Vasa Recta Research Articles

Pre-operative visceral adipose tissue radiodensity is a potentially novel prognostic biomarker for early endoscopic post-operative recurrence in Crohn's disease.

Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence (POR) of Crohn's disease (CD). However, its prognostic value is uncertain, in part, due to difficulties studying it non-invasively. To evaluate the prognostic value of pre-operative radiographic mesenteric parameters for early endoscopic POR (ePOR). We conducted a retrospective cohort study of CD subjects ≥ 12 years who underwent ileocecal or small bowel resection between 1/1/2007 to 12/31/2021 with computerized tomography abdomen/pelvis ≤ 6 months pre-operatively and underwent ileocolonoscopy ≤ 15 months post-operatively. Visceral adipose tissue (VAT) volume (cm3), ratio of VAT:subcutaneous adipose tissue (SAT) volume, VAT radiodensity, and ratio of VAT:SAT radiodensity were generated semiautomatically. Mesenteric lymphadenopathy (LAD, largest lymph node > 10 mm) and severe vasa recta (VR) engorgement (diameter of the VR supplying diseased bowel ≥ 2 × VR supplying healthy bowel) were derived manually. The primary outcome was early ePOR (Rutgeert's score ≥ i2 on first endoscopy ≤ 15 months post-operatively) and the secondary outcome was ePOR severity (Rutgeert's score i0-4). Regression analyses were performed adjusting for demographic and disease-related characteristics to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI). Of the 139 subjects included, 45% of subjects developed early ePOR (n = 63). VAT radiodensity (aOR 0.59, 95%CI: 0.38-0.90) and VAT:SAT radiodensity (aOR 8.54, 95%CI: 1.48-49.28) were associated with early ePOR, whereas, VAT volume (aOR 1.23, 95%CI: 0.78-1.95), VAT:SAT volume (aOR 0.80, 95%CI: 0.53-1.20), severe VR engorgement (aOR 1.53, 95%CI: 0.64-3.66), and mesenteric LAD (aOR 1.59, 95%CI: 0.67-3.79) were not. Similar results were observed for severity of ePOR. VAT radiodensity is potentially a novel non-invasive prognostic imaging marker to help risk stratify CD patients for POR.

Abstract P124: Piezo1 Mediates Vasodilation Induced By Acute Hyperglycemia In Mouse Renal Arteries And Microvessels

Background: Acute hyperglycemia (HG) is a risk factor for developing acute kidney injury and poor renal outcome in critically ill patients. The role of renal vasculature in this context is not clear. We hypothesize that HG-associated hyperosmolarity facilitates vasodilation through Piezo1-mediated eNOS activation. Methods: Vasoreactivity of isolated mouse mesenteric (MA) and renal interlobar (ILA) arteries were analyzed using wire myography and that of renal afferent (AA) and efferent (EA) arterioles, and vasa recta (VR) using microvascular perfusion. Immunofluorescence and western blot were used for molecular analyses of isolated mouse blood vessels as well HUVECs. Results: Pre-treatment with HG (44 mmol L -1 glucose; 4 h) increased acetylcholine (ACh)-induced relaxation in ILA and MA, which was prevented by eNOS inhibition using L-NAME. Hyperosmotic mannitol solution had a similar effect. HG induced an immediate, L-NAME-inhibitable dilation in AA, EA, and VR, whereby stronger dilation in AA compared to EA. HG also increased glomerular filtration rate in mice. In HUVECs, HG and the Piezo1 activator Yoda1 increased levels of Piezo1 protein, phosphorylated CaMKII (p-CaMKII), Akt, and p-eNOS. The HG-effect could be prevented by inhibiting Piezo1 using GsMTx4 and CaMKII using KN93. Furthermore, in arteries and microvessels, inhibition of Piezo1 using GsMTx4 prevented the HG-effect, while Yoda1 caused relaxation and dilation, respectively. Conclusion: Results reveal that Piezo1 mediates renal vasodilation induced by hyperosmolarity in acute HG. This mechanism may contribute to the pathogenesis of renal damage by acute HG.

Piezo1 Mediates Vasodilation Induced by Acute Hyperglycemia in Mouse Renal Arteries and Microvessels.

Acute hyperglycemia is a risk factor for developing acute kidney injury and poor renal outcome in critically ill patients, whereby the role of renal vasculature remains unclear. We hypothesize that hyperglycemia-associated hyperosmolarity facilitates vasodilation through Piezo1-mediated eNOS (endothelial NO synthase) activation. Vasoreactivity was analyzed using wire myography in isolated mouse mesenteric arteries and renal interlobar, and using microvascular perfusion in renal afferent arterioles and efferent arterioles, and vasa recta. Immunofluorescence and Western blot were used for molecular analyses of isolated mouse blood vessels and human umbilical vein endothelial cells. Pretreatment with hyperglycemia (44 mmol/L glucose; 4 hours) increased acetylcholine-induced relaxation in interlobar arteries and mesenteric arteries, which was prevented by eNOS inhibition using Nω-nitro-L-arginine methylester hydrochloride. Hyperosmotic mannitol solution had a similar effect. Hyperglycemia induced an immediate, Nω-nitro-L-arginine methylester hydrochloride-inhibitable dilation in afferent arterioles, efferent arterioles, and vasa recta, whereby stronger dilation in afferent arterioles compared to efferent arterioles. Hyperglycemia also increased glomerular filtration rate in mice. In human umbilical vein endothelial cells, hyperglycemia, and the Piezo1 activator Yoda-1 increased levels of Piezo1 protein, p-CaMKII (phosphorylated Ca2+/Calmodulin-dependent protein kinase type II), Akt, and p-eNOS (phosphorylated eNOS). The hyperglycemia effect could be prevented by inhibiting Piezo1 using GsMTx4 (Grammostola spatulata mechanotoxin 4) and CaMKII using KN93. Furthermore, in arteries and microvessels, inhibition of Piezo1 using GsMTx4 prevented the hyperglycemia -effect, while Yoda-1 caused relaxation and dilation, respectively. Results reveal that Piezo1 mediates renal vasodilation induced by hyperosmolarity in acute hyperglycemia. This mechanism may contribute to the pathogenesis of renal damage by acute hyperglycemia.

Interpretation and clinical utility of indocyanine-green fluorescence imaging (IFI) in robot-assisted anorectal-function saving operations (ASOs): A propensity-score matched analysis of 872 prospectively enroled patients undergoing IFI.

This study suggested a novel physiological evaluation of indocyanine-green fluorescence imaging (IFI), and its utility associated with anastomotic leakage/stricture (AL/AS) and prognosis. This study focussed on the utility of IFI, comparing IFI+versus IFI- groups (n=878 vs. 339), optimised by propensity-score matching. After intravenous injection of indocyanine green, maximal perfusion was separately assessed at the vasa recta (VR) and colonic wall (CW), by determining intensities at the VR (VRI) and CW (CWI) and respective time. Although IFI did not significantly reduce either AL or AS, which occurred approximately 3-fold frequently in patients with lower than higher intensity of VRI. IFI was found as an independent parameter for both disease-free [DFS: hazard ratio (HR)=0.489; p=0.002] and overall survival (OS: HR=0.519; p=0.021). Although IFI did not significantly reduce AL/AS, IFI independently reduced 5-year systemic recurrence and increased 5-year DFS and OS.

PS-BPB10-6: THE RELATION BETWEEN PERICYTE DETACHMENT AND INTERSTITIAL FIBROSIS IN DAHL SALT-SENSITIVE HYPERTENSIVE (DAHLS) RATS

Background: Congestive heart failure produces the state of fluid volume overload, central venous pressure (CVP) elevation, and consequently renal venous pressure (RVP) elevation. We have recently developed a novel rat unilateral renal venous congestion model, in which ligation of the inferior vena cava between both renal veins artificially induced renal congestion in the left kidney only. In this model, pericyte detachment and pericyte-myofibroblast transition (PMT) around the vasa recta were involved in interstitial injury and fibrosis. Dahl salt-sensitive hypertensive (DahlS) rats on high salt diets exhibit hypertension, congestive heart failure, fluid volume overload, CVP and RVP elevation, and renal damage, considering to be a non-artificial renal congestion model. The relation, however, between renal interstitial injury and fibrosis, elevated RVP, and pericyte detachment in DahlS rats has not been reported. In the present study, we assessed the relation of pericyte detachment around the vasa recta and PMT with interstitial fibrosis in DahlS rats. Methods: Eight-week-old DahlS rats (Dahl/Mcwi) were divided into three groups: normal diet, 4% NaCl diet, and 8% NaCl diet groups, and their kidneys were analyzed after 2 weeks. Total mRNA and protein expression levels were quantified by real-time PCR and western blot, respectively. Tubulointerstitial damage and fibrosis were identified by histological analysis. Furthermore, we evaluated pericyte detachment around the vasa recta by low-vacuum scanning electron microscopy (LV-SEM). Results: The expression of KIM1, a tubulointerstitial damage marker; CNN1 and αSMA, interstitial fibrosis markers; and TAGLN, a smooth muscle protein22 and PMT marker; was significantly increased in a salt-dependent manner in DahlS rats. In histological analysis, hyperplasia of the extracellular matrix and renal tubular injury were detected in 4% and 8% NaCl diet groups. The positive area of PMT markers in the interstitial space around the vasa recta was also increased in the NaCl diet groups. Pericyte detachment from the vasa recta was observed in the NaCl diet groups by LV-SEM. Conclusions: Pericyte detachment and PMT are involved in tubulointerstitial injury and fibrosis of DahlS rats. Renal venous congestion and subsequent physiological changes could have a role in renal damage and fibrosis. Arterial hypertension has been emphasized for a long time in renal injury, and venous hypertension must also be focused on with the concept of renal congestion. Further understanding of this concept may lead to new therapeutic strategies for renal injury.

Aquaporins in Urinary System.

There are at least eight aquaporins (AQPs) expressed in the kidney. Including AQP1 expressed in proximal tubules, thin descending limb of Henle and vasa recta; AQP2, AQP3, AQP4, AQP5, and AQP6 expressed in collecting ducts; AQP7 expressed in proximal tubules; AQP8 expressed in proximal tubules and collecting ducts; and AQP11 expressed in the endoplasmic reticulum of proximal tubular epithelial cells. Over years, researchers have constructed different AQP knockout mice and explored the effect of AQP knockout on kidney function. Thus, the roles of AQPs in renal physiology are revealed, providing very useful information for addressing fundamental questions about transepithelial water transport and the mechanism of near isoosmolar fluid reabsorption. This chapter introduces the localization and function of AQPs in the kidney and their roles in different kidney diseases to reveal the prospects of AQPs in further basic and clinical studies.

231-LB: GLP-1 Promotes Cortical and Medullary Perfusion in Human Kidney and Maintains Tissue Oxygenation during Na Loading

Purpose: GLP-1 receptor agonism has shown beneficial cardiovascular effects which could include the kidneys. In the human kidney, the high GLP-1 extraction and its natriuretic effect depend on the GLP-1 receptor and is accompanied by suppression of angiotensin II, independent of changes in renal plasma flow. Preclinical data showed that angiotensin II constricts the vasa recta and lowers medullary perfusion. The current randomized, controlled study was designed to test the hypothesis that GLP-1 increases renal medullary perfusion in healthy humans. Methods: Healthy male participants (n=10, 27 ± 4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1-hour infusion of either GLP-1 (1.5 pmol/kg/min) or placebo together with infusion of 0.9% NaCl (750 mL/h) . Interleaved measurements of renal artery flow, oxygenation (R2*) , and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. Results: GLP-1 infusion increased medullary perfusion (32 ± 7%, p<0.001) and cortical perfusion (13 ± 4%, p<0.001) compared to placebo. Here, NaCl infusion decreased medullary perfusion (-5 ± 2%, p=0.007) while cortical perfusion remained unchanged. R2* values increased by 3 ± 2% (p=0.025) in the medulla and 4 ± 1% (p=0.008) in the cortex during placebo, indicative of decreased oxygenation but remained unchanged during GLP-1. Renal arterial blood flow was not altered significantly by either intervention. Conclusions: GLP-1 increases predominantly medullary but also cortical perfusion in healthy human kidneys and maintains oxygenation during NaCl-loading. In perspective, GLP-1 may exert protective effects against renal hypoperfusion and ischemia. Disclosure B. Haddock: n/a. B. L. Jensen: None. A. Asmar: None.

MO422: Strong Positive Association Between GFR and the Urine-To-Plasma Urea Concentration Ratio in Patients With Sickle Cell Disease. Possible Functional Meaning

Abstract BACKGROUND AND AIMS Sickle cell disease (SCD) induces a decline in urine concentration and progressive deterioration of kidney (K) function. Hyperfiltration is often observed before this decline, and plasma urea is low. Oral urea or hydroxyurea improves the condition of these patients (pts). These observations draw the attention to renal urea handling in SCD. Studies suggest that addition of urea into the loop of Henle may indirectly modify NaCl concentration at the macula densa and induce a rise in glomerular filtration rate (GFR) by depressing the tubule-glomerular feedback (TGF) [1]. The urine-to-plasma urea concentration ratio (U/P urea) is a novel marker associated with GFR and the progression of disease in ADPKD [2]. The present study addresses the relationship of U/P urea with GFR in SCD pts. METHOD A total of 184 homozygous SCD pts referred to our department were included. They underwent extensive evaluation including measured GFR (mGFR) (51Cr EDTA clearance) and plasma and 24-h urine chemistries. The association between mGFR and U/P urea was tested using univariate, and multivariate stepwise regression analyses. RESULTS Mean age was 35.6 ± 2.8 years (mean ± SD) and body mass index (BMI) 22.2 ± 0.3 kg/m2. Mean mGFR was 107 ± 3 ml/min x 1.73m2. Hyperfiltration was observed in 37% of pts. Urine volume (UV) 1.71 ± 0.75 L/24h. Urea excretion 267 ± 151 mmol/24h. In 13% of pts fractional excretion of urea (FEurea) exceeded 50%. U/P urea (42 ± 20) varied from 6 to 112. It was not associated with 24-h urea excretion but showed a negative association with UV (P < 0.007). mGFR was strongly and positively associated with U/P urea (r = 0.58, P < 0.0001) but not with U/P osmolarity (see Figure and Table). mGFR was also associated with U/P creatinine although more weakly (r = 0.266, p < 0.0001) and with BMI and negatively associated with age, MAP and serum creatinine (creat). After adjustment for U/P creat, the association between mGFR and U/P urea remained highly significant, whereas, after adjustment for U/P urea, the association between mGFR and U/P creat disappeared. In multivariate regression, mGFR remained strongly associated with U/P urea. CONCLUSION Our data show a strong association between mGFR and U/P urea that remains highly significant after multivariate analysis. i) This suggests that a specific estimated GFR equation for SCD patients including the U/P urea ratio could be clinically more relevant than CKD-EPI equations. ii) A specific mechanism may link GFR and intrarenal urea handling, as U/P urea but not U/P osmolarity appears to be involved. Urea could play a role, indirectly, in the regulation of GFR [1]. In SCD, the longer transit time of the blood in vasa recta may favour countercurrent exchanges and lead to a greater addition of urea in loops of Henle (increasing the U/P urea ratio) and thus increasing GFR by reducing TGF. Sickled red cells and resulting in slower blood flow in the medulla may selectively influence urea handling, participating in high FEurea and GFR often observed in SCD pts. iii) As is the case in ADPKD, more attention should be given to longitudinal studies to the relationship between U/P urea and kidney disease progression in SCD pts.

Renal Venous Clamping Exacerbates Outer‐Medullary Red Blood Cell Congestion during Ischemia in Male and Female WKY Rats

Despite receiving approximately 20% of cardiac output, the kidneys are highly susceptible to ischemic injury, which is most prominent in the renal outer medulla. Previous studies have suggested that vascular congestion may explain the susceptibility of this region to injury. Further, increased injury has been reported in models where the renal vein is occluded compared to the renal artery. The goal of the current study was to determine whether renal arterial versus venous clamping would alter the severity of red blood cell congestion in the outer medulla. We hypothesized that venous clamping would result in greater vascular congestion than arterial clamping due to continued inflow of arterial blood.Ischemia reperfusion (IR) surgeries were performed on male and female WKY rats (10‐14 weeks). For each animal, the renal artery for one kidney and renal vein for the other kidney were clamped for a period 15 (n=7 male, 6 female) or 45 (n= 6 male, 5 female) minutes. The kidneys (right or left) which received arterial or venous clamping were rotated for each animal. Following ischemia, the kidneys were excised while the clamps remained on the vessels, without reperfusion. Vascular congestion of the outer medulla was scored blinded on a scale of 0 (0% congestion) to 5 (100% congestion) in trichrome stained kidneys sections.We found that there was significantly greater congestion of red blood cells in both the vasa recta and outer‐medullary plexus with venous clamping when compared to arterial clamping for both 15 minutes (p=0.0008, p<0.0001, respectively) (Fig. A) and 45 minutes (p=0.0001, p<0.0001, respectively) (Fig. B). There was no significant effect of sex observed on degree of vascular congestion regardless of the location or duration of the clamp.Our data indicates that red blood cell congestion is exacerbated by renal venous occlusion, which may explain the increased tubular injury that has been observed in this model. Therefore, future studies will investigate injury following recovery from renal artery versus vein clamping. Understanding the cause(s) of vascular congestion is essential for the development of clinically effective treatment options for acute kidney injury. Novel therapeutic approaches that prevent or reverse red blood cell congestion of the renal medulla may be effective in limiting ischemic acute kidney injury.

Transverse Colon Diverticulitis

Diverticula are small mucosal herniations protruding through the intestinal layers and smooth muscle along the natural openings created by the vasa recta or nutrient vessels in the wall of the colon. Diverticulitis of the transverse colon is a rare disorder which is often confused with other conditions and presents a challenge in diagnosis. We, here, report a case of transverse colon diverticulitis with mesocolic abscess treated surgically. This report increases awareness of this unusual condition.

Subcellular distribution of α2-adrenoceptor subtypes in the rodent kidney.

Renal α2-adrenoceptors have been reported to play a role in the regulation of urinary output, renin secretion, and water and sodium excretion in the kidneys. However, the distribution of α2-adrenoceptor subtypes in the kidneys remains unclear. In this study, we aimed to investigate the localization of α2-adrenoceptor subtypes in rat kidneys using 8-week-old Sprague-Dawley rats. Immunofluorescence imaging revealed that both α2A- and α2B-adrenoceptors were expressed in the basolateral, but not apical, membrane of the epithelial cells of the proximal tubules. We also found that α2A- and α2B-adrenoceptors were not expressed in the glomeruli, collecting ducts, or the descending limb of the loop of Henle and vasa recta. In contrast, α2C-adrenoceptors were found to be localized in the glomeruli and lumen of the cortical and medullary collecting ducts. These results suggest that noradrenaline may act on the basement membrane of the proximal tubules through α2A- and α2B-adrenoceptors. Moreover, noradrenaline may be involved in the regulation of glomerular filtration and proteinuria through the induction of morphological changes in mesangial cells and podocytes via α2C-adrenoceptors. In the collecting ducts, urinary noradrenaline may regulate morphological changes of the microvilli through α2C-adrenoceptors. Our findings provide an immunohistochemical basis for understanding the cellular targets of α2-adrenergic regulation in the kidneys. This may be used to devise therapeutic strategies targeting α2-adrenoceptors.

Renal allograft rejection with thrombotic microangiopathy associated with a Kidd blood group system alloantibody

Abstract Introduction/Objective The Kidd blood group antigens are urea transporters found on the surface of red blood cells, renal tubular epithelial cells, and endothelial cells in the renal medulla and vasa recta. While controversial, some reports have described an association between Kidd antigen donor/recipient mismatches and kidney transplant rejection when recipients possess or form anti-Kidd alloantibodies. To date, none of these reports have described development of a thrombotic microangiopathy (TMA) in the renal graft associated with these antibodies. We describe a case of fulminant renal transplant rejection associated with TMA in a patient with anti-Jk(a) alloantibodies who received a deceased-donor kidney transplant (DDKT). Methods/Case Report A 64-year-old woman with end-stage renal disease secondary to AL amyloidosis caused by plasma cell neoplasm received a DDKT associated with delayed graft function. No pre- or post-transplant donor specific antibodies (DSA) were detected, the flow crossmatch testing was negative, and a pre-operative type and screen identified anti-Jk(a) alloantibodies. On post-transplant day 5, her creatinine remained elevated at 6 mg/dL (ref range: 0.4–1.3 mg/dL) with an acute drop in platelets and undetectable haptoglobin. Allograft biopsy showed a combination of TMA with some additional evidence of acute cellular rejection. Tacrolimus was stopped to rule out drug-induced TMA, and the workup showed negative Shiga toxin, normal ADAMTS13 activity, negative atypical HUS genetic testing, and negative antiphospholipid syndrome testing. Genotyping of the donor kidney was positive for the Jk(a) antigen. Eculizumab, IVIG, and a trial of 8 sessions of therapeutic plasma exchange (TPE) were administered. Her creatinine improved (1.93–2.05 mg/dL), indicating a significant antibody-mediated etiology to her delayed graft function. About one month later, her creatinine worsened, and she received another trial of TPE with IVIG and eculizumab. Despite a mild decrease in her creatinine, repeat biopsies showed acute cellular rejection, persistent TMA, and chronic allograft injury. No DSAs were ever detected. Her creatinine never recovered, and she is now dialysis-dependent. Results (if a Case Study enter NA) NA Conclusion We speculate that anti-Jk(a) antibodies interacting with a Jk(a)-positive donor kidney account for graft TMA. This case underscores the potential importance of matching Kidd antigens in kidney transplantation.

TUBULOINTERSTITIAL INJURY WAS SUPPRESSED BY INHIBITION OF PLATELET-DERIVED GROWTH FACTOR PATHWAY IN RAT RENAL VENOUS CONGESTION MODEL

Objective: Increased central venous pressure in congestive heart failure is responsible for renal dysfunction. Pericytes contribute to the renal myofibroblast pool in renal fibrogenesis via pericyte-myofibroblast transition (PMT), and their detachment of from capillaries might trigger capillary rarefaction. We recently created a novel rat renal congestion model by ligation of the inferior vena cava (IVC) between the renal veins, resulting high renal interstitial hydrostatic pressure, tubulointerstitial injury and PMT. In this model, platelet-derived growth factor receptors (PDGFRs), which are PMT indicators, were upregulated. Thus we examined the effect of imatinib, a PDGFR inhibitor, for renal injury. Design and method: The inferior vena cava (IVC) between the renal veins was ligated by suture in male Sprague-Dawley rats to increase upstream IVC pressure and induce congestion only in the left kidney. Imatinib mesylate (20 mg/kg) or saline were injected intraperitoneally every day from one day before the operation. Both the right control kidney and the left congested kidney were obtained 3 days after the surgery and were weighted. The expression of renal injury marker and PDGFRs were assessed by quantitative reverse transcription-polymerase chain reaction, western blot and immunohistochemistry. The vascular structure of the kidneys was observed using micro-computed tomography (μCT) and low-vacuum scanning electron microscopy (LV-SEM). Results: Kidney weight was significantly increased in the left congested kidneys, and ameliorated by imatinib administration. However, μCT and LV-SEM results showed the maintained congestive state even in imatinib administration. Renal injury and fibrosis were observed in the congested kidneys, and imatinib significantly suppressed renal injury and fibrosis around the vasa recta. Conclusions: These results suggest that the inhibition of the PDGFRs pathway could suppress the renal fibrosis after PMT in heart failure-derived renal congestion. This mechanism could be a candidate therapeutic target for renoprotection against heart failure.

Ultraselective transcatheter arterial embolization with small-sized microcoils for acute lower gastrointestinal bleeding

PurposeTo evaluate the clinical outcome of ultraselective transcatheter arterial embolization (TAE) with small-sized microcoils for acute lower gastrointestinal bleeding (LGIB).Materials and methodsThe subjects were 17 consecutive patients (mean age, 69 years) with LGIB who were treated with ultraselective TAE using small-sized microcoils between December 2013 and December 2019. Ultraselective TAE was defined as embolization of one or both of the long or short branches of the vasa recta. The etiologies of bleeding were colonic diverticulosis in 16 patients (94%) and malignancy in one patient (6%). The bleeding foci were in the ascending colon in 11 patients (65%), transverse colon in 2 patients (12%), and sigmoid colon in 4 patients (23%). A total of 18 branches (diameter: range 0.5–1.5 mm, mean 1.1 mm) of the vasa recta in 17 patients were embolized with small-sized microcoils (size range 1–3 mm, mean combined lengths of all microcoils 7.6 cm). The mean follow-up period was 19 months (range 1–80 months). The technical and clinical success rate, recurrent bleeding rate, major complications and long-term clinical outcomes were retrospectively evaluated.ResultsTechnical and clinical success was achieved in all patients (17/17). The rates of early recurrent bleeding (within 30 days of TAE) and major complications were 0% (0/17). Recurrent bleeding occurred in one patient at 2 months after TAE, but was stopped with conservative treatment. There were no other bleeding episodes or complications in the follow-up period.ConclusionUltraselective TAE with small-sized microcoils is a highly effective and safe treatment modality for LGIB.

Pathological aspects of vasa recta fibrosis in kidney of dromedary camels

Pathological aspects of vasa recta fibrosis in kidney of dromedary camels

Natriuretic peptides relax human intrarenal arteries through natriuretic peptide receptor type-A recapitulated by soluble guanylyl cyclase agonists.

Natriuretic peptides, BNP and ANP increase renal blood flow in experimental animals. The signalling pathway in human kidney vasculature is unknown. It was hypothesized that BNP and ANP cause endothelium-independent relaxation of human intrarenal arteries by vascular natriuretic peptide receptor-A, but not -B and -C, which is mimicked by agonists of soluble guanylyl cyclase sGC. Human (n=54, diameter: 665±29µm 95% CI) and control murine intrarenal arteries (n=83, diameter 300±6µm 95% CI) were dissected and used for force recording by four-channel wire myography. Arterial segments were pre-contracted, then subjected to increasing concentrations of BNP, ANP, phosphodiesterase 5-inhibitor sildenafil, sGC-activator BAY 60-2770 and -stimulator BAY 41-2272. Endothelial nitric oxide synthase (eNOS) dependence was examined by use of L-NAME and eNOS knockout respectively. Molecular targets (NPR A-C, sGC, phosphodiesterase-5 and neprilysin) were mapped by PCR, immunohistochemistry and RNAscope. BNP, ANP, sildenafil, sGC-activation and -stimulation caused concentration-dependent relaxation of human and murine intrarenal arteries. BNP responses were independent of eNOS and were not potentiated by low concentration of phosphodiesterase-5-inhibitor, sGC-stimulator or NPR-C blocker. PCR showed NPR-A and C, phosphodiesterase-5, neprilysin and sGC mRNA in renal arteries. NPR-A mRNA and protein was observed in vascular smooth muscle and endothelial cells in arteries, podocytes, Bowmans capsule and vasa recta. NPR-C was observed in tubules, glomeruli and vasculature. Activation of transmembrane NPR-A and soluble guanylyl cyclase relax human preglomerular arteries similarly to phosphodiestase-5 inhibition. The human renal arterial bed relaxes in response to cGMP pathway.

Superselective transcatheter arterial embolization for acute small bowel bleeding: clinical outcomes and prognostic factors for ischemic complications.

Small bowel bleeding (SBB) accounts for 5%-10% of all cases of acute gastrointestinal bleeding. Transcatheter arterial embolization (TAE) plays an important role in the treatment of SBB. To evaluate the safety and efficacy of superselective TAE exclusively for SBB and to assess factors associated with clinical outcomes. From January 2006 to April 2017, 919 patients were admitted with signs and symptoms of gastrointestinal bleeding; 74 patients (mean age = 57.5 years; age range = 14-82 years) with positive angiographic findings for SBB were retrospectively analyzed. The technical success of TAE and clinical outcomes, including recurrent bleeding, major complications, and in-hospital mortality were evaluated. The associations of various clinical and technical factors with clinical outcomes were analyzed. The bleeding foci were in the ileum in 48 (65%) patients and the jejunum in 26 (35%). Technical success was achieved in 72 (97%) patients. The rates of recurrent bleeding, major complications, and in-hospital mortality were 12% (7/57), 21% (15/71), and 25% (18/72), respectively. Superselective embolization was a significant prognostic factor associated with fewer major complications (OR = 0.069; P = 0.003). The increased number of embolized vasa recta was significantly associated with a higher probability of major complications (OR = 2.64; P < 0.001). The use of N-butyl cyanoacrylate was associated with lower rates of major complication (OR = 0.257; P = 0.027). TAE is a safe and effective treatment modality for SBB. In addition, whenever possible, TAE should be performed in a superselective manner to minimize ischemic complications.

The distribution of the jejunal arteries in the cat.

The arterial supply of the cat jejunum was studied by gross dissection and polyurethane corrosion cast. The results showed that the jejunal arteries, which originate from the cranial mesenteric artery, varied from 5 to 15 in number. Their number was independent of the length of the cranial mesenteric artery as well as of the length of the jejunum. These arteries divided into branches giving rise to a series of orders of division from a minimum of 1 to a maximum of 7. The last orders of division terminated in a series of anastomosing arcades which resulted in a marginal artery coursing only a few millimeters from the mesenteric margin of the jejunum. This artery gave rise to straight arteries (vasa recta), whose mean number was 450 ± 60. According to their length, the vasa recta can be differentiated into short (vasa brevia) and long (vasa longa) branches. The vasa brevia ended branching into the mesenteric side of the jejunum whereas the vasa longa coursed beneath the serosa on the lateral jejunal surfaces, and reached the antimesenteric border. During their course, the vasa recta ramified and anastomosed with each other. Numerous antimesenteric anastomoses between opposing vasa longa were also observed. Based on the literature consulted, due to the large number of vasa recta (approximately one vessel per 2.9 mm of jejunal length) and the rich anastomotic network, the cat jejunum might have a better intramural distribution of blood flow and would seem less predisposed to ischemic phenomena than that of other mammals.

Renal microvasculature in the adult pipid frog, Xenopus laevis: A scanning electron microscope study of vascular corrosion casts.

We studied the opisthonephric (mesonephric) kidneys of adult male and female Xenopus laevis using scanning electron microscopy (SEM) of vascular corrosion casts and light microscopy of paraplast embedded tissue sections. Both techniques displayed glomeruli from ventral to mid‐dorsal regions of the kidneys with single glomeruli located dorsally close beneath the renal capsule. Glomeruli in general were fed by a single afferent arteriole and drained via a single thinner efferent arteriole into peritubular vessels. Light microscopy and SEM of vascular corrosion casts revealed sphincters at the origins of afferent arterioles, which arose closely, spaced from their parent renal arteries. The second source of renal blood supply via renal portal veins varied interindividually in branching patterns with vessels showing up to five branching orders before they became peritubular vessels. Main trunks and their first‐ and second‐order branches revealed clear longish endothelial cell nuclei imprint patterns oriented parallel to the vessels longitudinal axis, a pattern characteristic for arteries. Peritubular vessels had irregular contours and were never seen as clear cylindrical structures. They ran rather parallel, anastomosed with neighbors and changed into renal venules and veins, which finally emptied into the ventrally located posterior caval vein. A third source of blood supply of the peritubular vessels by straight terminal portions of renal arteries (vasa recta) was not found.

Ischemia‐induced vascular congestion of the ascending vasa recta precedes congestion of the peritubular capillaries in the renal medulla

Vascular congestion, or the aggregation of red blood cells in the microvasculature of the renal medulla is a prominent finding in ischemic acute kidney injury (AKI). Studies in rodent models of ischemia‐reperfusion injury (IRI) have suggested that vascular congestion occurs during the ischemic period and worsens following reperfusion, however, the location(s) in which congestion originates during ischemia have not been defined. We hypothesized that ‘vascular congestion first occurs in the medullary vasa recta (VR) capillaries during the ischemic period, prior to congestion of peritubular (PT) capillaries during reperfusion’. To test this hypothesis, a 45‐minute warm bilateral ischemia was performed in male WKY rats (10 wks old). Rats were randomized to 0, 1, 2, 6, 10, or 24 hour(s) of reperfusion (n=5/group). Congestion of the cortical PT capillaries, medullary VR and PT capillaries, and inner medulla (IM) was scored (blinded; scale: 0–5, 0=0% congestion, 5=100% congestion) in histological sections. To localize congestion within the VR, immunofluorescence of neural‐glial antigen 2 (NG2) was assessed. Medullary VR congestion score was 4.5 (90%) at time 0 (no reperfusion) and remained elevated at 1–10 hours of reperfusion. At 24 hours of reperfusion, VR congestion had significantly decreased to 30% (pANOVA= 0.004, post hoc p=0.002). Medullary PT congestion score was 0.5 (10%) at time 0 and was significantly less than the VR congestion at time 0 (90%) (pINTERACTION=0.004, post hoc p&lt;0.0001). Non‐quantitative analysis of NG2 staining, localized congestion to the ascending VR. At time 0, IM congestion score was 0.5 (10%). IM congestion increased to 4 (80%) by 2 hours of reperfusion (pANOVA=0.022, post hoc p=0.019) and remained elevated through 10 hours of reperfusion, however by 24 hours of reperfusion IM congestion had decreased. Congestion of the cortical PT capillary congestion was significantly greater at time 0 and had an average score of 2.5 (50%) (pANOVA=0.0005). Following 1, 2, or 6 hour reperfusion, cortical PT congestion decreased to less than 10%, and with 10 or 24 hour reperfusion there was no cortical congestion. It has been reported that congestion occurs during ischemia and increases following reperfusion, however the localization of medullary congestion over the initial 24 hours of reperfusion remains unknown. Importantly, our data provides the first evidence that medullary congestion originates in the VR capillaries during the ischemic period and is evident prior to congestion in the PT capillaries during reperfusion. Pericytes are contractile cells which surround the descending vasa recta (DVR). Using a pericyte marker, NG2, we found that congestion was not in NG2‐positive DVR but was localized to the ascending VR (NG2‐negative). Vascular congestion of the renal medulla has been reported to be the primary factor contributing to non‐recovery from ischemic AKI. Understanding how, and where, congestion occurs in the renal medulla is critical to find therapeutic targets for congestion in order to improve recovery from ischemic AKI. We speculate that medullary congestion of AVR may drive blood into the PT capillaries during reperfusion where it then becomes trapped which may prolong ischemia and worsen injury.Support or Funding InformationNIH PO1HL134604 and DK099548