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  1. Article ; Online: Hyaline arteriolosclerosis associated paratubular basement membrane insudative lesions in distal renal tubules.

    Mii, Akiko / Tagawa, Masako / Endo, Yoko / Shimizu, Akira / Terasaki, Mika

    Clinical and experimental nephrology

    2021  Volume 25, Issue 10, Page(s) 1158–1160

    MeSH term(s) Arteriolosclerosis ; Arteriosclerosis ; Basement Membrane/pathology ; Humans ; Hyalin ; Kidney Tubules/pathology ; Kidney Tubules, Distal/pathology
    Language English
    Publishing date 2021-06-07
    Publishing country Japan
    Document type Letter
    ZDB-ID 1338768-6
    ISSN 1437-7799 ; 1342-1751
    ISSN (online) 1437-7799
    ISSN 1342-1751
    DOI 10.1007/s10157-021-02076-x
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    Zs.A 4922: Show issues Location:
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  2. Article ; Online: Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis Superimposed on Post-streptococcal Acute Glomerulonephritis.

    Kamijo, Natsumi / Mii, Akiko / Aratani, Sae / Kashiwagi, Tetsuya / Oda, Takashi / Shimizu, Akira / Sakai, Yukinao

    Internal medicine (Tokyo, Japan)

    2022  Volume 61, Issue 19, Page(s) 2917–2923

    Abstract: A 44-year-old woman was admitted due to gross hematuria and progressive renal dysfunction. Poststreptococcal acute glomerulonephritis (PSAGN) was suspected due to her elevated anti-streptolysin O and anti-streptokinase titers and hypocomplementemia. A ... ...

    Abstract A 44-year-old woman was admitted due to gross hematuria and progressive renal dysfunction. Poststreptococcal acute glomerulonephritis (PSAGN) was suspected due to her elevated anti-streptolysin O and anti-streptokinase titers and hypocomplementemia. A renal biopsy showed crescent formation and endocapillary hypercellularity with neutrophil infiltrate. An immunofluorescence analysis showed granular immunoglobulin G and C3 deposition, suggesting immune-complex-type glomerulonephritis. However, myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA) was positive, and peritubular capillaritis was observed. Furthermore, citrullinated histone H3-positive neutrophils were detected as markers for neutrophil extracellular trap formation. Therefore, she was diagnosed with ANCA-associated vasculitis superimposed on PSAGN that was the main contributor to her progressive renal injury.
    MeSH term(s) Acute Disease ; Adult ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ; Antibodies, Antineutrophil Cytoplasmic ; Female ; Glomerulonephritis/complications ; Glomerulonephritis/diagnosis ; Histones ; Humans ; Immunoglobulin G ; Peroxidase
    Chemical Substances Antibodies, Antineutrophil Cytoplasmic ; Histones ; Immunoglobulin G ; Peroxidase (EC 1.11.1.7)
    Language English
    Publishing date 2022-03-12
    Publishing country Japan
    Document type Case Reports ; Journal Article
    ZDB-ID 32371-8
    ISSN 1349-7235 ; 0021-5120 ; 0918-2918
    ISSN (online) 1349-7235
    ISSN 0021-5120 ; 0918-2918
    DOI 10.2169/internalmedicine.8690-21
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    Zs.A 240: Show issues Location:
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  3. Article ; Online: Predominant CD8

    Tominaga, Kenta / Toda, Etsuko / Takeuchi, Kazuhiro / Takakuma, Shoichiro / Sakamoto, Emi / Kuno, Hideaki / Kajimoto, Yusuke / Terasaki, Yasuhiro / Kunugi, Shinobu / Mii, Akiko / Sakai, Yukinao / Terasaki, Mika / Shimizu, Akira

    Pathology international

    2024  

    Abstract: Immune checkpoint inhibitors (ICIs) can provide survival benefits to cancer patients; however, they sometimes result in the development of renal immune-related adverse events (irAEs). Tubulointerstitial nephritis (TIN) is the most representative ... ...

    Abstract Immune checkpoint inhibitors (ICIs) can provide survival benefits to cancer patients; however, they sometimes result in the development of renal immune-related adverse events (irAEs). Tubulointerstitial nephritis (TIN) is the most representative pathological feature of renal irAEs. However, the clinicopathological entity and underlying pathogenesis of ICI-induced TIN are unclear. Therefore, we compared the clinical and histological features of this condition with those of non-ICI drug-induced TIN. Age and C-reactive protein levels were significantly higher in ICI-induced TIN, but there were no significant differences in renal function. Immunophenotyping of ICI-induced TIN showed massive T cell and macrophage infiltration with fewer B cells, plasma cells, neutrophils, and eosinophils. Compared with those in non-ICI drug-induced TIN, CD4
    Language English
    Publishing date 2024-04-18
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 1194850-4
    ISSN 1440-1827 ; 1320-5463
    ISSN (online) 1440-1827
    ISSN 1320-5463
    DOI 10.1111/pin.13428
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  4. Article ; Online: The severity of glomerular endothelial cell injury is associated with infiltrating macrophage heterogeneity in endocapillary proliferative glomerulonephritis.

    Arai, Momoko / Mii, Akiko / Kashiwagi, Tetsuya / Shimizu, Akira / Sakai, Yukinao

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 13339

    Abstract: Endocapillary proliferation occurs in various types of glomerulonephritis (GN), with varying prognoses. We examined 42 renal biopsy samples representing endocapillary proliferative lesions from post-streptococcal acute GN (PSAGN), Henoch-Schönlein ... ...

    Abstract Endocapillary proliferation occurs in various types of glomerulonephritis (GN), with varying prognoses. We examined 42 renal biopsy samples representing endocapillary proliferative lesions from post-streptococcal acute GN (PSAGN), Henoch-Schönlein purpura nephritis (HSPN), and lupus nephritis (LN). In PSAGN, the glomerular capillary network was maintained, although severe lesions displayed dots or short, curved lines, indicating CD34-positive capillaries and suggesting capillary obstruction. Conversely, patients with LN and HSPN displayed obstruction of CD34-positive capillaries with dissociation from the glomerular basement membrane even in mild lesions. According to computer-assisted morphologic analysis, the cell density did not differ between the diseases. However, in PSAGN, the number of capillary loops was significantly increased, with a larger glomerular capillary luminal area than in the other groups. In addition, the number and frequency of CD163-positive cells (M2 macrophages) tended to be higher in PSAGN, while there were no significant differences in the number of CD68-positive (total) macrophages. These results indicate that in PSAGN, endothelial cell damage is less severe, and angiogenesis may be promoted. The severity of endothelial cell injury in each disease may be associated with differences in infiltrating inflammatory cell phenotypes.
    MeSH term(s) Acute Disease ; Adolescent ; Adult ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Capillaries/metabolism ; Capillaries/pathology ; Child ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Female ; Glomerulonephritis, Membranoproliferative/metabolism ; Glomerulonephritis, Membranoproliferative/pathology ; Humans ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/pathology ; Lupus Nephritis/metabolism ; Lupus Nephritis/pathology ; Macrophages/metabolism ; Macrophages/pathology ; Male ; Middle Aged ; Prognosis ; Purpura, Schoenlein-Henoch/metabolism ; Purpura, Schoenlein-Henoch/pathology ; Receptors, Cell Surface/metabolism ; Young Adult
    Chemical Substances Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; CD163 antigen ; Receptors, Cell Surface
    Language English
    Publishing date 2021-06-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-92655-5
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  5. Article ; Online: Update on Recurrent Focal Segmental Glomerulosclerosis in Kidney Transplantation.

    Shoji, Jun / Mii, Akiko / Terasaki, Mika / Shimizu, Akira

    Nephron

    2020  Volume 144 Suppl 1, Page(s) 65–70

    Abstract: Background: Focal segmental glomerulosclerosis (FSGS) is a clinicopathological syndrome characterized by nephrotic-range proteinuria with high incidence of progression to end-stage renal disease (ESRD). In primary FSGS, 40-60% of patients develop ESRD ... ...

    Abstract Background: Focal segmental glomerulosclerosis (FSGS) is a clinicopathological syndrome characterized by nephrotic-range proteinuria with high incidence of progression to end-stage renal disease (ESRD). In primary FSGS, 40-60% of patients develop ESRD within 10-20 years.
    Summary: Recurrence of FSGS after kidney transplantation is frequent and is associated with poor allograft survival. The risk factors for recurrent FSGS include onset of FSGS during childhood, rapid progression of primary FSGS to ESRD, history of recurrent FSGS in previous allograft, and diffuse mesangial hypercellularity or collapsing variant of FSGS in the native kidney. The early histological findings of recurrent FSGS consist of unremarkable glomerular changes on light microscopy but significant podocyte effacement on electron microscopy; the loss of foot processes with eventual dropout of podocytes leads to the development of segmental lesions in the glomerulus. Experimental and clinical data suggest the existence of circulating permeability factors, such as soluble urokinase-type plasminogen activator receptor (suPAR), cardiotrophin-like cytokine factor-1 (CLCF-1), CD40 axis, and apolipoprotein A-Ib (ApoA-Ib), in the pathogenesis of recurrent FSGS. These biomarkers including circulating permeability factors may facilitate earlier diagnosis of FSGS posttransplant and may guide in the development of novel therapies that may be more effective and improve long-term outcomes in kidney transplantation. Key Messages: Several studies have suggested the possible circulating permeability factors, such as suPAR, CLCF-1, CD40 axis, and ApoA-Ib, in the pathogenesis and disease progression of FSGS and recurrent FSGS. Further studies should be performed to elucidate the true essential biomarker(s) associated with the onset and progression of FSGS as well as recurrent FSGS.
    MeSH term(s) CD40 Antigens/physiology ; CD40 Ligand/physiology ; Glomerular Filtration Barrier ; Glomerulosclerosis, Focal Segmental/etiology ; Glomerulosclerosis, Focal Segmental/pathology ; Humans ; Kidney Glomerulus/pathology ; Kidney Transplantation/adverse effects ; Postoperative Complications/etiology ; Postoperative Complications/pathology ; Recurrence
    Chemical Substances CD40 Antigens ; CD40 Ligand (147205-72-9)
    Language English
    Publishing date 2020-12-01
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 207121-6
    ISSN 2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
    ISSN (online) 2235-3186 ; 1423-0186
    ISSN 1660-8151 ; 0028-2766
    DOI 10.1159/000510748
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    Zs.A 169: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  6. Article ; Online: A possible role of classical complement pathway activation in the pathogenesis of immunoglobulin G nephropathy: a case report.

    Arai, Momoko / Mii, Akiko / Hirama, Akio / Kaneko, Tomohiro / Kashiwagi, Tetsuya / Shimizu, Akira / Sakai, Yukinao

    CEN case reports

    2022  Volume 12, Issue 1, Page(s) 14–22

    Abstract: Immunoglobulin G (IgG) nephropathy refers to a rare group of diseases characterized by deposits of IgG in the mesangial region. However, IgG nephropathy is controversial as a single disease entity, and its pathogenesis remains to be elucidated. In the ... ...

    Abstract Immunoglobulin G (IgG) nephropathy refers to a rare group of diseases characterized by deposits of IgG in the mesangial region. However, IgG nephropathy is controversial as a single disease entity, and its pathogenesis remains to be elucidated. In the present report, we discuss a case of IgG nephropathy in which we observed activation of the classical complement pathway.A 47-year-old woman was admitted to our hospital with nephrotic syndrome. Light-microscopic examination revealed neither proliferative nor sclerotic lesions in the glomeruli. However, unusual and large deposits were observed in the paramesangial area. An immunofluorescence study revealed predominant IgG and C1q and slight C3 deposits in the paramesangial area, suggesting immune-complex-type glomerular disease. An electron microscopic study also revealed different sizes of non-organized electron-dense deposits with a similar pattern of distribution, which were accompanied by foot process effacement. Clinically, there was no evidence of systemic diseases, such as infectious or autoimmune diseases (including systemic lupus erythematosus). Based on these findings, she was diagnosed with IgG nephropathy and treated with prednisolone. Steroid therapy was effective, and complete remission was maintained.Additional immunological examination revealed that IgG deposits were polyclonal and consisted mainly of the IgG1 and IgG3 subclasses. Furthermore, staining was positive for C4d and C5b-9. The present findings indicate that the pathogenesis of IgG nephropathy in our patient may have involved activation of the classical complement pathway.
    MeSH term(s) Female ; Humans ; Middle Aged ; Immunoglobulin G ; Complement Pathway, Classical ; Kidney Glomerulus/pathology ; Nephrotic Syndrome/diagnosis ; Nephrotic Syndrome/etiology ; Nephrotic Syndrome/pathology ; Glomerular Mesangium/pathology
    Chemical Substances Immunoglobulin G
    Language English
    Publishing date 2022-06-16
    Publishing country Japan
    Document type Case Reports ; Journal Article
    ZDB-ID 2660492-9
    ISSN 2192-4449 ; 2192-4449
    ISSN (online) 2192-4449
    ISSN 2192-4449
    DOI 10.1007/s13730-022-00710-5
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  7. Article ; Online: Diverse Alterations of Glomerular Capillary Networks in Focal Segmental Glomerular Sclerosis.

    Morita, Megumi / Mii, Akiko / Yasuda, Fumihiko / Arakawa, Yusuke / Kashiwagi, Tetsuya / Shimizu, Akira

    Kidney international reports

    2022  Volume 7, Issue 6, Page(s) 1229–1240

    Abstract: Introduction: Focal segmental glomerular sclerosis (FSGS) is caused by podocyte injury. It is characterized by obliteration of glomerular capillary tufts with increased extracellular matrix (ECM). Altered communication between podocytes and glomerular ... ...

    Abstract Introduction: Focal segmental glomerular sclerosis (FSGS) is caused by podocyte injury. It is characterized by obliteration of glomerular capillary tufts with increased extracellular matrix (ECM). Altered communication between podocytes and glomerular endothelial cells (ECs) contributes to sclerosis progression. We focused on EC injury in the FSGS.
    Methods: A total of 29 FSGS and 18 control biopsy specimens were assessed for clinicopathologic characteristics. CD34 (a marker for EC)-positive capillaries and ECM accumulation were evaluated quantitatively for each variant using computer-assisted image analysis.
    Results: The estimated glomerular filtration rate (eGFR) in the FSGS group was significantly lower than that in the control group. The frequency of FSGS variants was 51.7% for cellular; 13.8% for perihilar (PH), tip, and not otherwise specified (NOS); and 6.9% for collapsing. Regarding sclerotic lesions in all FSGS, narrowing or loss of CD34-positive capillaries was observed. Electron microscopy results showed loss of fenestrae, subendothelial space enlargement, and cytoplasmic swelling, indicating EC injury. Computer-assisted image analysis revealed significantly smaller areas of glomerular capillaries in FSGS with or without sclerotic lesions, with increased ECM. Moreover, in comparison with each variant, narrowed capillaries and ECM accumulation were most prominent in the collapsing variant, whereas the tip variant had the least change.
    Conclusion: EC injury was observed in all FSGS cases, not only in sclerotic lesions but also in nonsclerotic lesions. Severity of EC injury may vary in each variant due to diverse alterations of glomerular capillary networks.
    Language English
    Publishing date 2022-03-14
    Publishing country United States
    Document type Journal Article
    ISSN 2468-0249
    ISSN (online) 2468-0249
    DOI 10.1016/j.ekir.2022.03.007
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  8. Article ; Online: A case of proliferative glomerulonephritis with monoclonal IgG3κ deposits accompanied by glomerular capillary microaneurysms.

    Mii, Akiko / Terasaki, Mika / Kunugi, Shinobu / Seki, Miyako / Kashiwagi, Tetsuya / Sakai, Yukinao / Shimizu, Akira

    CEN case reports

    2022  Volume 11, Issue 3, Page(s) 333–338

    Abstract: Glomerular capillary aneurysms are distinctly rare and specific glomerular lesions characterized by aneurysmal dilatation of the glomerular capillaries. This formation is associated with glomerular capillary injuries with focal mesangiolysis. Here, we ... ...

    Abstract Glomerular capillary aneurysms are distinctly rare and specific glomerular lesions characterized by aneurysmal dilatation of the glomerular capillaries. This formation is associated with glomerular capillary injuries with focal mesangiolysis. Here, we report a case of proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) presenting with multiple glomerular capillary microaneurysms. A 53-year-old woman presented with persistent proteinuria and microhematuria. She had no underlying diseases, such as hematopoietic or lymphoproliferative disorders. A renal biopsy showed diffuse membranoproliferative lesions with foam cell infiltration and multiple microaneurysms of the glomerular capillary on light microscopy. Immunofluorescence analysis showed granular deposits of monoclonal immunoglobulin G3 kappa (IgG3κ), C1q, C3, and C4 in the glomeruli. Electron microscopy revealed different sizes of non-organized electron-dense deposits in the mesangial, subendothelial, and subepithelial areas. In addition, glomerular endothelial cells showed swelling and loss of fenestra or diffuse formation of fenestrated diaphragms, accompanied by irregular thinning of the glomerular basement membrane. Furthermore, immunostaining for CD31 (a marker for endothelial cell) and low-vacuum scanning electron microscopy study identified loss of endothelial cells in microaneurysm, suggesting severe glomerular endothelial cell injury. After a renal biopsy, only the medication for dyslipidemia was continued because there were no physical symptoms, such as edema, and urinary abnormalities continued with stable renal function. Further studies are needed to elucidate the pathogenesis of glomerular capillary injury in PGNMID and clarify the clinical and pathological characteristics of PGNMID with glomerular capillary microaneurysms.
    MeSH term(s) Antibodies, Monoclonal ; Endothelial Cells/chemistry ; Endothelial Cells/pathology ; Female ; Glomerular Basement Membrane/pathology ; Glomerulonephritis/diagnosis ; Glomerulonephritis/pathology ; Humans ; Immunoglobulin G/analysis ; Immunoglobulin kappa-Chains ; Microaneurysm ; Middle Aged
    Chemical Substances Antibodies, Monoclonal ; Immunoglobulin G ; Immunoglobulin kappa-Chains
    Language English
    Publishing date 2022-01-13
    Publishing country Japan
    Document type Case Reports ; Journal Article
    ZDB-ID 2660492-9
    ISSN 2192-4449 ; 2192-4449
    ISSN (online) 2192-4449
    ISSN 2192-4449
    DOI 10.1007/s13730-021-00676-w
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  9. Article ; Online: Concomitant Anti-GBM Glomerulonephritis and Acute Interstitial Nephritis Following Programmed Death Receptor-1 Blockade With Nivolumab.

    Tani, Takashi / Sugino, Kenta / Hashimoto, Kazumasa / Mii, Akiko / Kashiwagi, Tetsuya / Shimizu, Akira / Sakai, Yukinao / Iwabu, Masato

    Kidney international reports

    2022  Volume 7, Issue 10, Page(s) 2317–2318

    Language English
    Publishing date 2022-08-29
    Publishing country United States
    Document type Journal Article
    ISSN 2468-0249
    ISSN (online) 2468-0249
    DOI 10.1016/j.ekir.2022.08.020
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  10. Article ; Online: Development of angiogenic periglomerular microvessels after acute glomerular lesions in IgA nephropathy.

    Kamano, Chisako / Mii, Akiko / Osono, Eiichi / Kunugi, Shinobu / Igarashi, Toru / Yanagihara, Takeshi / Kaneko, Tomohiro / Terasaki, Mika / Shimizu, Akira

    Histopathology

    2023  Volume 83, Issue 4, Page(s) 617–630

    Abstract: Aim: To clarify the clinicopathological characteristics and role of periglomerular angiogenesis in IgA nephropathy.: Methods and results: The renal biopsy specimens of 114 patients with IgA nephropathy were examined. Among them, 46 (40%) showed ... ...

    Abstract Aim: To clarify the clinicopathological characteristics and role of periglomerular angiogenesis in IgA nephropathy.
    Methods and results: The renal biopsy specimens of 114 patients with IgA nephropathy were examined. Among them, 46 (40%) showed periglomerular angiogenesis around the glomeruli. CD34 and α-smooth muscle actin (α-SMA) staining in serial sections revealed that these vessels contained CD34+ α-SMA+ microarterioles along with CD34+ α-SMA- capillaries. We termed these "periglomerular microvessels (PGMVs)". Patients with PGMVs (PGMV group) had clinically and histologically more severe disease than those without PGMVs (non-PGMV group) at the time of biopsy. Even after adjusting for age, there were significant differences in the degree of proteinuria and estimated glomerular filtration rate reduction between the PGMV and non-PGMV groups. The PGMV group showed a higher incidence of segmental and global glomerulosclerosis and crescentic lesions than the non-PGMV group (P < 0.01). Here, PGMVs were undetectable in the acute and active inflammation phase, but were observed in the acute to chronic or chronic glomerular remodelling phase. PGMVs mainly developed around glomerular adherent lesions to the Bowman's capsule with small or minimal glomerular sclerotic lesions. Conversely, they were rarely observed in segmental sclerosis areas.
    Conclusion: The PGMV group is clinically and pathologically more severe than the non-PGMV group; however, they were undetectable in segmental sclerosis with mesangial matrix accumulation. PGMVs might occur after acute/active glomerular lesions, suggesting that PGMVs may inhibit segmental glomerulosclerosis progression and could be a marker for good repair response after acute/active glomerular injury in severe IgA nephropathy cases.
    MeSH term(s) Humans ; Glomerulonephritis, IGA/pathology ; Sclerosis/pathology ; Kidney Glomerulus/pathology ; Glomerulosclerosis, Focal Segmental/pathology ; Biopsy ; Capillaries/pathology
    Language English
    Publishing date 2023-06-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 131914-0
    ISSN 1365-2559 ; 0309-0167
    ISSN (online) 1365-2559
    ISSN 0309-0167
    DOI 10.1111/his.14997
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