scholarly journals Glomerular Damage in Experimental Proliferative Glomerulonephritis Under Glomerular Capillary Hypertension

2015 ◽  
Vol 40 (2) ◽  
pp. 188-199 ◽  
Author(s):  
Pei-Rong Wang ◽  
Hiroshi Kitamura ◽  
Akira Shimizu ◽  
Nobuaki Yamanaka
Keyword(s):  
Proliferative Glomerulonephritis ◽  
Glomerular Capillary ◽  
Glomerular Capillary Hypertension ◽  
Glomerular Damage

scholarly journals Live Imaging of Monocyte Subsets in Immune Complex-Mediated Glomerulonephritis Reveals Distinct Phenotypes and Effector Functions

2020 ◽  
Vol 31 (11) ◽  
pp. 2523-2542
Author(s):  
Tabitha Turner-Stokes ◽  
Ana Garcia Diaz ◽  
Damilola Pinheiro ◽  
Maria Prendecki ◽  
Stephen P. McAdoo ◽  
...  
Keyword(s):  
Immune Complex ◽  
Immune Complexes ◽  
Monocyte Subset ◽  
Lymphocyte Function ◽  
Monocyte Subsets ◽  
Effector Functions ◽  
Glomerular Capillary ◽  
Glomerular Endothelium ◽  
Classical Monocytes ◽  
Glomerular Damage

BackgroundImmune complexes within glomerular capillary walls cause crescentic GN (CrGN). Monocytes and macrophages are important in mediating CrGN, but little work has been done to phenotype the subpopulations involved and determine their respective contributions to glomerular inflammation.MethodsLive glomerular imaging using confocal microscopy monitored intravascular monocyte subset behavior during nephrotoxic nephritis (NTN) in a novel WKY-hCD68-GFP monocyte/macrophage reporter rat strain. Flow cytometry and qPCR further analyzed ex vivo the glomerular leukocyte infiltrate during NTN.ResultsNon-classical monocytes surveyed the glomerular endothelium via lymphocyte function-associated antigen 1 (LFA-1) in the steady state. During NTN, non-classical monocytes were recruited first, but subsequent recruitment and retention of classical monocytes was associated with glomerular damage. Monocytes recruited to the glomerular vasculature did not undergo transendothelial migration. This finding suggests that inflammation in immune complex-mediated CrGN is predominantly intravascular, driven by dynamic interactions between intravascular blood monocytes and the endothelium. Glomerular endothelium and non-classical monocytes overexpressed a distinct chemokine axis, which may orchestrate inflammatory myeloid cell recruitment and expression of damage mediators. Reduced classical monocyte recruitment in Lewis rats during NTN confirmed a role for CD16 in mediating glomerular damage.ConclusionsMonocyte subsets with distinct phenotypes and effector functions may be important in driving inflammation in experimental CrGN resulting from immune complexes formed within the glomerular capillary wall. LFA-1–dependent endothelial surveillance by non-classical monocytes may detect immune complexes through CD16, orchestrating the inflammatory response through intravascular retention of classical monocytes, which results in glomerular damage and proteinuria.

Glomerular and tubular damage in normotensive and hypertensive rats

2005 ◽  
Vol 288 (4) ◽  
pp. F665-F672 ◽  
Author(s):  
Jarle Ofstad ◽  
Bjarne M. Iversen
Keyword(s):  
Interstitial Fibrosis ◽  
Cell Damage ◽  
Pressure Variation ◽  
Renal Diseases ◽  
Common Mechanism ◽  
Tubular Damage ◽  
Hypertensive Rats ◽  
Glomerular Capillary ◽  
Tubular Diameter ◽  
Glomerular Damage

Tubular cell damage is an important mediator of interstitial fibrosis in chronic renal diseases. Glomerular and tubular damage in genetic hypertension was therefore studied. Tubular and glomerular damage was investigated in 10-, 40-, and 70-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and compared with glomerular capillary pressure (PGC) and glomerulosclerosis in superficial (OC) and juxtamedullary (JMC). Tubular vimentin was used as criterion of tubular damage. Variation in tubular diameter was measured during change in perfusion pressure, and ureter ligation was used to demonstrate the relationship between tubular pressure and appearance of vimentin-positive cells. Tubular and glomerular damage was most pronounced in JMC and greater in SHR than in WKY. It was absent in 10-wk-old WKY and significantly higher in JMC of SHR compared with WKY at 70 wk of age. Numbers of vimentin-positive segments were 18 ± 9 vs. 38 ± 7% in JMC of 70-wk-old WKY and SHR ( P < 0.02), and glomerulosclerosis was seen in 8 ± 3 vs. 19 ± 5% of glomeruli in JMC of 70-wk-old WKY and SHR, respectively ( P < 0.01). PGCwas 45 ± 3 mmHg in JMC of WKY and 57 ± 3 mmHg in JMC of 70-wk-old SHR ( P < 0.001). Tubular diameter variation was greatest in SHR ( P < 0.05) during pressure variation. Proteinuria was present only in 40- and 70-wk-old SHR and did not correlate with tissue damage. Tubular and glomerular damage in both strains develops in parallel and may be caused by a common mechanism, which may be glomerular capillary and tubular wall stretch during acute blood pressure variation which is greatest in JMC in SHR.

scholarly journals A Case of Proliferative Glomerulonephritis with Monoclonal IgG Deposits That Showed Predominantly Membranous Features

2017 ◽  
Vol 2017 ◽  
pp. 1-5
Author(s):  
Homare Shimohata ◽  
Kentaro Ohgi ◽  
Hiroshi Maruyama ◽  
Yasunori Miyamoto ◽  
Mamiko Takayashu ◽  
...  
Keyword(s):  
Light Microscopy ◽  
Proliferative Glomerulonephritis ◽  
Light Chains ◽  
The Novel ◽  
Immunofluorescence Study ◽  
Pathological Findings ◽  
Mesangial Proliferation ◽  
Glomerular Capillary ◽  
Almost All ◽  
Capillary Walls

In 2004, the novel category of monoclonal IgG deposition disease has been proposed and termed “proliferative glomerulonephritis with monoclonal IgG deposits” (PGNMID). This disease is characterized by membranoproliferative glomerulonephritis and staining for a single light-chain isotype and gamma heavy-chain subclass. A 76-year-old male who had monoclonal gammopathy was referred to our hospital because of proteinuria. The renal biopsy showed diffuse thickening of the glomerular capillary walls with focal mesangial proliferation. On immunofluorescence study, only IgG1 among the four subclasses and lambda light chains were detected mainly in the glomerular capillary walls. From these results, we diagnosed our case as PGNMID showing predominantly membranous features. Almost all pathological findings on light microscopy of PGNMID are membranoproliferative GN or endocapillary proliferative GN, while membranous GN cases are rare. Here, we present the case of PGNMID that showed predominantly membranous features on light microscopy.

scholarly journals Anemia ameliorates progressive renal injury in experimental DOCA-salt hypertension.

1991 ◽  
Vol 1 (10) ◽  
pp. 1180-1185
Author(s):  
H M Lafferty ◽  
D L Garcia ◽  
H G Rennke ◽  
J L Troy ◽  
S Anderson ◽  
...  
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Glomerular Sclerosis ◽  
Glomerular Injury ◽  
Glomerular Capillary ◽  
Human Erythropoietin ◽  
Glomerular Hypertension ◽  
Salt Hypertension ◽  
Contrast Reduction ◽  
Glomerular Capillary Hypertension

To explore the role of systemic hematocrit in the vascular adaptations which characterize desoxycorticosterone-salt hypertension, studies were performed in three groups of rats with uninephrectomy, desoxycorticosterone administration, and 1% saline in the drinking water. One group received recombinant human erythropoietin to increase hematocrit, and another group was subjected to phlebotomy and fed a low-iron diet to induce anemia. Control rats exhibited systemic and glomerular capillary hypertension, proteinuria, and substantial glomerular sclerosis at 8 wk. Erythropoietin modestly increased hematocrit and blood pressure and substantially aggravated glomerular capillary pressure, proteinuria, and glomerular sclerosis. In contrast, reduction of hematocrit with a low-iron diet significantly attenuated systemic and glomerular hypertension, proteinuria, and sclerosis. It was concluded that the pace of progression of glomerular injury can be limited by chronic reduction in hematocrit, which effectively ameliorates both systemic and glomerular hypertension in this model of salt-sensitive hypertensive renal disease.

Physiological and structural responses to chronic experimental renal allograft injury

1994 ◽  
Vol 267 (6) ◽  
pp. F1102-F1106 ◽  
Author(s):  
A. Junaid ◽  
S. M. Kren ◽  
M. E. Rosenberg ◽  
K. A. Nath ◽  
T. H. Hostetter
Keyword(s):  
Chronic Rejection ◽  
Renal Allograft ◽  
Donor Organ ◽  
Glomerular Capillary ◽  
Protein Excretion ◽  
Interstitial Volume ◽  
Number Of Patients ◽  
Injury Mechanisms ◽  
Structural Responses ◽  
Glomerular Capillary Hypertension

Chronic rejection necessitates a return to dialysis or retransplantation for a significant number of patients with renal allografts. Although alloresponses between donor organ and recipient importantly determine this process, the detailed immunologic processes and organ physiology of chronic rejection are unclear; in consequence its mechanism and therapy are uncertain. A model of chronic rejection in the rat was used to examine several facets of this process. Fisher-to-Lewis (F-L), allogeneic, and Lewis-to-Lewis (L-L), syngeneic, renal transplants were performed in nephrectomized recipients. All rats were treated with cyclosporin A (5 mg.kg-1.day-1) for 10 days from the time of grafting. At 6 wk, allogeneically grafted animals had a higher protein excretion rate (F-L, 47 +/- 30 mg/day; L-L, 17 +/- 6 mg/day; P <0.05) and an increase in glomerular capillary pressure (F-L, 69 +/- 5 mmHg; L-L, 58 +/- 8 mmHg; P <0.05) and fractional cortical interstitial volume (F-L, 29.8 +/- 4.3%; L-L, 19.5 +/- 4.0%; P < 0.01). This model of chronic rejection is characterized by glomerular capillary hypertension, proteinuria, and cortical interstitial expansion. Because these findings are also present in other models of chronic renal injury, mechanisms in addition to alloresponses may operate in chronic rejection.

Recovery of Damaged Glomerular Capillary Network with Endothelial Cell Apoptosis in Experimental Proliferative Glomerulonephritis

Nephron ◽  
1998 ◽  
Vol 79 (2) ◽  
pp. 206-214 ◽  
Author(s):  
Akira Shimizu ◽  
Yukinari Masuda ◽  
Hiroshi Kitamura ◽  
Masamichi Ishizaki ◽  
Yuichi Sugisaki ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Capillary Network ◽  
Proliferative Glomerulonephritis ◽  
Endothelial Cell Apoptosis ◽  
Glomerular Capillary

scholarly journals Pathogenesis of glomerular injury in the fawn-hooded rat: early glomerular capillary hypertension predicts glomerular sclerosis.

1993 ◽  
Vol 3 (11) ◽  
pp. 1775-1782 ◽  
Author(s):  
J L Simons ◽  
A P Provoost ◽  
S Anderson ◽  
J L Troy ◽  
H G Rennke ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Rapid Development ◽  
Systemic Hypertension ◽  
Glomerular Sclerosis ◽  
Hydraulic Pressure ◽  
Glomerular Capillary ◽  
Morphological Studies ◽  
Glomerular Capillary Hypertension ◽  
Segmental Glomerular Sclerosis

Fawn-hooded rats spontaneously develop focal and segmental glomerular sclerosis, systemic hypertension, and proteinuria at a young age. Micropuncture and morphological studies were performed in two inbred strains of fawn-hooded rats, FHH and FHL, with different susceptibilities to develop chronic renal failure. FHH rats have higher values for systolic blood pressure and proteinuria and more rapid development of focal and segmental glomerular sclerosis and subsequent chronic renal failure as compared with genetically closely related FHL rats. FHH and FHL strains and a Wistar control strain, WAG, were matched for age and were studied at 16 wk. FHH, FHL, and WAG-old (WAG-O) strains were matched for weight, and the last group was studied at 22 wk. WAG were also matched for weight to a young group of FHH rats (FHH-Y), and these were studied at 8 wk. In comparison with WAG and WAG-O rats, FHH and FHH-Y rats exhibited an increased in mean glomerular capillary hydraulic pressure (WAG, 52 +/- 1 mm Hg; WAG-O, 47 +/- 2 mm Hg; FHH, 60 +/- 2 mm Hg; FHH-Y, 65 +/- 1 mm Hg), whereas values in FHL animals were intermediate (56 +/- 2 mm Hg). No significant differences in glomerular volume were found among groups. Moderate focal and segmental glomerular sclerosis developed in FHH and FHH-Y rats, with values for older FHH rats being significantly greater than those for WAG, WAG-O, and FHL animals. Thus, the genetically determined sensitivity to develop proteinuria, focal and segmental glomerular sclerosis, and chronic renal failure in fawn-hooded rats correlated with early evidence of glomerular capillary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanical strain increases SPARC levels in podocytes: implications for glomerulosclerosis

2005 ◽  
Vol 289 (3) ◽  
pp. F577-F584 ◽  
Author(s):  
Raghu V. Durvasula ◽  
Stuart J. Shankland
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Mechanical Strain ◽  
Early Event ◽  
Matricellular Protein ◽  
Podocyte Injury ◽  
Whole Cell Lysate ◽  
Cell Lysate ◽  
Glomerular Capillary ◽  
Glomerular Capillary Hypertension ◽  
Cyclical Stretch

Glomerular capillary hypertension is a final common pathway to glomerulosclerosis. Because podocyte loss is an early event in the development of glomerulosclerosis, it is logical that the deleterious effects of glomerular capillary hypertension involve podocyte injury. Yet, the mechanisms by which elevated intraglomerular pressure is translated into a maladaptive podocyte response remain poorly understood. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein activated in various disease states of the podocyte and accelerates renal injury, as evidenced by the milder course of experimental diabetic nephropathy in SPARC-null mice compared with diabetic SPARC wild-type mice. Accordingly, we tested the hypothesis that mechanical strain activates SPARC in podocytes and thus is a putative mediator of podocyte injury in states of intraglomerular capillary hypertension. Conditionally immortalized mouse podocytes were subjected to 10% cyclical stretch while nonstretched cells served as controls. SPARC levels were measured in whole cell lysate and cell media. Immunostaining was performed for SPARC in an experimental model of glomerular capillary hypertension. Our results demonstrate cyclical stretch of podocytes markedly increased SPARC levels in cell lysate, through activation of p38, as well as secreted SPARC. Relevance was shown by demonstrating increased podocyte staining for SPARC in the uninephrectomized spontaneously hypertensive rat. In conclusion, we have made the novel observation that mechanical forces characteristic of states of glomerular capillary hypertension lead to increased levels of SPARC in podocytes. We speculate that the increase in SPARC may be maladaptive and lead to a progressive reduction in podocyte number, thus fueling the future development of glomerulosclerosis.

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