Correlation of Glomerular Size With Donor-recipient Factors and With Response to Injury

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Joseph P. Grande ◽  
Erika S. Helgeson ◽  
Arthur J. Matas
Keyword(s):  
Glomerular Size

Angiotensin II regulates nephrogenesis and renal vascular development

1995 ◽  
Vol 269 (1) ◽  
pp. F110-F115 ◽  
Author(s):  
A. Tufro-McReddie ◽  
L. M. Romano ◽  
J. M. Harris ◽  
L. Ferder ◽  
R. A. Gomez
Keyword(s):  
Angiotensin Ii ◽  
Kidney Development ◽  
Rana Catesbeiana ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Ang Ii ◽  
Newborn Rats ◽  
Sprague Dawley ◽  
Renal Growth ◽  
Glomerular Size ◽  
Renal Vascular

To test the hypothesis that angiotensin II (ANG II) is necessary for normal embryonic and postnatal kidney development, the effect of angiotensin receptor blockade or angiotensin converting enzyme inhibition on nephrovascular development was studied in newborn Sprague-Dawley rats and in Rana catesbeiana tadpoles undergoing prometamorphosis. Blockade of ANG II type 1 receptor (AT1) in newborn rats induced an arrest in nephrovascular maturation and renal growth, resulting in altered kidney architecture, characterized by fewer, thicker, and shorter afferent arterioles, reduced glomerular size and number, and tubular dilatation. Inhibition of ANG II generation in tadpoles induced even more marked developmental renal abnormalities. Blockade of ANG II type 2 receptor (AT2) in newborn rats did not alter renal growth or morphology. Results indicate that ANG II regulates nephrovascular development, a role that is conserved across species.

Overexpression of angiotensin type 2 receptor ameliorates glomerular injury in a mouse remnant kidney model

2004 ◽  
Vol 286 (3) ◽  
pp. F516-F525 ◽  
Author(s):  
Naoko Hashimoto ◽  
Yohei Maeshima ◽  
Minoru Satoh ◽  
Masahiro Odawara ◽  
Hitoshi Sugiyama ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β ◽  
Glomerular Injury ◽  
Wild Mice ◽  
Angiotensin Type 2 Receptor ◽  
Glomerular Size ◽  
Nitric Oxide Metabolites

Angiotensin II mediates the progression of renal disease through the type 1 receptor (AT1R). Recent studies have suggested that type 2 receptor (AT2R)-mediated signaling inhibits cell proliferation by counteracting the actions of AT1R. The aim of the present study was to determine the effect of AT2R overexpression on glomerular injury induced by ⅚ nephrectomy (⅚Nx). AT2R transgenic mice (AT2-Tg), overexpressing AT2R under the control of α-smooth muscle actin (α-SMA) promoter, and control wild-type mice (Wild) were subjected to ⅚Nx. In AT2-Tg mice, the glomerular expression of AT2R was upregulated after ⅚Nx. Urinary albumin excretion at 12 wk after ⅚Nx was decreased by 33.7% in AT2-Tg compared with Wild mice. Glomerular size in AT2-Tg mice was significantly smaller than in Wild mice after ⅚Nx (93.1 ± 3.0 vs. 103.3 ± 1.8 μm; P < 0.05). Immunohistochemistry revealed significant decreases in glomerular expression of platelet-derived growth factor-BB chain (PDGF-BB) and transforming growth factor-β1 (TGF-β1) in AT2-Tg with ⅚Nx compared with Wild mice. Urinary excretion of nitric oxide metabolites was increased 2.5-fold in AT2-Tg compared with Wild mice. EMSA showed that activation of early growth response gene-1, which induces the transcription of PDGF-BB and TGF-β1, was decreased in AT2-Tg mice. These changes in AT2-Tg mice at 12 wk after ⅚Nx were blocked by the AT2R antagonist PD-123319. Taken together, our findings suggest that AT2R-mediated signaling may protect from glomerular injuries induced by ⅚Nx and that overexpression of AT2R may serve as a potential therapeutic strategy for glomerular disorders.

Filtration by superficial and deep glomeruli of normovolemic and volume-depleted rats

1986 ◽  
Vol 250 (1) ◽  
pp. F86-F91
Author(s):  
R. V. Pinnick ◽  
V. J. Savin
Keyword(s):  
Basement Membrane ◽  
Maximum Rate ◽  
Rate Of Change ◽  
The Other ◽  
Membrane Area ◽  
Morphometric Analyses ◽  
Three Samples ◽  
Glomerular Size ◽  
Glomerular Ultrafiltration

We measured glomerular ultrafiltration coefficient (Kf) of isolated superficial (S) and deep (D) glomeruli of normovolemic and volume-depleted rats. Filtration was induced in vitro, and Kf was calculated from the maximum rate of change in glomerular size. Basement membrane area (A) for each glomerulus was estimated from morphometric analyses, and glomerular capillary hydraulic conductivity (Lp) was calculated by the formula Lp = Kf/A. Kf of S and D glomeruli of normovolemic rats were 2.98 +/- 0.98 and 4.25 +/- 0.07 nl . min-1 . mmHg-1, respectively. In hypovolemic rats, Kf of S glomeruli fell by approximately 50% to 1.52 +/- 0.14 nl . min-1 . mmHg-1 (P less than 0.001), whereas Kf of D glomeruli remained unchanged at 4.28 +/- 0.10 nl . min-1 . mmHg-1. Lp, calculated using the peripheral capillary area, averaged 1.98 +/- 0.09 and 1.98 +/- 0.06 microliter . min-1 . mmHg-1 . cm-2 in S and D glomeruli of normovolemic rats and 1.89 +/- 0.11 microliter . min-1 . mmHg-1 . cm-2 in D glomeruli of hypovolemic rats. Lp of S glomeruli of volume-depleted rats (0.90 +/- 0.03 microliter . min-1 . mmHg-1 . cm-2) was lower than in any of the other three samples. Mild hypovolemia causes the Kf of S glomeruli to decline, whereas Kf of D glomeruli remains constant. The decrease in Kf occurs without an alteration in capillary area and is most likely due to a decrease in Lp.

Capillary network structure does not affect theoretical analysis of glomerular size selectivity

1995 ◽  
Vol 268 (5) ◽  
pp. F972-F979
Author(s):  
A. Remuzzi ◽  
B. Ene-Iordache
Keyword(s):  
Pressure Drop ◽  
Homogeneous Model ◽  
Wistar Rat ◽  
Size Selectivity ◽  
Membrane Pore ◽  
Heterogeneous Model ◽  
Glomerular Size ◽  
The Difference ◽  
Membrane Pore Size ◽  
Log Normal

Anatomical studies have demonstrated that the glomerular capillaries are complex and heterogeneous networks. Conventional models of glomerular size selectivity, however, are based on the assumption of simplified geometries. We developed a theoretical model of glomerular size-selective function based on the geometric data obtained in a previous reconstruction of a glomerular network from a normal Munich-Wistar rat. This heterogeneous model was compared with the homogeneous model conventionally used to calculate membrane selective parameters from the fractional clearance of two test solutes, neutral dextran and Ficoll. For both models we assumed a hypothetical log-normal distribution of pore sizes and calculated optimal membrane pore-size parameters using previously published values of fractional clearances. The difference between the sieving coefficients calculated with the two models was negligible, never exceeding 5.5%. Since the homogeneous model does not consider the pressure drop along the glomerular capillary, we also computed fractional clearances with the homogeneous model, assuming the same pressure drop as in the heterogeneous one. The differences in computed fractional clearances using the homogeneous model with and without a pressure drop were less than 1.2%. We concluded that models based on identical capillary networks can therefore be used for interpreting sieving coefficients for macromolecules.

scholarly journals Increased Urine IgM and IgG2Levels, Indicating Decreased Glomerular Size Selectivity, Are Not Affected by Dalteparin Therapy in Patients with Type 2 Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ole Torffvit ◽  
Majid Kalani ◽  
Jan Apelqvist ◽  
Björn Eliasson ◽  
Jan W. Eriksson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Physiological Saline ◽  
Diabetic Patients ◽  
Size Selectivity ◽  
Type 2 Diabetic Patients ◽  
Once Daily ◽  
Urinary Levels ◽  
Glomerular Size ◽  
Type 2 Diabetic

Fifty-four type 2 diabetic patients with neuroischemic foot ulcers were randomised to treatment with 5000 IU of dalteparin, (n=28), or physiological saline, (n=26), once daily until ulcer healing or for a maximum of 6 months. Thirty-three patients had normo-, 15 micro-, and 6 macroalbuminuria. The urinary levels of IgM and IgG2were elevated in 47 and 50 patients, respectively. Elevated urinary levels of IgM and IgG2indicate decreased glomerular size selectivity. Urine IgM levels were associated with IGF-1/IGFBP-1 and IGFBP-1 levels. Dalteparin treatment increased urinary levels of glycosaminoglycans (P<0.001) and serum IGFBP-1 (P<0.05) while no significant effects were seen in any of the other studied parameters. In conclusion, dalteparin therapy in patients with type 2 diabetes had no effects on urinary levels of albumin, IgM, or IgG2despite significantly increased glycosaminoglycans in urine. Elevated urinary levels of IgM and IgG2might be more sensitive markers of renal disease than albuminuria in patients with type 2 diabetes and antihypertensive therapy.

ACE inhibition and ANG II receptor blockade improve glomerular size-selectivity in IgA nephropathy

1999 ◽  
Vol 276 (3) ◽  
pp. F457-F466 ◽  
Author(s):  
Andrea Remuzzi ◽  
Norberto Perico ◽  
Fabio Sangalli ◽  
Giovanni Vendramin ◽  
Monica Moriggi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Iga Nephropathy ◽  
Ace Inhibitors ◽  
Ace Inhibition ◽  
Maximum Effect ◽  
Double Blind Study ◽  
Ang Ii ◽  
Size Selectivity ◽  
Double Blind ◽  
Glomerular Size

Protein trafficking across the glomerular capillary has a pathogenic role in subsequent renal damage. Despite evidence that angiotensin-converting enzyme (ACE) inhibitors improve glomerular size-selectivity, whether this effect is solely due to ANG II blocking or if other mediators also play a contributory role is not clear yet. We studied 20 proteinuric patients with IgA nephropathy, who received either enalapril (20 mg/day) or the ANG II receptor blocker irbesartan (100 mg/day) for 28 days in a randomized double-blind study. Measurements of blood pressure, renal hemodynamics, and fractional clearance of neutral dextran of graded sizes were performed before and after 28 days of treatment. Both enalapril and irbesartan significantly reduced blood pressure over baseline. This reduction reached the maximum effect 4–6 h after drug administration but did not last for the entire 24-h period. Despite transient antihypertensive effect, proteinuria was effectively reduced by both treatments to comparable extents. Neither enalapril nor irbesartan modified the sieving coefficients of small dextran molecules, but both effectively reduced transglomerular passage of large test macromolecules. Theoretical analysis of sieving coefficients showed that neither drug affected significantly the mean pore radius or the spread of the pore-size distribution, but both importantly and comparably reduced the importance of a nonselective shunt pathway. These data suggest that antagonism of ANG II is the key mechanism by which ACE inhibitors exert their beneficial effect on glomerular size-selective function and consequently on glomerular filtration and urinary output of plasma proteins.

scholarly journals Early podocyte injury and elevated levels of urinary podocyte-derived extracellular vesicles in swine with metabolic syndrome: role of podocyte mitochondria

2019 ◽  
Vol 317 (1) ◽  
pp. F12-F22 ◽  
Author(s):  
Li-Hong Zhang ◽  
Xiang-Yang Zhu ◽  
Alfonso Eirin ◽  
Arash Aghajani Nargesi ◽  
John R. Woollard ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Extracellular Vesicles ◽  
Light And Electron Microscopy ◽  
Urinary Concentration ◽  
Glomerular Injury ◽  
Podocyte Injury ◽  
Early Markers ◽  
Nutrient Surplus ◽  
Glomerular Size ◽  
Foot Process

Metabolic syndrome (MetS) is associated with nutrient surplus and kidney hyperfiltration, accelerating chronic renal failure. The potential involvement of podocyte damage in early MetS remains unclear. Mitochondrial dysfunction is an important determinant of renal damage, but whether it contributes to MetS-related podocyte injury remains unknown. Domestic pigs were studied after 16 wk of diet-induced MetS, MetS treated with the mitochondria-targeted peptide elamipretide (ELAM; 0.1 mg·kg−1·day−1 sc) for the last month of diet, and lean controls ( n = 6 pigs/group). Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured using multidetector computed tomography, and podocyte and mitochondrial injury were measured by light and electron microscopy. Urinary levels of podocyte-derived extracellular vesicles (pEVs; nephrin positive/podocalyxin positive) were characterized by flow cytometry. Body weight, blood pressure, RBF, and GFR were elevated in MetS. Glomerular size and glomerular injury score were also elevated in MetS and decreased after ELAM treatment. Evidence of podocyte injury, impaired podocyte mitochondria, and foot process width were all increased in MetS but restored with ELAM. The urinary concentration of pEVs was elevated in MetS pigs and directly correlated with renal dysfunction, glomerular injury, and fibrosis and inversely correlated with glomerular nephrin expression. Additionally, pEV numbers were elevated in the urine of obese compared with lean human patients. Early MetS induces podocyte injury and mitochondrial damage, which can be blunted by mitoprotection. Urinary pEVs reflecting podocyte injury might represent early markers of MetS-related kidney disease and a novel therapeutic target.

scholarly journals Analysis of the three dimensional structure of the kidney glomerulus capillary network

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mark Terasaki ◽  
Jason Cory Brunson ◽  
Justin Sardi
Keyword(s):  
3D Structure ◽  
Three Dimensional ◽  
The Body ◽  
Capillary Network ◽  
Dimensional Structure ◽  
Pixel Resolution ◽  
Longitudinal Splitting ◽  
Kidney Glomerulus ◽  
Minimum Number ◽  
Glomerular Size

AbstractThe capillary network of the kidney glomerulus filters small molecules from the blood. The glomerular 3D structure should help to understand its function, but it is poorly characterized. We therefore devised a new approach in which an automated tape collecting microtome (ATUM) was used to collect 0.5 μm thick serial sections from fixed mouse kidneys. The sections were imaged by scanning electron microscopy at ~ 50 nm/pixel resolution. With this approach, 12 glomeruli were reconstructed at an x–y–z resolution ~ 10 × higher than that of paraffin sections. We found a previously undescribed no-cross zone between afferent and efferent branches on the vascular pole side; connections here would allow blood to exit without being adequately filtered. The capillary diameters throughout the glomerulus appeared to correspond with the amount of blood flow within them. The shortest path (minimum number of branches to travel from afferent to efferent arterioles) is relatively independent of glomerular size and is present primarily on the vascular pole size. This suggests that new branches and longer paths form on the urinary pole side. Network analysis indicates that the glomerular network does not form by repetitive longitudinal splitting of capillaries. Thus the 3D structure of the glomerular capillary network provides useful information with which to understand glomerular function. Other tissue structures in the body may benefit from this new three dimensional approach.

Sign in / Sign up

Export Citation Format

Share Document