Altered immune cell phenotypes within chronically ischemic human kidneys distal to occlusive renal artery disease.

Renal artery stenosis (RAS) is a major cause of ischemic kidney disease, which is largely mediated by inflammation. Mapping the immune cell composition in ischemic kidneys might provide useful insight into the disease pathogenesis and uncover therapeutic targets. We used mass cytometry (CyTOF) to explore the single-cell composition in a unique data set of human kidneys nephrectomized due to chronic occlusive vascular disease (RAS, n = 3), relatively healthy donor kidneys (n = 6), and unaffected sections of kidneys with renal cell carcinoma (RCC, n = 3). Renal fibrosis and certain macrophage populations were also evaluated in renal sections. Cytobank analysis showed in RAS kidneys decreased cell populations expressing epithelial markers (CD45-/CD13+) and increased CD45+ inflammatory cells, whereas scattered tubular-progenitor-like cells (CD45-/CD133+/CD24+) increased compared with kidney donors. Macrophages switched to proinflammatory phenotypes in RAS, and the numbers of IL-10-producing dendritic cells (DC) were also lower. Compared with kidney donors, RAS kidneys had decreased overall DC populations but increased plasmacytoid DC. Furthermore, senescent active T cells (CD45+/CD28+/CD57+), aged neutrophils (CD45+/CD15+/CD24+/CD11c+), and regulatory B cells (CD45+/CD14-/CD24+/CD44+) were increased in RAS. RCC kidneys showed a distribution of cell phenotypes comparable with RAS but less pronounced, accompanied by an increase in CD34+, CD370+, CD103+, and CD11c+/CD103+ cells. Histologically, RAS kidneys showed significantly increased fibrosis and decreased CD163+/CD141+ cells. The single-cell platform CyTOF enables the detection of significant changes in renal cells, especially in subsets of immune cells in ischemic human kidneys. Endogenous pro-repair cell types in RAS warrant future study for potential immune therapy.NEW & NOTEWORTHY The single-cell platform mass cytometry (CyTOF) enables detection of significant changes in one million of renal cells, especially in subsets of immune cells in ischemic human kidneys distal to renal artery stenosis (RAS). We found that pro-repair cell types such as scattered tubular-progenitor-like cells, aged neutrophils, and regulatory B cells show a compensatory increase in RAS. Immune cell phenotype changes may reflect ongoing inflammation and impaired immune defense capability in the kidneys.

Molecular genetic evaluation of pediatric renovascular hypertension due to renal artery stenosis and abdominal aortic coarctation in neurofibromatosis type 1.

The etiology of renal artery stenosis (RAS) and abdominal aortic coarctation (AAC) causing the midaortic syndrome (MAS), often resulting in renovascular hypertension (RVH), remains ill-defined. Neurofibromatosis type 1 (NF-1) is frequently observed in children with RVH. Consecutive pediatric patients (N = 102) presenting with RVH secondary to RAS with and without concurrent AAC were prospectively enrolled in a clinical data base, and blood, saliva and operative tissue, when available, were collected. Among the 102 children, 13 were having a concurrent clinical diagnosis of NF-1 (12.5%). Whole exome sequencing was performed for germline variant detection, and RNA-Seq analysis of NF1, MAPK pathway genes and MCP1 levels were undertaken in five NF-1 stenotic renal arteries, as well as control renal and mesenteric arteries from children with no known vasculopathy or NF-1. In 11 unrelated children with sequencing data, 11 NF1 genetic variants were identified, of which 10 had not been reported in gnomAD. Histologic analysis of NF-1 RAS specimens consistently revealed intimal thickening, disruption of the internal elastic lamina and medial thinning. Analysis of transcript expression in arterial lesions documented an approximately 5-fold reduction in NF1 expression, confirming heterozygosity, MAPK pathway activation and increased MCP1 expression. In summary, NF-1-related RVH in children is rare but often severe and progressive and, as such, important to recognize. It is associated with histologic and molecular features consistent with an aggressive adverse vascular remodeling process. Further research is necessary to define the mechanisms underlying these findings.

Effect of Hypoxia Preconditioning on the Regenerative Capacity of Adipose Tissue Derived Mesenchymal Stem Cells in a Model of Renal Artery Stenosis.

Atherosclerotic renal artery stenosis (ARAS) is associated with irreversible parenchymal renal disease and regenerative stem cell therapies may improve renal outcomes. Hypoxia preconditioning (HPC) may improve the regenerative functions of adipose tissue-derived mesenchymal stem cells (AMSC) by affecting DNA 5-hydroxymethylcytosine (5hmC) marks in angiogenic genes. Here, we investigated using a porcine ARAS model, whether growth of ARAS AMSCs in hypoxia (Hx) versus normoxia (Nx) would enhance renal tissue repair, and comprehensively analyze how HPC modifies DNA hydroxymethylation compared to untreated ARAS and healthy/normal pigs (n=5 each). ARAS pigs exhibited elevated serum cholesterol, serum creatinine and renal artery stenosis, with a concomitant decrease in renal blood flow (RBF) and increased blood pressure (BP) compared to healthy pigs. Renal artery injection of either autologous Nx or Hx AMSCs improved diastolic BP, reduced kidney tissue fibrosis, and inflammation (CD3+ T-cells) in ARAS pigs. In addition, renal medullary hypoxia significantly lowered with Nx but not Hx AMSC treatment. Mechanistically, levels of epigenetic 5hmC marks (which reflect gene activation) estimated using DNA immunoprecipitation technique were elevated in profibrotic and inflammatory genes in ARAS compared with normal AMSCs. HPC significantly reduced 5hmC levels in cholesterol biosynthesis and oxidative stress response pathways in ARAS AMSCs. Thus, autologous AMSCs improve key renovascular parameters and inflammation in ARAS pigs, with HPC mitigating pathological molecular effects on inflammatory and profibrotic genes which may play a role in augmenting regenerative capacity of AMSCs.

Double kiss mini-crush technique to treat complex recurrent renal artery in-stent restenosis.

The double-kiss mini-crush (DKMC) technique has been successfully deployed in the past for the treatment of complex coronary lesions even for left main lesions. Our case report consists of a proof-of-principle that the DKMC technique can be successfully translated as well to the field of complex renal artery lesions. Insightful thinking out-of-the "coronary" box in concert with skillful off-label application of coronary stenting procedures may open the gate for unprecedented opportunities for the treatment of difficult-to-tackle in-stent restenosis in the renal circulation.

Interventions for renal artery stenosis: Appraisal of novel physiological insights and procedural techniques to improve clinical outcome.

Randomized clinical trials failed to show additional benefit of renal artery stenting on top of medical therapy. Instead of writing an obituary on renal artery stenting, we try to explain these disappointing results. A transstenotic pressure gradient is needed to reduce renal perfusion and to activate the renin-angiotensin-aldosterone system. In only a minority of patients included in trials, a transstenotic pressure gradient is measured and reported. Like the coronary circulation, integration of physiological lesion assessment will allow to avoid stenting of non-significant lesions and select those patients that are most likely to benefit from renal artery stenting. Renal artery interventions are associated with peri-procedural complications. Contemporary techniques, including radial artery access, no-touch technique to engage the renal ostium and the use of embolic protection devices, will minimize procedural risk. Combining optimal patient selection and meticulous technique might lead to a netto clinical benefit when renal artery stenting is added to optimal medical therapy.

Percutaneous Transluminal Renal Angioplasty for Pediatric Hypertension Secondary to Total Renal Artery Occlusion.

PURPOSE: To assess the feasibility and effectiveness of percutaneous transluminal renal angioplasty (PTRA) for pediatric renovascular hypertension (RVH) secondary to total renal artery occlusion (RAO). MATERIALS AND METHODS: From 2011 to 2021, 13 pediatric patients with RVH confirmed with 14 renal artery occlusions were reviewed. The mean age was 11.2 years (range, 4-16 years). Nine occlusions involved main artery occlusion, and 5 involved branch occlusion. Blood pressure ratio (BPR) was defined as the ratio of the actual measured blood pressure (BP) value to the 95th percentile value adjusted for age, sex, and height. RESULTS: PTRA was performed in 9 patients (9/13, 69%). Technical success was achieved in 5 patients (5/9, 56%), with stent placement in 2 children (2/9, 22%). During the 12-month follow-up, restenosis was identified in both of the stent-receiving patients at the 12-month follow-up visit (2/9, 22%). Mean systolic BPR decreased from 1.20 (SD ± 0.07) to 0.96 (SD ± 0.06; P = .003), mean diastolic BPR decreased from 1.19 (SD ± 0.07) to 0.95 (SD ± 0.08; P = .005), and the number of medications required decreased from 3.8 (SD ± 0.8) to 2.4 (SD ± 0.9; P = .052) after PTRA. Subsequent to PTRA, the mean glomerular filtration rate of the occluded kidney improved from 19.5 mL/min (SD ± 12.3) to 36.3 mL/min (SD ± 10.8; P = .007), and the mean longitudinal dimension of the affected kidneys significantly increased from 8.2 cm (SD ± 1.5) to 9.2 cm (SD ± 1.7; P = .006). CONCLUSIONS: Endovascular treatment is often feasible for pediatric patients with RAO, results in acceptable BP control, and preserves renal function.

Patterns of cortical oxygenation may predict the response to stenting in subjects with renal artery stenosis: A radiomics-based model.

BACKGROUND: Percutaneous-transluminal renal angioplasty (PTRA) and stenting aim to halt the progression of kidney disease in patients with renal artery stenosis (RAS), but its outcome is often suboptimal. We hypothesized that a model incorporating markers of renal function and oxygenation extracted using radiomics analysis of blood oxygenation-level dependent (BOLD)-MRI images may predict renal response to PTRA in swine RAS. MATERIALS AND METHODS: Twenty domestic pigs with RAS were scanned with CT and BOLD MRI before and 4 weeks after PTRA. Stenotic (STK) and contralateral (CLK) kidney volume, blood flow (RBF), and glomerular filtration rate (GFR) were determined, and BOLD-MRI R2 * maps were generated before and after administration of furosemide, a tubular reabsorption inhibitor. Radiomics features were extracted from pre-PTRA BOLD maps and Robust features were determined by Intraclass correlation coefficients (ICC). Prognostic models were developed to predict post-PTRA renal function based on the baseline functional and BOLD-radiomics features, using Lasso-regression for training, and testing with resampling. RESULTS: Twenty-six radiomics features passed the robustness test. STK oxygenation distribution pattern did not respond to furosemide, whereas in the CLK radiomics features sensitive to oxygenation heterogeneity declined. Radiomics-based model predictions of post-PTRA GFR (r = 0.58, p = 0.007) and RBF (r = 0.68; p = 0.001) correlated with actual measurements with sensitivity and specificity of 92% and 67%, respectively. Models were unsuccessful in predicting post-PTRA systemic measures of renal function. CONCLUSIONS: Several radiomics features are sensitive to cortical oxygenation patterns and permit estimation of post-PTRA renal function, thereby distinguishing subjects likely to respond to PTRA and stenting.

Risks and benefits of renal artery stenting in fibromuscular dysplasia: Lessons from the ARCADIA-POL study.

INTRODUCTION: Although renal stenting is the standard revascularization method for atherosclerotic renal artery stenosis (RAS) (FMD-RAS), stenting in fibromuscular dysplasia (FMD) RAS is usually limited to periprocedural complications of angioplasty and primary arterial dissection. The main aim of the study was to retrospectively analyze the immediate and long-term results of renal stenting versus angioplasty in patients with FMD. METHODS: Of 343 patients in the ARCADIA-POL registry, 58 patients underwent percutaneous treatment due to FMD-RAS (in 70 arteries). Percutaneous transluminal renal angioplasty (PTRA) was performed as an initial treatment in 61 arteries (PTRA-group), whereas primary stenting was undertaken in nine arteries (stent-group). Stent-related complications were defined as: in-stent restenosis > 50% (ISR); stent fracture; under-expansion; or migration. RESULTS: In the PTRA-group, the initial restenosis rate was 50.8%. A second procedure was then performed in 22 arteries: re-PTRA (12 arteries) or stenting (10 arteries). The incidence of recurrent restenosis after re-PTRA was 41.7%. Complications occurred in seven of 10 (70%) arteries secondarily treated by stenting: two with under-expansion and five with ISR. In the stent-group, stent under-expansion occurred in one case (11.1%) and ISR in three of nine stents (33.3%). In combined analysis of stented arteries, either primarily or secondarily, stent-related complications occurred in 11/19 stenting procedures (57.9%): three due to under-expansion and eight due to ISRs. Finally, despite several revascularization attempts, four of 19 (21%) stented arteries were totally occluded and one was significantly stenosed at follow-up imaging. CONCLUSION: Our study indicates that renal stenting in FMD-RAS may carry a high risk of late complications, including stent occlusion. Further observational data from large-scale registries are required.

Renal Artery Reimplantation Versus Bypass in Elective Open Aneurysm Repair.

BACKGROUND: Complex open abdominal aortic aneurysm (AAA) repair often necessitates revascularization of renal arteries by either renal artery reimplantation or bypass. This study aims to evaluate the perioperative and short term outcomes between these 2 strategies of renal artery revascularization. METHODS: We performed a retrospective review of patients who underwent open AAA repair from 2004 to 2020 at our own institution. Patients who underwent elective suprarenal, juxtarenal, or type 4 thoracoabdominal aneurysm repair were identified using current procedural terminology (CPT) codes and a retrospectively maintained database of AAA patients. Patients who had symptomatic aneurysm or significant renal artery stenosis before AAA repair were excluded. Patient demographics, intraoperative conditions, renal function, bypass patency, and perioperative and postoperative outcomes at 30 days and 1 year were compared. RESULTS: One hundred and forty-three patients underwent either renal artery reimplantation (n = 86) or bypass (n = 57) during this time period. The mean age was 69.7 years and 76.2% of the patients were male. Median preoperative creatinine was 1.2 mg/dL for the renal bypass group versus 1.06 mg/dL for reimplantation (P = 0.088). Both groups had similar median preoperative glomerular filtration rate (GFR) of >60 mL/min (P = 0.13). Bypass and reimplantation groups had similar perioperative complications including acute kidney injury (51.8% vs. 49.4% P = 0.78), inpatient dialysis (3.6% vs. 1.2% P = 0.56), myocardial infarction (1.8% vs. 2.4% P = 0.99), and death (3.5% vs. 4.7% P = 0.99), respectively. During the 30-day follow-up period, renal artery stenosis was identified in 9.8% of bypasses and 6.7% of reimplantations (P = 0.71). Six point one percent of patients in the bypass group had renal failure requiring dialysis (both acute and permanent) compared to 1.3% in reimplantation group (P = 0.3). For those who had 1-year follow-up, the reimplantation group had higher new incidence of renal artery stenosis compared to bypass group (6 vs. 0 P = 0.16). CONCLUSIONS: Given that there is no significant difference in outcomes between renal artery reimplantation and bypass within 30 days or at 1-year follow-up, both bypass and reimplantation are acceptable means for renal artery revascularization during elective AAA repair.

A rare cause and an even rarer treatment of hypertension in a 5-year-old boy: Mid-aortic syndrome.

Renal artery stenosis is one of the common vascular diseases that cause hypertension in children. However, renal artery aneurysms and abdominal aortic aneurysms, which may be components of mid-aortic syndrome, are rarely associated with renal artery stenosis. Despite its rarity, early diagnosis and treatment are critical to prevent fatal complications. Currently, non-surgical invasive techniques are considered the first choice for treatment, but in some cases, surgery is inevitable. Here, we present a 5-year-old boy with a mid-aortic syndrome. The patient presented with a history of severe headache and epistaxis 5-6 times a day and was diagnosed with hypertension. A 9 × 9 mm saccular aneurysm on the anterior surface of the abdominal aorta at the level of the left renal artery ostium, and a 12 mm aneurysm in the left renal artery after a stenotic segment at the hilum level was detected in the doppler USG and contrast-enhanced imaging techniques. The patient was operated on electively. We used a PTFE patch to repair the abdominal aorta and, saphenous vein which was taken from his father to repair the renal artery. The patient recovered well and was discharged on the 18th day.

Clinical Practice Report of Contrast-Enhanced Ultrasound in Renal Artery Disease.

OBJECTIVES: To evaluate the diagnostic performance of renal artery contrast-enhanced ultrasound (CEUS) with modified inspection section and summarize subsequent changes in imaging assessment of renal artery disease. METHODS: A total of 1015 patients underwent renal artery CEUS were included in the study. Among them, 79 patients (156 renal arteries) suspected with renal artery stenosis (RAS) underwent digital subtraction angiography (DSA) subsequently. DSA was used as the gold standard to evaluate the diagnostic performance of CEUS in detecting RAS (≥30%) and severe stenosis (≥70%), as well as the diagnostic accuracy of classification of stenosis degree. Besides, 127 of the 1015 patients underwent other imaging examinations such as computed tomography angiography (CTA) or magnetic resonance angiography (MRA) after CEUS and annual proportion of these imaging examinations was assessed. RESULTS: The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of CEUS for detecting RAS (≥30%) was 96.4%, 88.6%, 94.2%, 95.6% and 90.7%, respectively and the kappa value was .857 (P < .01). CEUS had a good performance in distinguishing severe stenosis (≥70%) with a sensitivity of 91.1%, specificity of 95.5%, accuracy of 92.9%, PPV of 96.5%, NPV of 88.7% and the kappa value was 0.857(P < .01). There was no significant difference between CEUS and DSA in detecting stenosis (P = 1.0) and severe stenosis (P = .227). The diagnostic accuracy of CEUS in grading RAS was 85.3% and the kappa value was 0.753 (P < .01). Besides, the annual proportion of other imaging examinations decreased for 4 consecutive years. CONCLUSIONS: CEUS is a non-invasive, safe and valuable technique for the assessment of renal artery disease and worthy of promotion.

Deep-learning-based renal artery stenosis diagnosis via multimodal fusion.

PURPOSE: Diagnosing Renal artery stenosis (RAS) presents challenges. This research aimed to develop a deep learning model for the computer-aided diagnosis of RAS, utilizing multimodal fusion technology based on ultrasound scanning images, spectral waveforms, and clinical information. METHODS: A total of 1485 patients received renal artery ultrasonography from Peking Union Medical College Hospital were included and their color doppler sonography (CDS) images were classified according to anatomical site and left-right orientation. The RAS diagnosis was modeled as a process involving feature extraction and multimodal fusion. Three deep learning (DL) models (ResNeSt, ResNet, and XCiT) were trained on a multimodal dataset consisted of CDS images, spectrum waveform images, and individual basic information. Predicted performance of different models were compared with senior physician and evaluated on a test dataset (N = 117 patients) with renal artery angiography results. RESULTS: Sample sizes of training and validation datasets were 3292 and 169 respectively. On test data (N = 676 samples), predicted accuracies of three DL models were more than 80% and the ResNeSt achieved the accuracy 83.49% ± 0.45%, precision 81.89% ± 3.00%, and recall 76.97% ± 3.7%. There was no significant difference between the accuracy of ResNeSt and ResNet (82.84% ± 1.52%), and the ResNeSt was higher than the XCiT (80.71% ± 2.23%, p < 0.05). Compared to the gold standard, renal artery angiography, the accuracy of ResNest model was 78.25% ± 1.62%, which was inferior to the senior physician (90.09%). Besides, compared to the multimodal fusion model, the performance of single-modal model on spectrum waveform images was relatively lower. CONCLUSION: The DL multimodal fusion model shows promising results in assisting RAS diagnosis.

Graft survival after percutaneous transluminal renal stenting for transplant renal artery stenosis (TRAS) is worse compared to matched cadaveric grafts without TRAS.

OBJECTIVES: Transplant renal artery stenosis (TRAS) is now recognized as a curable disease with a good prognosis if intervention occurs in the early stage. However, the mid-term outcomes of TRAS when treated by percutaneous transluminal angioplasty with stent placement have yet to be fully elucidated. The purpose of this study was to compare mid-term graft and patient survival of TRAS group with a control group. PATIENTS AND METHODS: Ninety-two patients were diagnosed of TRAS between January 2016 and January 2022 in our center. Fifty-six pairs of recipients with grafts from the same donor were selected as a study group with TRAS and a control group without TRAS, respectively. All donor kidneys were from deceased organ donation rather than living donors. The primary endpoints were graft and patient survival. The secondary outcomes were changes in renal graft function. RESULTS: The mean follow-up time for the TRAS group was 43.6 months, while the mean follow-up time for the control group was 45.3 months. In the TRAS group, the age of patients ranged from 11 to 62 years with 39 males and 17 females. In the control group, the age of patients ranged from 18 to 67 years with 40 males and 16 females. In the TRAS group, there were more patients with diabetic nephropathy as the primary renal disease compared to the control group (5/56 vs 0/56), and the incidence of acute rejection was higher in the TRAS group than in the control group (12/56 vs 3/56). Eight patients in the TRAS group and one patient in the control group experienced graft loss (p = .019). Four patients in the TRAS group and four patients in the control group died with functional renal allograft during the follow-up time (p = .989). The levels of eGFR did not differ significantly between the two groups in the first three years after kidney transplant (p > .05). Patients in the TRAS group had worse graft functionality (eGFR, 44.96 ± 18.9 vs 54.9 ± 19.6 mL/min) in the fourth year when compared with the control group (p = .01). CONCLUSIONS: The graft function deteriorated faster, and graft survival was lower in the TRAS group treated by stent placement when compared with a control group without TRAS over the mid-term.

Effectiveness of contrast-enhanced duplex ultrasound for detecting renal artery stenosis: A systematic review.

PURPOSE: Contrast-enhanced duplex ultrasound (CEUS) might be a useful tool to diagnosing renal artery stenosis (RAS). We amalgamated and reviewed the evidence assessing the diagnostic accuracy of CEUS on detecting RAS compared to angiography. METHODS: This preregistered systematic review included studies that compared the presence of RAS via CEUS with angiography. Sources were searched in November 2022 and included Scopus, EMBASE, MEDLINE, CINAHL, and Academic Search Premier (n = 1717). The Quality Assessment of Diagnostic Studies 2 tool assessed study quality. Results are presented narratively. RESULTS: The studies included (n = 11) had a total of 447 unique participants (193 females) and average age of 56 ± 9 years. Five of eleven studies investigated CEUS using SonoVue contrast agent and reported an average accuracy (91% ± 2%), sensitivity (91% ± 3%), specificity (90% ± 5%), negative predictive value (86% ± 6%), and positive predictive value (94% ± 1%) with all values >80%. The accuracy of CEUS using other types of contrast agent (n = 6), including Levovsit (n = 3/6), Definity (n = 1/6), perfienapent emulsion (n = 1/6), and perfluorocarbon-exposed sonicated dextrose albumin (n = 1/6) was mixed. These studies detected an average accuracy of 91 ± 11% (n = 2/3% > 80%), sensitivity of 98% ± 4%, (n = 3/3% > 80%), and specificity of 86% ± 10% (n = 2/3% > 80%). Included studies had generally low risk of bias and applicability concerns except for unclear flow and timing (n = 7/11) and applicability of patient selection (n = 4/11). CONCLUSION: Despite being limited by the heterogeneity of included studies, our review indicates a high overall diagnostic accuracy for CEUS to detect RAS compared to angiography, with the largest evidence-base for SonoVue contrast. Radiologists and hospital decision makers should consider CEUS as an acceptable alternative to angiography.

Proximal Renal Artery Stenosis Presenting as Uncontrolled Hypertension.

Presentation: We present a case of 50-year-old lady who present with 1-month history of uncontrolled hypertension. Diagnosis: Magnetic resonance angiography showed stenosis of the left renal artery just beyond the ostium extending over approximately 7mm in length. Computed tomography angiography show focal narrowing of the proximal renal artery just distal to vessel origin, approximately 60% stenosis. Treatment: Anti-hypertensive medication was initiated in the ward. She was referred to vascular surgeon for renal bypass. Discussion: Renal artery stenosis is common cause of hypertension but may go unrecognised. The focus of this case is on the evaluation and necessity for a complete evaluation of the patient who is presenting with uncontrolled hypertension. To rule out renal artery stenosis, patient should be examined using CT-angiography or, if possible, arteriography.

[Kidney disease in antiphospholipid antibody syndrome]. / Manifestations rénales du syndrome des anticorps antiphospholipides.

Antiphospholipid syndrome (APS) is a rare autoimmune disease characterized by recurrent arterial and venous thromboembolic events. Renal complications occur in 3 % of patients. Renal artery stenosis is the most common, and APS-related nephropathy is the predominant microvascular complication. APS nephropathy has heterogeneous manifestations ranging from hematuria and non-nephrotic range proteinuria to hypertension and multi-organ failure caused by catastrophic antiphospholipid antibody syndrome. Anticoagulation and thromboprophylaxis are key to management. Immunosuppression has been used with some success but lacks randomized controlled trial validation for their use.

Le syndrome des anticorps antiphospholipides (SAPL) est une maladie auto-immune rare caractérisée par des événements thromboemboliques artériels et veineux récurrents. Les complications rénales surviennent chez 3 % des patients. La sténose de l'artère rénale est la plus courante et la néphropathie liée au SAPL représente la complication microvasculaire principale. La maladie rénale liée au SAPL se traduit par des manifestations hétérogènes allant de l'hématurie et de la protéinurie non néphrotique à l'hypertension jusqu'à la défaillance multi-organique causée par le syndrome catastrophique des anticorps antiphospholipides (SCAPL). L'anticoagulation et la thromboprophylaxie sont clés dans la prise en charge. L'immunosuppression a été utilisée avec un certain succès, mais manque de validation par des essais contrôlés randomisés pour leur utilisation.

Predicting renal function response to renal artery stenting.

OBJECTIVE: The Cardiovascular Outcomes in Renal Atherosclerotic Lesions Trial found no benefit of renal artery stenting (RAS) over medical therapy, although it was underpowered to detect a benefit among patients with chronic kidney disease (CKD). A post hoc analysis demonstrated improved event-free survival after RAS for patients whose renal function improved by 20% or more. A significant obstacle to achieving this benefit is the inability to predict which patients' renal function will improve from RAS. The objectives of the current study were to identify predictors of renal function response to RAS. METHODS: The Veteran Affairs Corporate Data Warehouse was queried for patients who underwent RAS between 2000 and 2021. The primary outcome was improvement in renal function (estimated glomerular filtration rate [eGFR]) after stenting. Patients were categorized as responders if the eGFR at 30 days or greater after stenting increased by 20% or more compared with before stenting. All others were nonresponders. RESULTS: The study cohort included 695 patients with a median follow-up of 7.1 years (interquartile range, 3.7-11.6 years). Based on postoperative change in eGFR, 202 stented patients (29.1%) were responders, and the remainder (n = 493 [70.9%]) were nonresponders. Before RAS, responders had a significantly higher mean serum creatinine, lower mean eGFR, and higher rate of decline of preoperative GFR in the months before stenting. After stenting, responders had a 26.1% increase in eGFR, compared with before stenting (P < .0001), which remained stable during follow-up. In contrast, nonresponders had a progressive 5.5% decrease in eGFR after stenting. Logistic regression analysis identified three predictors of renal function response to stenting: (1) diabetes (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.44-0.91; P = .013), (2) CKD stages 3b or 4 (OR, 1.80; 95% CI, 1.26-2.57; P = .001), and (3) rate of decline in preoperative eGFR per week before stenting (OR, 1.21; 95% CI, 1.05-1.39; P = .008). CKD stages 3b and 4 and the rate of decline in preoperative eGFR are positive predictors of renal function response to stenting, whereas diabetes is a negative predictor. CONCLUSIONS: Based on our data, patients in CKD stages 3b and 4 (eGFR 15-44 mL/min/1.73 m2) are the only subgroups with a significant probability of improved renal function after RAS. The rate of decline of preoperative eGFR over the months before stenting is a powerful discriminator of patients who are most likely to benefit from RAS. Specifically, patients with a more rapid decrease in eGFR before stenting have a significantly greater probability of improved renal function with RAS. In contrast, diabetes is a negative predictor of improved renal function, so interventionalists should be circumspect about RAS in diabetic patients.

Renal ischemia alters the transcriptomic and epigenetic profile of inflammatory genes in swine scattered tubular-like cells.

BACKGROUND: Scattered tubular-like cells (STCs) are differentiated renal tubular cells that during recovery from ischemic injury dedifferentiate to repair other injured renal cells. Renal artery stenosis (RAS), often associated with chronic inflammatory injury, compromises the integrity and function of STCs, but the underlying mechanisms remain unknown. We hypothesized that RAS alters the transcriptomic and epigenetic profile of inflammatory genes in swine STCs. METHODS: STCs were harvested from pig kidneys after 10 weeks of RAS or sham (n=6 each). STC mRNA profiles of inflammatory genes were analyzed using high-throughput mRNA-sequencing (seq) and their DNA methylation (5mC) and hydroxymethylation (5hmC) profiles by DNA immunoprecipitation and next-generation sequencing (MeDIP-seq) (n=3 each), followed by an integrated (mRNA-seq/MeDIP-seq) analysis. STC protein expression of candidate differentially expressed (DE) genes and common proinflammatory proteins were subsequently assessed in vitro before and after epigenetic (Bobcat339) modulation. RESULTS: mRNA-seq identified 57 inflammatory genes up-regulated in RAS-STCs versus Normal-STCs (>1.4 or <0.7-fold, P<0.05), of which 14% exhibited lower 5mC and 5% higher 5hmC levels in RAS-STCs versus Normal-STCs, respectively. Inflammatory gene and protein expression was higher in RAS-STCs compared with Normal-STCs but normalized after epigenetic modulation. CONCLUSIONS: These observations highlight a novel modulatory mechanism of this renal endogenous repair system and support development of epigenetic or anti-inflammatory therapies to preserve the reparative capacity of STCs in individuals with RAS.

Atherosclerotic renovascular disease: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and the Working Group Hypertension and the Kidney of the European Society of Hypertension (ESH).

Atherosclerotic renovascular disease (ARVD) is the most common type of renal artery stenosis. It represents a common health problem with clinical presentations relevant to many medical specialties and carries a high risk for future cardiovascular and renal events, as well as overall mortality. The available evidence regarding the management of ARVD is conflicting. Randomized controlled trials failed to demonstrate superiority of percutaneous transluminal renal artery angioplasty (PTRA) with or without stenting in addition to standard medical therapy compared with medical therapy alone in lowering blood pressure levels or preventing adverse renal and cardiovascular outcomes in patients with ARVD, but they carried several limitations and met important criticism. Observational studies showed that PTRA is associated with future cardiorenal benefits in patients presenting with high-risk ARVD phenotypes (i.e. flash pulmonary oedema, resistant hypertension or rapid loss of kidney function). This clinical practice document, prepared by experts from the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and from the Working Group on Hypertension and the Kidney of the European Society of Hypertension (ESH), summarizes current knowledge in epidemiology, pathophysiology and diagnostic assessment of ARVD and presents, following a systematic literature review, key evidence relevant to treatment, with an aim to support clinicians in decision making and everyday management of patients with this condition.

The Effect of Endovascular Treatment of Renal Artery Stenoses on Coexistent Aneurysms Associated with Fibromuscular Dysplasia.

PURPOSE: Endovascular data on patients with coexistent renal artery stenosis (RAS) and renal artery aneurysm (RAA) caused by fibromuscular dysplasia (FMD) are scarce, and the outcomes from RAS-specific treatment on RAA remain unclear. This study aimed to evaluate the safety and effectiveness of RAS-specific endovascular management in patients with coexisting RAA caused by FMD. MATERIALS AND METHODS: Clinical and endovascular data on 19 patients with coexistent RAS and RAA caused by FMD who underwent RAS-specific endovascular therapy were analyzed prospectively. An RAA located within 10 mm of the RAS was defined as a stenosis-related RAA (SRAA), and long-term outcomes were evaluated. RESULTS: Nineteen patients (24 RASs and 30 RAAs) underwent endovascular therapy. Twenty-one RASs were treated with balloon angioplasty alone, whereas 3 RASs were treated with stent implantation. None of the RAAs were treated directly. During an average of 4.2 years ± 3.2 of follow-up, systolic and diastolic blood pressures decreased from 183.0 mm Hg ± 19.5 and 120.2 mm Hg ± 19.0 to 127.9 mm Hg ± 10.3 and 80.9 mm Hg ± 6.9, respectively; the number of antihypertensive medications reduced from 1.7 ± 1.0 to 0.8 ± 0.3 (for all, P < .001). The serum creatinine level remained stable. The maximum diameter of all RAAs decreased from 14.6 mm ± 9.7 to 11.3 mm ± 8.4 (P < .001). There was a significant difference in the improvement rate of the maximum diameter between SRAAs (65.0%, 13 of 20) and non-SRAAs (20.0%, 2 of 10) (P = .019). CONCLUSIONS: RAS-specific endovascular therapy is safe and effective and possibly aids in preventing RAA progression in patients with FMD with coexistent RAS and RAA.