγ with a binding energy of -6.46 kcal/mol. In CAL incubated cells, PPARγ increased and EGR1 decreased considerably. However, the protective effect of CAL on H/R induced inflammation was absent when PPARγ knockdown, indicated that CAL ameliorate renal IRI and inhibit inflammation via PPARγ/EGR1. Conclusion CAL could significantly modulate inflammation by targeting the PPARγ/EGR1 pathway, contributing to the alleviation of renal IRI.

Bilateral renal artery stenosis impacts postoperative complications after major vascular surgery

BackgroundIncidental atherosclerotic renal artery stenosis (RAS) is common in patients undergoing vascular surgery and has been shown to be associated with postoperative AKI among patients undergoing major non-vascular surgeries. We hypothesized that patients with RAS undergoing major vascular procedures would have a higher incidence of AKI and postoperative complications than those without RAS. MethodsA single-center retrospective cohort study of 200 patients who underwent elective open aortic or visceral bypass surgery (100 with postoperative AKI; 100 without AKI) were identified. RAS was then evaluated by review of pre-surgery CTAs with readers blinded to AKI status. RAS was defined as ≥50 % stenosis. Univariate and multivariable logistic regression was used to assess association of unilateral and bilateral RAS with postoperative outcomes. Results17.4 % (n = 28) of patients had unilateral RAS while 6.2 % (n = 10) of patients had bilateral RAS. Patients with bilateral RAS had similar preadmission creatinine and GFR as compared to unilateral RAS or no RAS. 100 % (n = 10) of patients with bilateral RAS had postoperative AKI compared with 45 % (n = 68) of patients with unilateral or no RAS (p < 0.05). In adjusted logistic regression models, bilateral RAS predicted severe AKI (OR 5.82; CI 1.33, 25.53; p = 0.02), in-hospital mortality (OR 5.71; CI 1.03, 31.53; p = 0.05), 30-day mortality (OR 10.56; CI 2.03, 54.05; p = 0.005) and 90-day mortality (OR 6.88; CI 1.40, 33.87; p = 0.02). ConclusionsBilateral RAS is associated with increased incidence of AKI as well as in-hospital, 30-day, and 90-day mortality suggesting it is a marker of poor outcomes and should be considered in preoperative risk stratification.

Knockdown of histone deacetylase 1 in fibroblasts and pericytes prevents renal interstitial fibrosis after ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI), one form of acute kidney failure, often occurs after cardiovascular or renal surgery where there is a decline in blood flow through the kidney. This injury causes damage to renal cells and can lead to the formation of interstitial fibrosis, which will increase the risk of chronic kidney disease. The histone deacetylases (HDAC) protein family controls the expression of genes via epigenetic regulation of deacetylating histone lysine residues. We published that within an hour of bilateral IRI, in male mice, there was an increase of HDAC1 in the epithelium and interstitial cells. Moreover, inhibition of HDAC1 prior to IRI resulted in attenuated interstitial fibrosis. Myofibroblasts secrete collagen contributing significantly to wound healing as well as the development of interstitial fibrosis and these cells are predominantly differentiated fibroblasts and pericytes. We hypothesized that the knockdown of HDAC1 in fibroblasts and pericytes will attenuate interstitial fibrosis in the kidney after IRI. Male control (HDAC1fl/fl) and iFibroblastHDAC1KO (HDAC1fl/fl, Col1A2-CreER, hemizygous mice) were used in the experiment. The mice underwent bilateral renal artery and vein clamping for 18 minutes to induce IRI or sham surgery. Acute kidney injury was confirmed by serum creatinine measurements and determination of glomerular filtration rate (GFR) by transcutaneous FITC-sinistrin clearance 24 hours after injury. GFR was measured weekly for 4 weeks at which point the blood and kidneys were collected for analysis. Renal interstitial fibrosis was quantified by measuring the percentage coverage area of collagen stained by picrosirius red staining. 24 hours after surgery, IRI mice serum creatinine levels were greater in control mice 0.53 mg/dl ± 0.17, n = 9, and iFibHDAC1KO IRI mice 0.25 mg/dl ± 0.053, n = 10, compared to sham mice (control 0.084 mg/dl ± 0.008, n = 5, KO 0.098 mg/dl ± 0.006, n = 4, Pgenotype = 0.3, Psurgery = 0.028, Pinteraction = 0.25). This agreed with the measured GFR that was significantly reduced in the IRI mice (control IRI = 426 ul/min/100g ± 132, KO IRI = 529 ul/min/100g ± 116, Sham control = 1180 ul/min/100g ± 178, sham KO = 1188 ul/min/100g ± 156, Pgenotype = 0.71, Psurgery = 0.0003, Pinteraction = 0.75). The percentage of the collagen-positive area was significantly higher in control than in sham mice (p = 0.0011), while there was no noticeable difference (p = 0.9) between iFibHDAC1KO and sham mice (control IRI = 1.2 % ± 0.2, KO IRI = 0.47% ± 0.12, sham control = 0.35% ± 0.085, sham KO = 0.401% ± 0.073). In conclusion, HDAC1 is activated by IRI in the myofibroblast and promotes interstitial fibrosis. Funding resources: NIH NIDDK R01DK126664, UAB-UCSD O'Brien Center, and the Priya Nagar M.D. Foundation. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

CORONARY ARTERY BYPASS SURGERY IN YOUNG ADULT A INSTITUTIONAL RETROSPECTIVE STUDY

Objective: To study the overall causes, perioperative mortality, post operative complications, prognosis, outcome and follow up in a young adult present with coronary artery disease under going coronary artery bypass in our institute. Methods: Asum of 56 patient who are 40 years and less then 40 years who underwent coronary artery bypass surgery between January 2017 to December 2022 who's clinical case history, coronary angiography, pre operative and post operative echo cardiography, operative notes, post operative notes, outpatient follow up are collected from our computer stored data and from medical record department in our college and from Tamilnadu chief minister comprehensive health insurance scheme institutional Web site data base Results: Out of 56 patient,8 Female(14.3%) and 48 Male(85.7%),mean age 37.1 years (range 32 – 40 years),Diabetic 39 Patient (62.5%),Hypertensive 21 patient (37.5%) 7 / 8 women(87.5%) diabetic ,3/8 women both diabetic and hypertensive. Out of 48 male 47(97.9%) chronic smoker, 45 (93.8%) chronic alcoholic,44 (91.6%) both alcoholic and smoke , no women in this study neither alcoholic or smoker, 3patient (5.35%) hyperlipidaemia, 2 patient (3.57%) hypothyroidism all 2/8 (25%) are female,2 patient on haemodialysis for kidney disease, 1patient with bilateral renal artery stenosis, 1 patient with right innominate, right subclavian, bilateral carotid stenosis. Left ventricular function was impaired with ejection fraction average 46% (range 30% - 55%). 1 patient with ventricular septal rupture.2 patient with post coronary stent, The indication for surgery was triple vessel disease in 30 patient(53.57%) ,double vessel disease in 20 patient(35.7%),single vessel disease in 1 patient, single vessel disease with ventricular septal rupture in 1 patient, left main coronary artery stenosis in 4 patient(7%). Surgical procedure Off pump coronary artery bypass surgery in 51 patient(91%), On pump beating heart coronary artery bypass surgery in 2 patient (3.57%),On pump arrested heart coronary artery bypass surgery in 3 patient(5.35%). A total of 132 grafts were constructed(mean 2.4 grafts per patient),35 (27%) of them being arterial only left internal mammary artery harvested and other grafts were great saphenous vein. Post operative average ventilation time18hrs (range 18hrs to 24hrs), There were 5(8.9%)hospital death and 5(8.9%) late death in follow up, total 10 (17.8%) death till now. Conclusion: Most common cause for young coronary artery disease from our clinical history is found to be early onset diabetic mellitus and from our personal history chronic smoking and chronic alcoholism, intra operative mortality and morbidity is high in patient present with severe left ventricular dysfunction, coronary artery diseases induced complication and additional comorbidity, however most of patient recovered from post operative cardiovascular lethal or morbid event and on regular clinical follow up

Mitochondria and renal microvascular dysfunction following ischemia-reperfusion in rats

The pathophysiological mechanisms underlying ischemia-reperfusion (IR) induced acute kidney injury (AKI) remain poorly understood. Preglomerular microvessels (PGMV), specifically afferent arterioles, possess an intrinsic autoregulatory ability that is vital for ensuring stable renal hemodynamics. Our recent study indicates that renal autoregulation is impaired in IR rats due to reactive oxygen species (ROS) accumulation. We hypothesized that mitochondria-derived ROS (mtROS) in preglomerular microvessels contribute to renal autoregulatory impairment in IR rats. Blood-perfused juxtamedullary nephron experiments were performed on kidneys of male Sprague-Dawley rats 24 hours after IR induction (60-min, bilateral renal artery clamping). Afferent arteriolar autoregulation was assessed as perfusion pressure (PP) was increased from 65 to 170 mmHg in 15 mmHg increments. Afferent arterioles of sham-operated control rats (n=7) established pressure-mediated autoregulatory responses. Baseline diameter (100 mmHg) averaged 13.2±0.4 μm and increased to 114±4% of baseline when PP decreased from 100 to 65 mmHg. Diameter decreased to 65±3% of baseline when PP increased to 170 mmHg. In contrast, afferent arterioles from IR rats lost autoregulatory capability and remained between 90 and 100% of baseline diameter over 65-170 mmHg (n=8). Addition of Mito-Tempo (mitochondria-targeted antioxidant, 0.1 mM, n=3) to the perfusate restored autoregulation in IR rats at lower PP (65-125 mmHg, P&gt;0.05 vs sham) and partially restored it over 140-170 mmHg. Superfusion with oligomycin (ATP synthase inhibitor, 2.5 μM) in normal kidneys evoked vasodilation to 178±13% baseline and blunting of autoregulatory reactivity. Renal autoregulation is linked to ATP-sensitive P2X1-receptor signaling. Changes in ATP-induced intracellular calcium concentration ([Ca2+]i) were assessed in isolated PGMV myocytes using Fura-2 fluorescent dye. IR markedly attenuated [Ca2+]i responses to 10 and 100 μM ATP by 46±11% and 57±15%, respectively (P&lt;0.05, n=3-4 rats/group), and blunted ATP-induced afferent arteriolar vasoconstriction ( P&lt;0.05 vs. sham, n=3/group). IR markedly increased the fluorescence intensity of mitoROS (MitoSOX™ kit) in PGMV compared to sham rats. Mitochondrial respiratory function was assessed using High Resolution Respirometry in freshly isolated PGMV (n=3/group). IR significantly reduced basal respiration (20±4 vs. 58±9 pmol/s·ml in sham, P&lt;0.05) and oxidative phosphorylation capacity (51±10 vs. 219±37 pmol/s·ml in sham, P&lt;0.05). The percentage of ATP-linked respiration was also reduced in PGMV of IR (60±2% vs. 75±2% in sham, P&lt;0.05). In conclusion, mitochondria of PGMV are involved in regulating renal microvascular tone and autoregulation. IR leads to autoregulatory dysfunction by causing mitochondrial dysfunction in PGMV, increased mtROS production and suppression of ATP-dependent calcium signaling. This study is supported by grants R01DK106500. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Emodin prevents renal ischemia-reperfusion injury via suppression of p53-mediated cell apoptosis based on network pharmacology

BackgroundPrevious evidence indicated that emodin has significant advantages for preventing acute kidney injury (AKI). However, the mechanisms responsible for these effects of emodin have yet to be elucidated. MethodsWe first used network pharmacology and molecular docking to identify the core targets of emodin for AKI and performed a range of experiments to validate this result. Pretreatment with emodin for 7 days, the rats were treated with bilateral renal artery clipping for 45 min to identify the prevention effect. Hypoxia/reoxygenation (H/R), and vancomycin - induced renal tubular epithelial cells (HK-2 cells) were treated with emodin to explore the related molecular mechanism. ResultsNetwork pharmacology and molecular docking showed that anti-apoptosis might be the core mechanism responsible for the action of emodin on AKI; this anti-apoptotic effect appears to because by regulation p53-related signaling pathway. Our data showed that pretreatment with emodin significantly improved renal function and renal tubular injury in renal I/R model rats (P < 0.05. The prevention effect of emodin was proved to be related to anti - apoptosis of HK-2 cells, possibly by downregulating the levels of p53, cleaved-caspase-3, pro-caspase-9, and upregulated the levels of Bcl-2. The efficacy and mechanism of emodin on anti - apoptosis was also confirmed in vancomycin - induced HK-2 cells. Meanwhile, the data also showed that emodin promoted angiogenesis in I/R damaged kidneys and H/R-induced HK-2 cells, which was associated with decreasing HIF-1α levels and increasing VEGF levels. ConclusionsOur findings indicated that the preventive effect of emodin on AKI is probably attributable to anti-apoptosis response and promoting angiogenesis effect.

Renal Denervation Helps Preserve the Ejection Fraction by Preserving Endocardial-Endothelial Function during Heart Failure.

Renal denervation (RDN) protects against hypertension, hypertrophy, and heart failure (HF); however, it is not clear whether RDN preserves ejection fraction (EF) during heart failure (HFpEF). To test this hypothesis, we simulated a chronic congestive cardiopulmonary heart failure (CHF) phenotype by creating an aorta-vena cava fistula (AVF) in the C57BL/6J wild type (WT) mice. Briefly, there are four ways to create an experimental CHF: (1) myocardial infarction (MI), which is basically ligating the coronary artery by instrumenting and injuring the heart; (2) trans-aortic constriction (TAC) method, which mimics the systematic hypertension, but again constricts the aorta on top of the heart and, in fact, exposes the heart; (3) acquired CHF condition, promoted by dietary factors, diabetes, salt, diet, etc., but is multifactorial in nature; and finally, (4) the AVF, which remains the only one wherein AVF is created ~1 cm below the kidneys in which the aorta and vena cava share the common middle-wall. By creating the AVF fistula, the red blood contents enter the vena cava without an injury to the cardiac tissue. This model mimics or simulates the CHF phenotype, for example, during aging wherein with advancing age, the preload volume keeps increasing beyond the level that the aging heart can pump out due to the weakened cardiac myocytes. Furthermore, this procedure also involves the right ventricle to lung to left ventricle flow, thus creating an ideal condition for congestion. The heart in AVF transitions from preserved to reduced EF (i.e., HFpEF to HFrEF). In fact, there are more models of volume overload, such as the pacing-induced and mitral valve regurgitation, but these are also injurious models in nature. Our laboratory is one of the first laboratories to create and study the AVF phenotype in the animals. The RDN was created by treating the cleaned bilateral renal artery. After 6 weeks, blood, heart, and renal samples were analyzed for exosome, cardiac regeneration markers, and the renal cortex proteinases. Cardiac function was analyzed by echocardiogram (ECHO) procedure. The fibrosis was analyzed with a trichrome staining method. The results suggested that there was a robust increase in the exosomes' level in AVF blood, suggesting a compensatory systemic response during AVF-CHF. During AVF, there was no change in the cardiac eNOS, Wnt1, or β-catenin; however, during RDN, there were robust increases in the levels of eNOS, Wnt1, and β-catenin compared to the sham group. As expected in HFpEF, there was perivascular fibrosis, hypertrophy, and pEF. Interestingly, increased levels of eNOS suggested that despite fibrosis, the NO generation was higher and that it most likely contributed to pEF during HF. The RDN intervention revealed an increase in renal cortical caspase 8 and a decrease in caspase 9. Since caspase 8 is protective and caspase 9 is apoptotic, we suggest that RDN protects against the renal stress and apoptosis. It should be noted that others have demonstrated a role of vascular endothelium in preserving the ejection by cell therapy intervention. In the light of foregoing evidence, our findings also suggest that RDN is cardioprotective during HFpEF via preservation of the eNOS and accompanied endocardial-endothelial function.

Renovascular Hypertension with Progressive Atherosclerotic Renal Artery Stenosis in an Elderly Patient with Known Fibromuscular Dysplasia: A Case Report.

BACKGROUND Atherosclerotic renal artery stenosis (ARAS) and renovascular fibromuscular dysplasia (FMD) are 2 of the most common etiologies of renovascular hypertension. They have different pathophysiologies, risk factors, presentations, and treatment options. However, as our population ages, it can become increasingly common to see patients who previously had FMD who develop ARAS at an advanced age, indicated by recurrent renovascular hypertension. CASE REPORT We present a case of a 66-year-old female patient who, in 2007, had presented with uncontrolled hypertension. She underwent magnetic resonance angiography and was found to have bilateral FMD, for which she received balloon angioplasty to a severe lesion on the mid-right renal artery and subsequently had normalization of blood pressures and resolution of symptoms. In 2021 she returned with uncontrolled hypertension while being treated with 3 antihypertensives. Bilateral renal arteriography revealed new severe ostial stenosis of the left renal artery and a patent right renal artery in which balloon angioplasty was performed 14 years ago. Based on the angiographic pattern of this new left RAS, we concluded this lesion was caused by atherosclerosis. The left ostial lesion was treated with a bare-metal stent and the patient was continued on antihypertensive medication and statin; at follow-up 4 months later, her blood pressures had normalized. CONCLUSIONS This case features a patient who developed severe ARAS with underlying history of bilateral renal artery FMD. Clinicians need to be aware that in patients with FMD, worsening renovascular hypertension at an advanced age could indicate the development of new hemodynamically significant ARAS. These patients need repeat diagnostic testing and treatment with medial optimization with or without endovascular revascularization in the appropriate clinical setting.

Clinical study on the classification of renal artery involvement and comparison of renal function and prognosis of Stanford type B aortic dissection after thoracic aortic endovascular repair

Objective: To investigate the different types of renal artery involvement in Stanford type B aortic dissection (TBAD) and the comparison of clinical effecacy after thoracic endovascular aortic repair (TEVAR). Methods: This is a retrospective cohort study included 330 patients with TBAD and renal artery involvement treated with TEVAR from June 2002 to September 2021 in General Hospital of Northern Theater Command of the PLA. According to aortic CTA image, unilateral renal artery involvement conditions were divided into 5 types: the true lumen type (renal artery opening completely from the true lumen), false lumen type (renal artery opening completely from the false lumen), double lumen type (renal artery opening from the true and false double lumen), compression type (renal artery opening connected with the true lumen, but the renal artery opening was extremely squeezed by the inner membrane), open type (renal artery opening with intimal tear). There were seven types of bilateral renal artery involvement: true-true type (true lumen-true lumen type), true and false type (true lumen-false lumen type), true-double type (true lumen-double lumen type), true-opening type (true lumen-opening type), false-false type (false lumen-false lumen type), false-compression type (false lumen-compression type), double-double type (double lumen-double lumen type). The primary observation index of this study was the comparison of postoperative renal function and the incidence of clinical adverse events of different types of renal artery involvement. One-way ANOVA test, Kruskal-Wallis H test and paired sample rank sum test were used to compare postoperative renal function between different types of bilateral renal artery involvement. The Chi-square test or Fisher's exact probability test were used to compare the near and long term adverse events between different types of bilateral renal artery involvement. Kaplan-Meier method was used to compare the all-cause mortality of patients with severe renal functional injury and non-severe renal functional injury before surgery. Results: The average age of the patients included in this study was (53±11) years, including 276 males (83.6%) and 54 females (16.4%). There were statistical difference in the level of serum creatinine (preoperative:H=18.686, P=0.005, postoperative:H=18.101, P=0.006) and cystatin C (preoperative:H=17.566, P=0.007, postoperative:H=10.433, P=0.016), pre-and post-operative, between the seven groups of TBAD patients with different renal artery involvement types (P<0.05), and the false-false type group shown the worst kidney function. However, no statistically significant differences were shown when comparing their pre- and post-operative change values (P>0.05). The 30-day follow-up result showed that there were statistically significant differences in the incidence of postoperative acute kidney injury (χ2=15.623, P=0.007), aorta-related adverse events (χ2=15.523, P=0.010), and intraoperative endoleak (χ2=17.935, P=0.004) among the seven groups, and the false-false group was the highest (2/9, 5/9 and 5/9, respectively). In terms of long-term follow-up results, there were statistically significant differences in all-cause death (χ2=14.772, P=0.011) and non-aortic death (χ2=15.589,P=0.008) among the seven groups. Kaplan-Meier survival analysis showed that patients with worse pre-operative renal function showed higher long-term all cause death (17.7% vs. 4.8%, P=0.009). Conclusions: For TBAD patients with renal artery involvement, there were differences in renal function among different types, and TEVAR showed no significant effect on renal function in TBAD patients. The long-term all cause death was higher in patients with worse renal function pre-operative.

Renal denervation alleviates chronic obstructive sleep apnea-induced atrial fibrillation via inhibition of atrial fibrosis and sympathetic hyperactivity.

Previous studies have reported that renal denervation (RDN) prevents the occurrence of atrial fibrillation (AF) related to obstructive sleep apnea (OSA). However, the effect of RDN on chronic OSA (COSA)-induced AF is still unclear. Healthy beagle dogs were randomized into the OSA group (sham RDN + OSA), OSA-RDN group (RDN + OSA), and CON group (sham RDN + sham OSA). The COSA model was built via repeated apnea and ventilation rounds for 4h each day lasting 12weeks, and RDN was employed after 8weeks of modeling. All dogs were implanted Reveal LINQ™ to detect spontaneous AF and AF burden. Circulating levels of norepinephrine, angiotensin II, and interleukin-6 were determined at baseline and end of the study. In addition, measurements of the left stellate ganglion, AF inducibility, and effective refractory period were conducted. The bilateral renal artery and cortex, left stellate ganglion, and left atrial tissues were collected for molecular analysis. Of 18 beagles, 6 were randomized to each ofthe groups described above.RDN remarkably attenuated ERP prolongation and AF episodes and duration. RDN markedly suppressed the LSG hyperactivity and atrial sympathetic innervation, decreased the serum concentrations of Ang II and IL-6, further inhibited fibroblast-to-myofibroblast transformation via the TGF-β1/Smad2/3/α-SMA pathway, and reduced the expression of MMP-9, thus decreasing OSA-induced AF. RDN may reduce AF by inhibiting sympathetic hyperactivity and AF in a COSA model.

Hindsight is 20/20, an unexpected ocular telltale sign of bilateral renal artery dissection

Hindsight is 20/20, an unexpected ocular telltale sign of bilateral renal artery dissection

Paeoniflorin alleviates ischemia/reperfusion induced acute kidney injury by inhibiting Slc7a11-mediated ferroptosis

The pathophysiological mechanism of acute kidney injury (AKI) is complicated, and effective drugs are still lacking. Ferroptosis is a newly discovered regulatory cell death mode characterized by the lethal accumulation of iron and reactive oxygen species-(ROS-)-dependent lipid hydroperoxides. In recent years, ferroptosis has been confirmed to be involved in the progression of AKI. Paeoniflorin (PF) is a traditional Chinese medicine that has protective effects on a variety of kidney diseases including AKI. However, the mechanism by which PF attenuates AKI is unclear. We detected that PF attenuated serum biochemical markers, histological damage, ferroptosis and inflammation in a dose-dependent manner in a mouse AKI model with bilateral renal artery ischemia–reperfusion (IR). Hypoxia-reoxygenation (HR)-induced ferroptosis and inflammation was also inhibited by PF in human renal tubular epithelial cells (HK2). RNA sequence analysis revealed that PF inhibited ferroptosis in HK2 cells by upregulating Slc7a11 in the glutathione pathway after HR treatment. PF failed to further protect cells with specific knockdown of Slc7a11 from ferroptosis under HR conditions. Consequently, these data indicated that PF prevention of ferroptosis in AKI requires dependence on Slc7a11. This study provided a scientific basis for the clinical search for drugs to prevent IR induced AKI.

Myrrh Essential Oil Mitigates Renal Ischemia/Reperfusion-Induced Injury.

Ischemia/reperfusion (I/R)-induced renal injury is a common reason for kidney injury in clinical settings; therefore, continuous investigation of novel nephroprotective agents is crucial. Myrrh, the oleoresin exudates generated by the genus Commiphora, display numerous pharmacological actions. This study tried to assess the preventive effects of myrrh essential oil against I/R-induced renal damage. Rats were randomized into five groups. In the sham group, the animals were subjected to bilateral renal artery separation with no occlusion. In the sham + myrrh group; the rats were administered myrrh essential oil and then treated similarly to the sham group. Renal I/R group: the animals were challenged with renal I/R. In the myrrh + renal I/R groups, rats were administered 50 or 100 mg/kg of myrrh essential oil orally for three weeks before being confronted with I/R. Serum levels of renal function tests and renal injury biomarkers, including NGAL, KIM-1, and CysC, were amplified in the renal I/R group. Animals that experienced renal I/R exhibited elevated lipid peroxidation (MDA); declined SOD, CAT, and GPx activity; declined GSH content; augmented TLR4/NFκB gene expression; and subsequent enhancement of inflammatory mediators (TNF-α, IFN-γ, IL-1β, and IL-6). Myrrh reduced renal function tests and injury biomarkers and amended renal histological alterations. Pretreatment with myrrh reduced MDA, elevated the antioxidant enzymes' activities and GSH content, and reduced the TLR4 and NFκB gene expression, leading to subsequent inflammation and apoptosis alleviation. The outcomes of the present investigation established the protective effect of myrrh essential oil against renal I/R via pointing out the antioxidant, anti-inflammatory, and anti-apoptotic effects of myrrh.

Early Branching of Bilateral Renal Arteries with Bilateral Accessory Renal Arteries: A Case Report of a Live-Related Donor Transplantation

Comprehensive preoperative evaluation of potential donors is crucial for selecting the right donor, with adequately functioning kidneys, and the best surgical approach for harvesting the organs to prevent donor-related complications and to assure good recipient graft function. Multidetector computed tomography is the choice of imaging in the preoperative evaluation of living renal donors with an accuracy of 95%–100%. The donor must retain one normal kidney. The left kidney is preferred for living donor nephrectomy because it has a longer renal vein and it is technically easier to remove. It is always preferable to choose kidneys with a single artery because both donor and recipient surgeries are less complicated and there is less risk for arterial thrombosis. We report in a case of successful transplantation wherein the donor had an early division of the main renal artery bilaterally as well as bilateral accessory renal arteries.

Prion Protein Overexpression in Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Effectively Protected Rodent Kidney Against Ischemia-Reperfusion Injury Via Enhancing ATP/Mitochondrial Biogenesis—Role of ADMSC Rejuvenation and Proliferation

Background: We tested the hypothesis that overexpression of cellular-prion-protein in adipose-derived mesenchymal stem cells (PrPCOE-ADMSCs) effectively protected the kidney against ischemia-reperfusion (IR) injury in rat. Methods: Part I of cell culture was categorized into A1(ADMSCs)/A2(ADMSCs+p-Cresol)/A3(PrPCOE in ADMSCs)/A4 (PrPCOE in ADMSCs+p-Cresol). Part II of cell culture was divided into B1(ADMSCs)/B2[ADMSCs+lipopolysaccharide (LPS)]/B3(PrPCOE in ADMSCs)/B4(PrPCOE in ADMSCs+LPS). Sprague-Dawley (SD) rats (n = 50) were equally categorized into groups 1 (sham-operated-control)/2 (IR)/3 (IR+ADMSCs/6.0 × 105 equally divided into bilateral-renal arteries and 6.0 × 105 intravenous administration by 1 h after IR)/4 [IR+PrPCOE-ADMSCs (identical dosage administered as group 3)]/5 [IR+silencing PRNP -ADMSCs (identical dosage administered as group 3)], and kidneys were harvested post-day 3 IR injury. Results: Part I results demonstrated that the cell viability at 24/48/72 h, BrdU uptake/number of mitDNA/APT concentration/mitochondrial-cytochrome-C+ cells and the protein expressions of ki67/PrPC at 72 h-cell culturing were significantly higher in PrPCOE-ADMSCs than in ADMSCs (all P < 0.001). The protein expressions of oxidative-stress (NOX-1/NOX2/NOX4/oxidized protein)/mitochondrial-damaged (p22-phox/cytosolic-cytochrome-C)/inflammatory (p-NF-κB/IL-1ß/TNF-α/IL-6)/apoptotic (cleaved caspase-3/cleaved-PARP) biomarkers were lowest in A1/A3 and significantly higher in A2 than in A4 (all P < 0.001). Part II result showed that the protein expressions of inflammatory (p-NF-κB/IL-1ß/TNF-α/IL-6)/apoptotic (cleaved caspase-3/cleaved-PARP) biomarkers exhibited an identical pattern of part I among the groups (all P < 0.001). The protein expressions of inflammatory (p-NF-κB/IL-1ß/TNF-α/MMP-9)/oxidative-stress (NOX-1/NOX-2/oxidized-protein)/mitochondrial-damaged (cytosolic-cytochrome-C/p22-phox)/apoptotic (cleaved caspase-3/cleaved-PARP/mitochondrial-Bx)/autophagic (beclin-1/ratio of LC3B-II/LC3B-I)/fibrotic (Smad3/TGF-ß) biomarkers and kidney-injury-score/creatinine level were lowest in group 1, highest in group 2, significantly higher in group 5 than in groups 3/4 (all P < 0.0001). Conclusion: PrPCOE in ADMSCs rejuvenated these cells and played a cardinal role on protecting the kidney against IR injury.

Prevalence of accessory renal artery and other renal artery variants in south Indian population by CT-Angiography

The most frequent anatomical variations of the renal arterial system are accessory renal arteries (supernumerary renal arteries) and aberrant renal arteries, which occur in varying numbers among various ethnic and racial groups. Prior to surgery, understanding these variations is crucial because it affects the decision to use donor kidneys, the planning of partial nephrectomy, and other urological procedures. Along with the main renal artery on the same side, there is also an accessory renal artery. The aberrant artery supplies the kidney without passing through the hilum, whereas the main renal artery enters the kidney through the hilum to do so.Aim: This tertiary care hospital-based study aims to know the prevalence of variations of the renal arterial system including accessory renal artery, their distribution pattern, and association with gender, age, and side predilection in population of Kancheepuram and West Chennai district of Tamil Nadu.Methodology: One hundred adults (62 males, 38 females; mean age: 45 +/- 25 years) inclusive of prospective live renal donors undergoing pre-operative CT renal angiogram for operative planning and other patients undergoing CECT Abdomen for various abdomino-pelvic pathologies were selected for the study.Research Design: It is a cross-sectional descriptive study conducted in the Department of Radiology, of a tertiary care hospital in Kancheepuram district of Tamil Nadu, India.Results: Renal artery variants (including Accessory renal and aberrant renal arteries) are present in 23% of kidneys. The prevalence of renal artery variants in males – is 30%, and in females – 11%. On the right side the prevalence is 60% and on the left side is 26%. The prevalence of bilateral renal artery variants is 11%.

PS-BPR02-9: RECURRENCE OF RENAL ARTERY STENOSIS BY PONATINIB, A MULTI-TARGETED TYROSINE-KINASE INHIBITOR

Introduction: Cardiovascular disease and drug induced hypertension have been reported with tyrosine-kinase inhibitor including ponatinib treatment in chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). We report bilateral renal artery stenosis (RAS) in a patient who had received ponatinib for relapsing Ph+ALL after 2nd allogeneic stem cell transplantation. Case: A patient was a 40-year-old woman with no history of cardiovascular disease and hypertension. She developed myocardial damage that appeared to be ponatinib -induced, and catheterization of the heart revealed multiple coronary artery lesions and started optical medical therapy. 16 months after ponatinib treatment, she was referred to the nephrology department for evaluation of hypertension and increase in serum creatinine from 1.47 to 2.02 mg/dL. Renal ultrasonography and MRI revealed significant stenosis of the right renal artery, and angiography and stenting were performed. 5 months after the stent treatment, progression of renal dysfunction due to exacerbated RAS was observed. Intravascular ultrasonography revealed diffuse intimal thickening occurred in-stent restenosis, and balloon dilation was performed. She required balloon dilatation a total of three times even after the discontinuation of ponatinib treatment. The patient was thought to have systemic vascular endothelial damage caused by ponatinib. Discussion: It should be considered when hypertension and renal dysfunction occurs after ponatinib use

An easily misdiagnosed and rare cause of traumatic back pain: bilateral renal infarction caused by traumatic bilateral renal artery dissection.

An easily misdiagnosed and rare cause of traumatic back pain: bilateral renal infarction caused by traumatic bilateral renal artery dissection.

Percutaneous Transluminal Renal Angioplasty for Fibromuscular Dysplasia and Prognostic Risk Factors: A Retrospective Chinese Cohort Study

Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory vascular disease involving small-to-medium-sized arteries. The characteristics of Chinese patients with FMD remain unclear. We retrospectively analyzed the data of patients with renal FMD who underwent percutaneous transluminal renal angioplasty (PTRA) for the first time at Fuwai Hospital between 2010 and 2021. The variables were selected through least absolute shrinkage and selection operator regression (LASSO), and logistic regression models were constructed to identify independent risk factors. A total of 116 patients (52 males, median age at diagnosis, 25.0 years) were enrolled. Elevated blood pressure was the leading complaint. After a median follow-up period of 18.0 months (interquartile range: 6.0-48.0 months), hypertension recurred in 34 patients and restenosis in nine patients, among whom four patients underwent secondary intervention and one patient underwent surgical revascularization. Bilateral renal artery involvement (odds ratio [OR]: 2.61, 95% confidence interval [CI]: 1.11-6.15; p = 0.028) and age at hypertension onset (OR: 0.93, 95% CI: 0.88-0.99; p = 0.018) were independent prognostic factors for adverse outcomes. The results indicate that patients with bilateral renal artery involvement and younger age at hypertension onset are more likely to have poorer clinical outcomes after PTRA, and should be more closely monitored.

169: SITOSTEROLEMIA PRESENTING WITH SEVERE HYPERTENSION AND CONGESTIVE HEART FAILURE IN A CHILD

Introduction: Sitosterolemia is an autosomal recessive condition caused by pathogenic variants in the ABCG5/ABCG8 genes that prohibit the body from excreting plant sterols, causing build-up in the soft tissues and systemic vasculature. Pediatric vasculopathy secondary to sitosterolemia is poorly described, and there is no clear guidance on the management of complications, including cardiac dysfunction. This case report describes the diagnosis and acute management of a child with severe systemic hypertension, multiple levels of arterial stenosis, and cardiomyopathy presenting in congestive heart failure and ultimately diagnosed with sitosterolemia. Description: An 8-year-old Amish male with no past medical history presented to the emergency department with emesis and associated fatigue and abdominal pain. Vital signs were significant for severe systemic hypertension (BP 220/110), a gallop rhythm, hepatomegaly, cardiomegaly, and mid-aortic narrowing on CT angiogram. Exam was also notable for bilateral knee xanthomas. Laboratory data after admission to the pediatric cardiac ICU showed elevated BNP (peak 4418 pg/mL) and total cholesterol (317 mg/dL) levels. Echocardiogram showed severe mitral and tricuspid valve regurgitation, severely dilated and concentrically hypertrophied and dysfunctional left ventricle, ejection fraction of 30%, and pulmonary hypertension. Consultations included genetics, cardiology, nephrology, and vascular surgery. Initial management included a continuous Milrinone infusion and loop diuretics with improved BP and congestive heart failure symptoms. Cardiac catheterization including coronary and renal angiograms demonstrated severe proximal right coronary artery stenosis and bilateral renal artery stenosis. Right coronary artery and left renal artery angioplasties were performed with good results, and showed significant improvement in parameters of ventricular function and pulmonary arterial hypertension. Genetic testing and positive serum plant sterols confirmed the diagnosis of sitosterolemia. Discussion: Sitosterolemia is a rare genetic disorder and a rare cause of pediatric arteriopathy. Early recognition can prevent the development of life-threatening systemic hypertension, arterial stenosis including coronary artery disease, and cardiomyopathy.