Vasa Recta Research Articles

Pretreatment with low dose lipopolysaccharide promotes rapid decongestion of medullary capillaries

Acute kidney injury (AKI) is common and has a mortality rate as high as 60%. Vascular congestion is a hallmark of AKI and is the aggregation of red blood cells (RBC) in the capillaries of the renal medulla following ischemia. Studies have shown that the severity of vascular congestion directly correlates with the recovery of renal function following ischemia. We recently reported that pretreatment with low dose lipopolysaccharide (LPS) attenuates vascular congestion following ischemia‐reperfusion injury (IRI) in rats. It remains unknown, however, if LPS prevents the formation of congestion or aids in the clearance of congestion following reperfusion. We hypothesized that ‘low dose LPS stimulates the clearance of RBC aggregates during early reperfusion’. To test this hypothesis, male WKY rats (10wks) were pretreated (i.p) with 1000μg/kg LPS (serotype O111:B4) or saline daily for 3 days. Following pretreatment, a 45‐minute warm, bilateral ischemia was performed. Rats were randomized to either 0, 1, 2, 6, 10, or 24 hour(s) of reperfusion (n=4/group). Following reperfusion, blood was collected for measurement of erythrocyte sedimentation rate (ESR). Congestion of the medullary vasa recta (VR) and peritubular (PT) capillaries was assessed in histological sections (blinded, scale: 0–5, 0=0% congestion, 5=100% congestion). Medullary VR congestion was not different between saline and LPS treated rats at time 0 (no reperfusion) with a score of 4 (80%) for both. Following reperfusion for 1, 2, 6, and 10 hours, VR congestion in saline treated rats remained elevated (average score: 4.09). In contrast, in LPS treated rats, VR congestion rapidly declined (within 1 hour), such that between 1–10 hours of reperfusion VR congestion averaged 1.89 (pTREATMENT<0.0001). PT congestion was minimal for both saline and LPS treated rats at time 0 (no reperfusion) but rapidly increased in saline treated rats to >60% at 6 hours. Conversely, in LPS treated rats PT congestion remained low (average 13.4%, pINTERACTION=0.0144) across the 24 hour reperfusion period. In saline treated rats, ESR, which is a marker of inflammation, was less than 2mm at 1–10 hours of reperfusion but increased to 7mm at 24 hours post‐ischemia. In LPS treated rats, ESR increased in a time dependent manner from 0mm at time 0 to 10mm at 24 hours (pTREATMENT<0.0001). We recently reported that pretreatment with LPS reduced vascular congestion 24 hours following ischemia‐reperfusion, however it was unclear whether LPS prevents the development of congestions or contributes to a quicker reperfusion. In this study, we tracked congestion following different hour(s) of reperfusion and found that LPS aids in flushing the VR following reperfusion which prevents the development of PT congestion. We speculate the early immune response evoked by LPS pretreatment, evident by ESR, is responsible for the rapid clearance of congestion in these animals. Understanding the mechanism by which LPS promotes this protective response to attenuate renal medullary congestion following ischemia may provide new methods to improve recovery and mortality rate from ischemic AKI.Support or Funding InformationNIH PO1HL134604 and DK099548

Regression of Peritubular Capillaries Coincides with Angiogenesis and Renal Cyst Growth in Experimental Polycystic Kidney Disease.

Background/AimThe natural history of the renal microvasculature changes in PKD is not known. The aim of this study was to test the hypothesis that angiogenesis is coupled with kidney cyst expansion, and the loss of peritubular capillary networks precedes the onset of interstitial fibrosis.MethodsThe renal microvasculature (RECA-1 and CD34) was evaluated in groups of Lewis polycystic kidney (LPK) rats and juvenile cystic kidney (jck) mice during the early, mid and late stage of disease. In addition, LPK rats and jck mice received sirolimus to determine if the reduction in renal cyst growth is in part mediated by the suppression of angiogenesis.ResultsIn LPK rats, the loss of peritubular capillaries occurred in early-stage disease and paralleled cyst formation whereas in jck mice it was delayed to the mid stage. In both models, vasa recta were displaced by growing cysts and regressed in LPK rats with disease progression but lengthened in jck mice. Cortical and medullary capillary neoangiogenesis occurred during the early stage in both models and persisted with progression. Treatment with sirolimus reduced cyst enlargement but did not alter the progression of renal microvasculature changes in either model.ConclusionRegression of peritubular capillaries and disruption of vasa recta occur in parallel with angiogenesis and the progressive enlargement of kidney cysts. These data suggest that the regrowth of peritubular capillaries together with inhibition of angiogenesis are potential strategies to be considered in the treatment of PKD.

Anatomical features in the kidney involved in water conservation through urine concentration in dromedaries (Camelus dromedarius)

The aim of this study was to report some of the morphological characteristics of the kidney involved in urine concentration and hence water conservation in the dromedaries. A total of 20 fresh kidneys of 10 apparently healthy camels were used in this study. The architecture of the renal pelvis was revealed by dissection and polyvinyl chloride corrosion casts. Samples were also processed for histology and for enzyme histochemistry. The camel kidney is bean shaped, smooth, multilobar, unipapillary, in which the fusion of renal papillae is complete forming a common renal papilla or crest, which channel urine into a central renal pelvis. It is more or less similar to equine, caprine, ovine and canine kidney. Under certain anatomical requisites the renal pelvis is known to play a role in urine concentration through recycling of urea to increase the medullary osmotic concentration which favors the counter-current mechanism. One of these requisites is an elaborate renal pelvis which is closely associated with the renal medulla. The renal pelvis of the camel has a main crescentic cavity following the long axis and curvature of the kidney. A thick extensive renal crest projects into the cavity of the pelvis. The thick renal crest contains large numbers of long loops of Henle and vasa recta which are important for urine concentration. The renal crest is formed by convergence of the medullary pyramids before it projects into the cavity of the renal pelvis. The crescentic main cavity of the pelvis forms 20–24 three dimensional radiating collateral recesses which contain the medullary pyramids. This close association of the renal pelvis and medulla provide a large surface area for the recycling of urea and hence urine concentration. This large pelvic-medullary interface is lined by simple low cuboidal epithelium which enhances the recycling of urea and water from the pelvic urine into the medulla and directly contributes to urine concentration. The rest of the wall of the renal pelvis and its recesses facing away from the renal crest and medullary pyramids is lined by impermeable transitional epithelium. Another feature is the intense activity of alkaline phosphatase demonstrated in the proximal convoluted tubules which indicates increased membrane transport. It is concluded that the kidney in dromedaries has the anatomical and histochemical requisites for the production of concentrated urine. These requisites enable the kidney to adequately contribute to the ability of the camel to conserve water and withstand the aridity of its habitat.

Effect of iodinated contrast media on the oxygen tension in the renal cortico-medullary region of pigs.

Repeated injections of iodinated contrast media (CM) can lead to a deterioration of the renal blood flow, can redistribute blood from the renal cortex to other parts of the kidney and can cause small decreases of the blood flow in cortical capillaries, a significant reduction in blood flow in peritubular capillaries and a significant reduction in blood flow in the vasa recta. Therefore, a study in pigs was designed, to show whether the repeated injection of CM boli, alone, can cause a reduction of oxygenation in the cortico-medullar renal tissue - the region with the highest oxygen demand in the kidney - of pigs.While the mean pO2-value had only decreased by 0.3 mmHg from 29.9±4.3 mmHg to 29.6±4.3 mmHg (p = 0.8799) after the tenth Iodixanol bolus, it decreased by 5.9 mmHg from 34.0±4.3 mmHg to 28.1±4.3 mmHg after the tenth Iopromide bolus (p = 0.044). This revealed a remarkable difference in the influence of these CM on the oxygen partial pressure in the kidney.Repeated applications of CM had a significant influence on the renal oxygen partial pressure. In line with earlier studies showing a redistribution of blood from the cortex to other renal areas, this study revealed that Iodixanol - in contrast to Iopromide - induced no changes in the pO2 in the cortico-medullar region which confirms that Iodixanol did not hinder the flow of blood through the renal micro-vessels. These results are in favor of a hypothesis from Brezis that a microcirculatory disorder might be the basis for the development of CI-AKI.

Serial Radiographic Imaging for Real-Time Evaluation of Blood Flow During Low Anterior Resection: Initial Study in a Porcine Model

To determine whether real-time intraoperative serial radiographic imaging of the marginal artery and vasa recta is feasible in patients undergoing low anterior resection, we attempted such imaging in a porcine model using a specialized fluoroscopic digital X-ray system and thin flat panel detector. Of the possible complications after low anterior resection, anastomotic dehiscence is one of the most serious, with poor blood supply in the anastomotic region being a chief contributor. General anesthesia was induced in a male domestic pig, and a midline incision was made from the xiphoid process to just above the bladder. The rectum was transected at the peritoneal reflection and then mobilized by dissection of the right leaf of the sigmoid mesocolon from the inferior mesenteric artery to the superior rectal artery. The rectal stump was pulled out and placed directly on the detector. Noniodine contrast agent was injected, and blood flow to and from the area surrounding the rectum was evaluated. Serial radiographs depicting the superior rectal artery, colonic, rectal, surrounding mesenteric tissue, and the vasa recta were obtained. The region where the marginal artery ran along the distal portion of the rectal stump was poorly poor imaged in all 3 imaging phases. Diameters of arteries were easily determined. The success we had in radiographically observing blood flow in tissues that would be involved in low anastomosis convinced us that such intraoperative evaluation is clinically feasible.

Feasibility and reliability of supermicrosurgical vasa recta anastomosis for double-pedicled free jejunum transfer

BackgroundAlthough free jejunal transfer is an established and reliable procedure for reconstruction after total pharyngolaryngectomy (TPL), vascular thrombosis remains a surgical challenge. To reduce the risk, a double-pedicled free jejunal flap transfer has been attempted using a root jejunal artery and an arcade artery, although several drawbacks exist. The vasa recta are terminal straight vessels that arborize from an arcade artery without branching. We present a novel double-pedicled free jejunum transfer using vasa recta anastomosis. MethodsBetween 2011 and 2015, we performed 14 double-pedicled free jejunal flap transfers for reconstruction after TPL. Vasa recta were used for second arterial anastomosis in 5 out of 14 patients. Others include a root artery in three patients and an arcade artery in six patients. Indocyanine green (ICG) angiography was performed to confirm the patency and perfusion of the entire flap by the second artery alone. ResultsThe flaps survived completely in all cases. The vasa recta (average diameter; 0.8 mm) were anastomosed to the superior thyroid artery and transverse cervical artery in four and one cases, respectively. Supramicrosurgical end-to-side anastomosis was performed in two cases. ICG angiography showed sufficient perfusion of the entire flap with the second artery alone in all cases. ConclusionAs vasa recta were confirmed as being capable of perfusing the entire flap up to 25 cm, the double-pedicle method using vasa recta might be an option to reduce the risk of flap necrosis, particularly in high-risk patients.

Abstract P127: Pericyte Detachment is Involved in Renal Congestion in a Novel Rat Model

Increased central venous pressure in congestive heart failure is responsible for renal dysfunction; however, the underlying mechanisms are unclear. We hypothesized that renal interstitial hydrostatic pressure (RIHP) and expansion pressures of the vasa recta are responsible for pericyte detachment resulting renal congestion-mediated fibrosis. We created a novel rat renal congestion model and investigated the effect of renal congestion on hemodynamics and its molecular mechanisms. 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 in the left kidney only. Left kidney congestion reduced renal blood flow in cortex (33.6%, 28.3 to 16.0 mL/min) and in medulla (41.8%, 11.9 to 6.9 mL/min) and glomerular filtration rate (1.16 to 0.20 mL/min/kg BW), and increased RIHP (12.6 to 17.6 mm Hg). Hypoxia was observed in the medullary thick ascending limb of Henle, only in the congestive kidneys. Tubulointerstitial injury, podocyte injury, albuminuria, and reduced creatinine clearance were observed in the congestive kidneys. Molecules related to extracellular matrix expansion, tubular injury, and focal adhesion were upregulated in microarray analysis. Renal decapsulation ameliorated the tubulointerstitial injury (mRNA expression of Kim1 15.3 to 4.3 A.U., αSma 5.3 to 2.8 A.U.). Electron microscopy captured pericyte detachment in the congestive kidneys. Transgelin and platelet-derived growth factor receptors (PDGFRs), as indicators of pericyte-myofibroblast transition, were upregulated in the pericytes and the adjacent interstitium. Imatinib, a PDGFR inhibitor, ameliorated the interstitial injury. Our results reveal a novel mechanism of worsening renal function associated with congestive heart failure, and provide a new therapeutic strategy based on a better understanding of the pericyte-myofibroblast transition.

Abstract P242: Effects of Proton Receptor Gpr4 Deficiency on Angiotensin Receptors in Kidney and Hindbrain

The proton receptor GPR4, a G protein-coupled receptor with protons as ligands, is abundant in the brain [subfornical organ (SFO) and paraventricular nucleus (PVN) of the hypothalamus], lung, and kidney. The receptor is activated in physiological pH range and GPR4 deletion is associated with chronic mild acidosis. The GPR4-/- mice exhibit ~15 mm Hg lower systolic blood pressure accompanied by ~50% lower angiotensin lower AT 1 receptors in SFO and PVN. We now report data for angiotensin receptor binding in the kidney and hindbrain using in vitro receptor autoradiography with 125 I-Sarthran as the ligand in GPR4-/- (n = 3 kidney, n = 4 hindbrain) and wild type (GPR4+/+, n = 3 kidney, n = 4 hindbrain) mice. GPR4-/- mice have lower 125 I-Sarthran specific maximal binding in the renal medullary region (43 ± 16 vs. 127 ± 20 fmol/mg protein in GPR4+/+; p = 0.03), which is the region with highest expression of GPR4. There was a trend for lower binding, although not significant, in the vasa recta area (78 ± 17 vs. 177 ± 46 fmol/mg protein in GPR4+/+; p = 0.12), glomeruli (414 ± 48 vs. 522 ± 17 fmol/mg protein in GPR4+/+; p = 0.10) and tubules (250 ± 44 vs. 350 ± 28 fmol/mg protein in GPR4+/+; p = 0.13). There were no differences in binding maximal density in brain medullary regions such as nucleus tractus solitarii (NTS), area postrema (AP), dorsal motor nucleus of the vagus (DMV) or olivary complex (OC). Non-specific binding was similar in GPR4+/+ and -/- mice in both kidney and brain. AT 1 receptors as defined by competition with losartan account for the majority of binding in each of the regions in mouse kidney (>70%), while the brain medullary binding exhibits ~50% AT 1 and AT 2 sites. Thus, GPR4 deletion lowers AT 1 receptors in tissues involved in control of blood pressure and fluid and electrolyte balance, such as forebrain nuclei and renal medullary regions where there is high abundance of both AT 1 and GPR4 receptors. Whether the down-regulation of the AT 1 receptor at these sites is a direct effect in response to loss of activation of the GPR4 or is secondary to the acid-base balance alterations in these animals is unknown. However, the lower blood pressure in the GPR4-/- mice supports the concept that the GPR4 receptor is a potential therapeutic target for lowering of pressure.

Diagnostic suggestion and surgical consideration for Hirschsprung’s disease associated with high anorectal malformation

Object: The objective of this study were to highlight the finding of vasa recta (tortuous) on the colonic wall as a diagnostic clue for suspecting an associated Hirschsprung’s disease (HD) and to draw attention to the importance of preserving the aganglionic rectum plus a retrorectal pull through in these cases. Background: The association of HD with anorectal malformation (ARM) is both diagnostically and surgically challenging. Patients and methods: Records of cases with ARM treated over 15 years were examined. Among these, five children with an associated HD were analyzed with regard to their clinical, radiological, surgical, histopathological findings, and outcome. Relevant literature was also reviewed. Results: HD was present in 1.26% cases of ARM. All were men with high-type ARM. Two groups were identified. In group 1 (two patients), associated HD was suspected after completion of all stages of ARM repair. They reported prolonged postoperative constipation, abdominal distention, and enterocolitis. Moreover, they endured additional surgeries for HD. In group 2 (three patients), HD was suspected at the time of initial colostomy for ARM in two patients on visualizing tortuous (cork screw) vasa recta on the sigmoid colon surface in a region similar to the transition zone in HD. Biopsy from the site confirmed HD. In the third patient, these vessels were visualized on the colostomy loop at the time of laparoscopic pull through for ARM. Preservation of the aganglionic rectum (to function as a fecal reservoir) as well as a retrorectal pull through was done in both groups. Conclusion: Finding prominent corkscrew vessels on the colonic surface could serve as a clinical clue for the presence of HD in cases of ARM. Moreover, preserving the aganglionic rectum and performing a Duhamel pull through helps provide acceptable continence. Keywords: anorectal malformation, Hirschsprung’s disease, rectal reservoir, tortuous vasa recta

Morphologic and morphometric study on microvasculature of developing mouse kidneys

A proper morphogenesis of the renal microvasculature is crucial not only for fulfilling the renal function but also to slow down the progression of chronic kidney disease in adulthood. However, the current description of the developing microvasculature is incomplete. The present study investigated the morphogenesis and volume densities of the renal microvasculature using computer-assisted tubular tracing, immunohistochemistry for CD34, and unbiased stereology. The earliest glomerular capillaries were observed at the lower cleft of the S-shaped nephrons, as simple loops connecting the afferent and efferent arterioles. In parallel with this, the peritubular capillaries were established. Noticeably, from early nephrogenesis on, the efferent arterioles of the early-formed glomeruli ran in close proximity to their own thick ascending limbs. In addition, the ascending vasa recta arising from the arcuate or interlobular veins also ran in close proximity to the thick descending limb. Thus, the tubules and vessels formed the typical countercurrent relation in the medulla. No loop bends were observed between descending and ascending vasa recta. The volume density of the cortical and medullary peritubular capillary increased 3.3- and 2.6-fold, respectively, from 2.34 (0.13) and 7.03 (0.09)% [means (SD)] at embryonic day 14.5 (E14.5) to 7.71 (0.44) and 18.27 (1.17)% at postnatal day 40 (P40). In contrast, the volume density of glomeruli changed only slightly during kidney development, from 4.61 (0.47)% at E14.5 to 6.07 (0.2)% at P7 to 4.19 (0.47)% at P40. These results reflect that the growth and formation of the renal microvasculature closely correspond to functional development of the tubules.

Immunohistochemistry of Vasohibin-2 in Human Kidney Disease : Implications in Impaired Glucose Tolerance and Reduced Renal Function.

Several angiogenesis-related factors are known to play important roles in the pathogenesis of kidney disease. Vasohibin-2 (VASH-2) was recently reported as a novel proangiogenic factor. Although VASH-2 was demonstrated to accelerate tumor angiogenesis, its roles in non-tumor processes including renal disease have not been well elucidated yet. Here, we performed a retrospective study including an immunohistochemical analysis of human kidney biopsy specimens from 82 Japanese patients with a variety of kidney diseases, and we evaluated the correlations between the immunoreactivity of VASH-2 and the patients' clinicopathological parameters. VASH-2 immunoreactivity was detected in varying degrees in renal tubules as well as in peritubular capillaries and vasa recta. The cortical and medullary tubule VASH-2+ scores were correlated with the presence of hypertension, and the medullary tubule VASH-2+ score was significantly correlated with the blood glucose (p=0.029, r=0.35) and hemoglobin A1c levels (p=0.0066, r=0.39). Moreover, decreased VASH-2+ scores in the vasa recta were associated with reduced renal function (p=0.0003). These results suggest that VASH-2 could play an important role in the pathogenesis of renal diseases, and that VASH-2 is closely associated with hypertension and impaired glucose tolerance.

Vasa recta pericyte density is negatively associated with vascular congestion in the renal medulla following ischemia reperfusion in rats.

Recent evidence suggests that a greater density of pericytes in renal cadaveric allografts is associated with better recovery following transplant. The physiological mechanism(s) through which pericyte density may be beneficial is not well understood. The goal of this study was to test the hypothesis that lower medullary pericyte density is associated with greater renal injury following ischemia reperfusion (IR) in a rat model, providing a basis for future studies to better understand pericytes in a pathological environment. To test our hypothesis, we determined the association between medullary pericyte density and renal injury in spontaneously hypertensive rats (SHR) following 45 min of warm bilateral IR. We found that there was a significant negative relationship between pericyte density and plasma creatinine (slope = -0.03, P = 0.02) and blood urea nitrogen (slope = -0.5, P = 0.01) in female but not male SHR. Pericyte density was negatively associated with medullary peritubular capillary (PT) congestion in both sexes following IR (male: slope = -0.04, P = 0.009; female: slope = -0.03, P = 0.0001). To further test this relationship, we used a previously reported method to reduce pericyte density in SHR. Medullary erythrocyte congestion in vasa recta (VR) and PT significantly increased following IR in both sexes when pericyte density was pharmacologically decreased (VR: P = 0.03; PT: P = 0.03). Our data support the hypothesis that pericyte density is negatively associated with the development of IR injury in SHR, which may be mediated by erythrocyte congestion in the medullary vasculature.

Interference with Gsα-Coupled Receptor Signaling in Renin-Producing Cells Leads to Renal Endothelial Damage.

Intracellular cAMP, the production of which is catalyzed by the α-subunit of the stimulatory G protein (Gsα), controls renin synthesis and release by juxtaglomerular (JG) cells of the kidney, but may also have relevance for the physiologic integrity of the kidney. To investigate this possibility, we generated mice with inducible knockout of Gsα in JG cells and monitored them for 6 months after induction at 6 weeks of age. The knockout mapped exclusively to the JG cells of the Gsα-deficient animals. Progressive albuminuria occurred in Gsα-deficient mice. Compared with controls expressing wild-type Gsα alleles, the Gsα-deficient mice had enlarged glomeruli with mesangial expansion, injury, and FSGS at study end. Ultrastructurally, the glomerular filtration barrier of the Gsα-deficient animals featured endothelial gaps, thickened basement membrane, and fibrin-like intraluminal deposits, which are classic signs of thrombotic microangiopathy. Additionally, we found endothelial damage in peritubular capillaries and vasa recta. Because deficiency of vascular endothelial growth factor (VEGF) results in thrombotic microangiopathy, we addressed the possibility that Gsα knockout may result in impaired VEGF production. We detected VEGF expression in JG cells of control mice, and cAMP agonists regulated VEGF expression in cultured renin-producing cells. Our data demonstrate that Gsα deficiency in JG cells of adult mice results in kidney injury, and suggest that JG cells are critically involved in the maintenance and protection of the renal microvascular endothelium.

Vascular Diseases of the Kidney

A number of local and systemic disease processes affect the renal vascular tree. Although the underlying mechanisms may differ, vascular diseases of the kidney all characteristically cause varying degrees of vessel obstruction, eventually leading to an impairment of renal blood flow. Acute impairment in renal function occurs in most vascular diseases of the kidney. This chapter discusses the major vascular diseases of the kidney, categorized according to the size of the affected vessel. Large-vessel diseases described are renal artery stenosis from atherosclerosis and fibromuscular dysplasia, Takayasu arteritis, and renal vein thrombosis. Medium-size-vessel diseases described are polyarteritis nodosa and Kawasaki disease. Small-vessel diseases described are those traditionally associated with glomerulopathy, including rapidly progressive glomerulonephritis and Henoch-Schönlein purpura; thrombotic microangiopathy, including thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, preeclampsia, antiphospholipid syndrome, systemic sclerosis, and malignant hypertension; sickle cell disease; and atheroembolic disease. Tables describe the American College of Rheumatology classification criteria for Takayasu arteritis and induction therapy for rapidly progressive glomerulonephritis. Figures show an overview of vascular disease of the kidney; an arteriogram of renal artery stenosis demonstrating an ostial lesion; light microscopy showing typical crescentic glomerulonephritis; purpuric eruptions in small vessel vasculitides, Henoch-Schönlein purpura, hypersensitivity vasculitis, and antineutrophil cytoplasmic autoantibody–associated disease; light microscopy showing the characteristic onion-skin lesion in scleroderma renal crisis; electron microscopy showing a glomerular capillary with thrombotic thrombocytopenic purpura; injection microradioangiograms comparing the vasa recta of a normal kidney with that in a patient with sickle cell disease; and a light microscopy that reveals an atheroembolus lodged in a small renal artery and occlusion of the vascular lumen. This chapter contains 151 references.

Vascular Diseases of the Kidney

A number of local and systemic disease processes affect the renal vascular tree. Although the underlying mechanisms may differ, vascular diseases of the kidney all characteristically cause varying degrees of vessel obstruction, eventually leading to an impairment of renal blood flow. Acute impairment in renal function occurs in most vascular diseases of the kidney. This chapter discusses the major vascular diseases of the kidney, categorized according to the size of the affected vessel. Large-vessel diseases described are renal artery stenosis from atherosclerosis and fibromuscular dysplasia, Takayasu arteritis, and renal vein thrombosis. Medium-size-vessel diseases described are polyarteritis nodosa and Kawasaki disease. Small-vessel diseases described are those traditionally associated with glomerulopathy, including rapidly progressive glomerulonephritis and Henoch-Schönlein purpura; thrombotic microangiopathy, including thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, preeclampsia, antiphospholipid syndrome, systemic sclerosis, and malignant hypertension; sickle cell disease; and atheroembolic disease. Tables describe the American College of Rheumatology classification criteria for Takayasu arteritis and induction therapy for rapidly progressive glomerulonephritis. Figures show an overview of vascular disease of the kidney; an arteriogram of renal artery stenosis demonstrating an ostial lesion; light microscopy showing typical crescentic glomerulonephritis; purpuric eruptions in small vessel vasculitides, Henoch-Schönlein purpura, hypersensitivity vasculitis, and antineutrophil cytoplasmic autoantibody–associated disease; light microscopy showing the characteristic onion-skin lesion in scleroderma renal crisis; electron microscopy showing a glomerular capillary with thrombotic thrombocytopenic purpura; injection microradioangiograms comparing the vasa recta of a normal kidney with that in a patient with sickle cell disease; and a light microscopy that reveals an atheroembolus lodged in a small renal artery and occlusion of the vascular lumen. This chapter contains 151 references.

Aquaporins in Urinary System.

Several aquaporin (AQP )-type water channels are expressed in kidney: AQP1 in the proximal tubule, thin descending limb of Henle, and vasa recta; AQP2 -6 in the collecting duct; AQP7 in the proximal tubule; AQP8 in the proximal tubule and collecting duct; and AQP11 in the endoplasmic reticulum of proximal tubule cells. AQP2 is the vasopressin-regulated water channel that is important in hereditary and acquired diseases affecting urine-concentrating ability. The roles of AQPs in renal physiology and transepithelial water transport have been determined using AQP knockout mouse models. This chapter describes renal physiologic insights revealed by phenotypic analysis of AQP knockout mice and the prospects for further basic and clinical studies.

High salt induces autocrine actions of ET-1 on inner medullary collecting duct NO production via upregulated ETBreceptor expression

The collecting duct endothelin-1 (ET-1), endothelin B (ETB) receptor, and nitric oxide synthase-1 (NOS1) pathways are critical for regulation of fluid-electrolyte balance and blood pressure control during high-salt feeding. ET-1, ETB receptor, and NOS1 are highly expressed in the inner medullary collecting duct (IMCD) and vasa recta, suggesting that there may be cross talk or paracrine signaling between the vasa recta and IMCD. The purpose of this study was to test the hypothesis that endothelial cell-derived ET-1 (paracrine) and collecting duct-derived ET-1 (autocrine) promote IMCD nitric oxide (NO) production through activation of the ETB receptor during high-salt feeding. We determined that after 7 days of a high-salt diet (HS7), there was a shift to 100% ETB expression in IMCDs, as well as a twofold increase in nitrite production (a metabolite of NO), and this increase could be prevented by acute inhibition of the ETB receptor. ETB receptor blockade or NOS1 inhibition also prevented the ET-1-dependent decrease in ion transport from primary IMCDs, as determined by transepithelial resistance. IMCD were also isolated from vascular endothelial ET-1 knockout mice (VEETKO), collecting duct ET-1 KO (CDET-1KO), and flox controls. Nitrite production by IMCD from VEETKO and flox mice was similarly increased twofold with HS7. However, IMCD NO production from CDET-1KO mice was significantly blunted with HS7 compared with flox control. Taken together, these data indicate that during high-salt feeding, the autocrine actions of ET-1 via upregulation of the ETB receptor are critical for IMCD NO production, facilitating inhibition of ion reabsorption.

Topography, Composition and Structure of Incipient Randall Plaque at the Nanoscale Level

Randall identified calcium phosphate plaques in renal papillae as the origin of kidney stones. However, little is known about the early steps of Randall plaque formation preceding the onset of urolithiasis. Our objective was to characterize the composition and the initial formation site of incipient Randall plaque in nonstone forming, living patients. Median patient age was 67.7 years. A total of 54 healthy papillae from kidneys removed for cancer and without stones were analyzed by immunohistochemistry and von Kossa staining, field emission-scanning electron microscopy with energy dispersive x-ray analysis, μ-Fourier transform infrared spectroscopy, cryo-transmission electron microscopy coupled to selected area electron diffraction and electron energy loss spectroscopy. Incipient Randall plaque was observed in 72.7% of kidneys. As expected, carbonated apatite was the main component of microcalcifications but amorphous calcium phosphate and whitlockite were identified in 80% and 40% of papillae, respectively. Incipient plaques were noted in the deepest part of the papillae around the loop of Henle tip as well as around the vasa recta, representing 62.4% and 37.2% of microcalcifications, respectively. Plaques were rarely close to collecting ducts. At the nanoscale level incipient calcifications were often composed of several nanocrystals in organic material that looked like microvesicles. Incipient Randall plaque is frequent. It appears not only at the extreme tip of the renal papillae around the hairpin structure of the loop of Henle but also around the vasa recta. Nanoscale analyses suggest a local nucleation process promoting nanocrystal growth in a supersaturated milieu. In addition, plaques contain various calcium and magnesium phosphates, and not only carbonated apatite.

Safety and Risk of Superselective Transcatheter Arterial Embolization for Acute Lower Gastrointestinal Hemorrhage with N-Butyl Cyanoacrylate: Angiographic and Colonoscopic Evaluation

PurposeTo retrospectively evaluate the safety and risk of transcatheter arterial embolization (TAE) with N-butyl cyanoacrylate (NBCA) for urgent acute arterial bleeding control in the lower gastrointestinal tract by angiography and colonoscopy. Materials and MethodsNBCA TAE was performed in 16 patients (mean age, 63.7 y) with lower gastrointestinal bleeding (diverticular hemorrhage, tumor bleeding, and intestinal tuberculosis). Angiographic evaluation was performed by counting the vasa recta filled with casts of NBCA and ethiodized oil (Lipiodol) after TAE. Patients were classified as follows: group Ia, with a single vas rectum with embolization of 1 branch (n = 6); group Ib, with a single vas rectum with embolization of ≥ 2 branches (n = 8); group II, with embolization of multiple vasa recta (n = 2). All patients underwent colonoscopy within 1 month, and ischemic complications (ulcer, scar, mucosal swelling, fibrinopurulent debris, and necrosis) were evaluated. ResultsThe procedure was successful in all patients. No ischemic change was observed in any patients in group Ia and in two patients in group Ib. Ischemic changes were observed in six group Ib patients and both group II patients. Group Ib patients experienced ischemic complications that improved without treatment. One patient in group II underwent resection for intestinal perforation after embolization of three vasa recta. One patient in group II with sigmoid stricture with embolization of six vasa recta required prolonged hospitalization. ConclusionsNBCA embolization of ≥ 3 vasa recta can induce ischemic bowel damage requiring treatment. NBCA TAE of one vas rectum with ≥ 2 branches could also induce ischemic complications. However, these were silent and self-limited.

CT enterography in the evaluation of Crohn's disease

PropositionCrohn's disease (CD) is a chronic inflammatory process that affects various parts of the gastrointestinal tract, from the mouth to the anus with unknown etiology and variable clinical presentation. CD diagnosis is based on clinical and complementary tests. Among the complementary tests, enterography with CT enterography has shown good results in the evaluation of this disease. MethodsThe patients evaluated were submitted to a questionnaire on the clinical manifestations of the disease and an CT enterography was obtained. The studies were reviewed by an experienced radiologist looking for radiological signs of CD. ResultsThe mean age was 40 years, with a predominance of women. The main clinical manifestations are diarrhea in 24 (70%), hematochezia in 19 (55%), abdominal pain in 29 (85%) and weight loss in 22 (64%) patients. The main findings on CT enterography were an intestinal wall enhancement signal in 23 patients (67%), vascular engorgement (vasa recta) in 20 (58%), parenteral fat densification in 14 (41%), intestinal wall thickening in 22 (64%), and lymph node enlargement in 17 (50%) of patients. ConclusionThis study showed that CT enterography presents a good assessment of intestinal involvement by CD.