Urinary Space

2020 ◽  
Author(s):  
Keyword(s):  
1996 ◽  
Vol 271 (2) ◽  
pp. F261-F268 ◽  
Author(s):  
M. Bendayan ◽  
I. Londono

The proximal tubule epithelial handling of native and glycated albumin was evaluated by quantitative immunocytochemistry. Native bovine serum albumin (BSA) and its glycated form (gBSA), tagged to different haptens, were simultaneously injected in anesthetized mice and maintained in circulation for 10 or 60 min. Both albumins were localized within the capillary lumen, in glomerular and peritubular basement membranes, the urinary space, and cellular compartments of the proximal tubular epithelial cells. In these cells, both forms of albumin were concomitantly found within the same endocytic-lysosomal system. Morphometric evaluations have indicated higher proportions of gBSA in the urinary space, reflecting probably a significant glomerular filtration of this form of albumin combined to a lesser reabsorptive clearance. Indeed, higher proportions of native BSA were found in the endocytic compartment of the tubular epithelial cells, suggesting its preferential reabsorption. The present study thus supports a preferential glomerular filtration of gBSA with a facilitated filtration of native BSA in the presence of the glycated one. It also demonstrates the tubular reabsorption of BSA and gBSA through a common endocytic pathway, in which the native BSA is preferentially reabsorbed with respect to its glycated form.


2019 ◽  
Vol 20 (9) ◽  
pp. 2205 ◽  
Author(s):  
Juan Antonio Moreno ◽  
Ángel Sevillano ◽  
Eduardo Gutiérrez ◽  
Melania Guerrero-Hue ◽  
Cristina Vázquez-Carballo ◽  
...  

Glomerular hematuria is a cardinal symptom of renal disease. Glomerular hematuria may be classified as microhematuria or macrohematuria according to the number of red blood cells in urine. Recent evidence suggests a pathological role of persistent glomerular microhematuria in the progression of renal disease. Moreover, gross hematuria, or macrohematuria, promotes acute kidney injury (AKI), with subsequent impairment of renal function in a high proportion of patients. In this pathological context, hemoglobin, heme, or iron released from red blood cells in the urinary space may cause direct tubular cell injury, oxidative stress, pro-inflammatory cytokine production, and further monocyte/macrophage recruitment. The aim of this manuscript is to review the role of glomerular hematuria in kidney injury, the role of inflammation as cause and consequence of glomerular hematuria, and to discuss novel therapies to combat hematuria.


2011 ◽  
Vol 21 (3) ◽  
pp. 151
Author(s):  
Terry M Mayhew

The renal corpuscle is a multi-compartment unit of kidney morphology which is important for normal ultrafiltration of blood. Its structure is perturbed during ontogeny, disease and experimental manipulation. Transmission electron microscopy and second-order stereological tools (cross covariance and cross correlation functions) were used to examine 3-D spatial interactions between the main tissue compartments (glomerular capillaries, podocytes, mesangium, urinary space) of the renal corpuscle in normal adult rats. Volume densities, covariance and correlation functions were estimated by counting test points (randomly positioned) and linear dipole probes (randomly positioned and orientated) superimposed on random samples of photomontages prepared from ultrathin resin sections. Differences in clustering exist between compartments (at distances < 8 μm, mesangium is the most tightly-clustered and capillaries the least tightly-clustered compartment; > 8 μm, compartments are neither hypodisperse nor hyperdisperse). Despite this, cross correlation functions for linked sets of compartments (capillary-mesangium, capillary-podocytes, capillary-urinary space, mesangium-podocytes, mesangium-urinary space and podocytes-urinary space) did not vary with dipole distance. This indicates that the spatial relations between linked compartments do not favour attraction or repulsion. In addition, inter-individual variation is greater for some linked compartments than others. Variation is less for compartments (capillary-podocyte and capillary-urinary space) which contribute to the ultrafiltration barrier and this probably reflects the structural and functional integration evident at this site as well as the higher volume densities (and smaller inter-subject variation) for capillaries.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Megumi Kondo ◽  
KENGO KIDOKORO ◽  
Yoshihisa Wada ◽  
Atsuyuki Tokuyama ◽  
Hiroyuki Kadoya ◽  
...  

Abstract Background and Aims In most developed countries, diabetic kidney disease (DKD) is the most common cause of chronic kidney disease, which can lead to end-stage renal disease. In recent clinical trials, sodium–glucose cotransporter 2 inhibitors (SGLT2is) slowed the progression of kidney disease as compared with a placebo in patients with type 2 diabetes. One of the main mechanisms of the renoprotective effects of SCLT2is in DKD is considered the ability of these inhibitors to improve glomerular hyperfiltration. We previously demonstrated that the adenosine/adenosine A1 receptor pathway played a pivotal role in the tubuloglomerular feedback(TGF) system in a type 1 diabetic model, Akita mice (Circulation, 2019). We also reported that increased oxidative stress was involved in the pathogenesis of diabetic vascular complications. Uncoupling of endothelial nitric oxide (NO) synthase (eNOS) via oxidation of tetrahydrobiopterin (BH4), a cofactor required for NO production, played a major role in generation of oxidative stress (AJPRP, 2005; JASN, 2013). In the present study, we explored the renal protective effects of SGLT2 inhibition, with a focus on glomerular hemodynamics and glomerular oxidative stress. Method This study used type 2 diabetic db/db mice and db/m+ mice as a control (male, 8wk old). We developed a novel method to measure the glomerular filtration rate of single nephrons (SNGFRs) in mice using multiphoton laser microscopy. In the first experiment, we measured the SNGFRs in 12 wk-old db/db and db/m+ mice to confirm glomerular hyperfiltration. Next, we evaluated the SNGFRs change before and after the administration of a single dose of canagliflozin (CANA) (10 mg/kg). The SNGFRs, glomerular permeability of macromolecules, glomerular reactive oxygen species (ROS) and NO production, and tetrahydrobiopterin (BH4) level in serum and kidney were evaluated after the CANA treatment for 8 wk. Finally, human glomerular endothelial cells (hGECs) were exposed to normal glucose (5 mmol/L), high glucose (30 mmol/L of D-glucose), or a hyperosmotic control (5 mmol/L of D-glucose plus 25 mmol/L of L-glucose) in the presence or absence of CANA (10 μmol/L). Results The CANA treatment ameliorated glomerular hyperfiltration in the db/db mice. In the db/db mice, glomerulus ROS production increased, and NO production decreased as compared with the levels in the control mice. CANA improved the imbalance between ROS and NO production. The serum and kidney concentrations of BH4 declined in the non-treated db/db mice, whereas the CANA treatment preserved the BH4 level. Leakage of 70-kD FITC-labeled albumin into the urinary space was observed in the db/db mice. The CANA treatment reduced the amount of FITC-labeled albumin in the urinary space of the db/db mice. The CANA treatment also alleviated vascular endothelial damage in glomeruli. BH4 levels decreased in the hGECs exposed to high glucose. CANA did not improved BH4 level in the hGECs exposed to high glucose. Conclusion SGLT2i ameliorated glomerular hyperfiltration, preserving BH4 levels and improving the glomerular ROS/NO imbalance in type 2 diabetic mice.


1974 ◽  
Vol 139 (5) ◽  
pp. 1283-1302 ◽  
Author(s):  
E. E. Schneeberger ◽  
P. D. Leber ◽  
M. J. Karnovsky ◽  
R. T. McCluskey

The altered functional properties of the glomerular capillary wall in a model of autologous immune complex disease (Heymann's nephritis) was studied by electron microscopy using intravenously injected protein tracers of varying molecular weight. There was an increase in the permeability of the glomerular basement membrane (GBM) itself to large molecules; this change was focal and was found in those areas where the GBM contained immune complex deposits. Both ferritin and catalase, tracers normally restricted from passing the glomerular filter, were present in the urinary space within minutes of injection. No evidence was obtained for increased glomerular epithelial transport in this disease. Foot process swelling and "close" junction formation was moderate, even in animals with marked degrees of proteinuria. Indirect evidence, therefore, makes an alteration in the slit pore complex likely. In addition, there was immediate and selective concentration of all tracers within deposits, though ferritin was partially excluded from some deposits. This phenomenon may be of significance in the perpetuation of the disease.


Author(s):  
Sarah Hunt ◽  
Yoav Segal ◽  
Kevin D. Dorfman ◽  
Victor H. Barocas

Transport in the kidney is critically important in normal function and in disease. Solute transport occurs in many locations within the kidney, including convection within the capillaries, filtration across the basement membrane, and convection/diffusion within the mesangium (Figure 1). Models of transport in the kidney have traditionally focused on ultrafiltration [1], which is the predominant pathway for fluid and solutes passing into the urinary space. However, the mesangium is often the site of the first symptoms in disease [2], suggesting that mesangial transport is significant, at least in some cases.


1978 ◽  
Vol 234 (6) ◽  
pp. F455-F460 ◽  
Author(s):  
B. M. Brenner ◽  
T. H. Hostetter ◽  
H. D. Humes

The formation of glomerular ultrafiltrate is dependent on the interplay of glomerular pressures and flows as well as the intrinsic permselectivity properties of the glomerular capillary wall. These intrinsic permeability properties serve to exclude macromolecules from the urinary space, based on size as well as net molecular charge discrimination. Neutral dextrans with molecular radii less than 20 A cross the glomerular wall without measurable restriction, whereas dextrans with radii greater than 42 A are almost completely barred. For any given size, negatively charged macromolecules are restricted to a greater extent than neutral molecules. Additionally, positively charged molecules are enhanced in their ability to cross the glomerular wall compared to similarly sized neutral polymers. The concept of a charge barrier, due to fixed negative charges within the glomerular wall, is also supported by morphological studies. Glomerular injury, leading to proteinuria, has been associated with loss of the charge-selective properties of these capillaries. Loss of glomerular fixed negative charges may also result in the foot process fusion and mesangial cell dysfunction often observed in proteinuric states.


2020 ◽  
Vol 318 (5) ◽  
pp. F1246-F1251
Author(s):  
Christoph Wrede ◽  
Jan Hegermann ◽  
Christian Mühlfeld

Podocytes are highly specialized cells with a clear cell polarity. It is known that in health and disease, microvilli protrude from the apical surface of the podocytes into the urinary space. As a basis to better understand the podocyte microprojections/microvilli, the present study analyzed their spatial localization, extension, and contact site with parietal epithelial cells (PECs). Using different electron microscopic (EM) techniques, we analyzed renal corpuscles of healthy young adult male C57BL/6 mice fixed by vascular perfusion. Serial block-face scanning EM was used to visualize entire corpuscles, focused ion beam scanning EM was performed to characterize microprojection/microvilli-rich regions at higher magnification, and transmission EM of serial sections was used to analyze the contact zone between podocyte microprojections and PECs. Numerous microprojections originating from the primary processes of podocytes were present in the urinary space in all regions of the corpuscle. They often reached the apical surface of the PEC but did not make junctional contacts. At high resolution, it was observed that the glycocalyx of both cells was in contact. Depending on the distance between podocytes and PECs, these microprojections had a stretched or coiled state. The present study shows that microprojections/microvilli of podocytes are a physiological feature of healthy mouse kidneys and are frequently in contact with the apical surface of PECs, thus spanning the urinary space. It is proposed that podocyte microprojections serve mechanosensory or communicative functions between podocytes and PECs.


PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e75547 ◽  
Author(s):  
Ana Tobar ◽  
Yaacov Ori ◽  
Sydney Benchetrit ◽  
Gai Milo ◽  
Michal Herman-Edelstein ◽  
...  

2009 ◽  
Vol 297 (6) ◽  
pp. F1477-F1501 ◽  
Author(s):  
Puneet Khandelwal ◽  
Soman N. Abraham ◽  
Gerard Apodaca

The uroepithelium sits at the interface between the urinary space and underlying tissues, where it forms a high-resistance barrier to ion, solute, and water flux, as well as pathogens. However, the uroepithelium is not simply a passive barrier; it can modulate the composition of the urine, and it functions as an integral part of a sensory web in which it receives, amplifies, and transmits information about its external milieu to the underlying nervous and muscular systems. This review examines our understanding of uroepithelial regeneration and how specializations of the outermost umbrella cell layer, including tight junctions, surface uroplakins, and dynamic apical membrane exocytosis/endocytosis, contribute to barrier function and how they are co-opted by uropathogenic bacteria to infect the uroepithelium. Furthermore, we discuss the presence and possible functions of aquaporins, urea transporters, and multiple ion channels in the uroepithelium. Finally, we describe potential mechanisms by which the uroepithelium can transmit information about the urinary space to the other tissues in the bladder proper.


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