Pathobiology of focal sclerosis

This morphologic and morphometric study of native-kidney biopsies of six homozygous sickle hemoglobin (SS) nephrotics defines a distinctive glomerulopathy of focal sclerosis developing in maximally hypertrophied glomeruli. In each biopsy, two patterns of segmental glomerulosclerosis were observed: a "collapsing" pattern and an "expansive" pattern. Morphologic analysis comparing group mean glomerular (Bowman's capsular) diameters indicates that glomeruli in SS are routinely markedly enlarged whether nephrotic (group SSN, 233.6 mu +/- SE of 25.3 [N = 6]) or not (control group SSC, 243.5 mu +/- SE of 12.5 [N = 5]). These values are significantly larger when compared with those of matched normal controls (group NC, 158.0 mu +/- SE of 12.7 [N = 6]) or to matched patients with idiopathic focal glomerulosclerosis (group IFS, 188.2 mu +/- SE of 17.9 [N = 6]). Furthermore, based on a previous study, it is most likely that glomerular enlargement in SS represents the maximal hypertrophy attainable in humans. Correlating observations of renal homografts in two sickle hemoglobin patients that developed segmental sclerosis of only the collapsing pattern soon after transplantation, it is proposed that in homozygous sickle hemoglobin nephrotics the collapsing pattern of segmental glomerulosclerosis represents an initial but progressive obliteration of the glomerular capillary bed by red blood cell sickling which cannot be compensated by further glomerular hypertrophy. Hemodynamic glomerular injury then supervenes from the sustained or increasing hyperfiltration in a diminishing capillary bed, manifesting morphologically as the expansive pattern of sclerosis.

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PATHOMORPHOLOGICAL CHARACTERISTICS OF IMMUNOCOMPLEX RENAL DISEASE IN PATIENTS WITH IMMUNODEFICIENCY VIRUS AND HEPATITIS C VIRUS, RECEIVING ANTIRETROVIRAL THERAPY

Wiadomości Lekarskie ◽

10.36740/wlek202107102 ◽

2021 ◽

Vol 74 (7) ◽

pp. 1552-1558

Author(s):

Anna I. Gorodetska ◽

Olena O. Dyadyk ◽

Mariia D. Ivanova ◽

Nana M. Pasiyeshvili

Keyword(s):

Renal Disease ◽

Morphological Changes ◽

Single Cells ◽

Kidney Tissue ◽

Kidney Damage ◽

Tissue Samples ◽

Immunodeficiency Virus ◽

Matrix Expansion ◽

Focal Sclerosis ◽

Diffuse Mesangial Proliferation

The aim is to verify and describe the morphological substrate of renal impairment in HIV/HCV co-infection among patients receiving ART to assess and predict the morphogenesis of immunocomplex lesions. Materials and methods: To assess and predict the morphogenesis of immunocomplex renal disease, we examined retrospectively the kidney tissue samples of 15 patients, who died with HIV/HCV co-infection and received ART. Histological, histochemical and immunohistochemical research methods were used. Results: Segmental and diffuse mesangial proliferation with extracellular matrix expansion with glomerular damage ≥50% in 9 (60%) cases, and involving <50% of glomeruli in 5 (33%), with CD68 expression as single cells were detected. In 12 (80%) cases, there was uneven swelling and focal proliferation of endothelial cells with the involvement of 20-50% of the glomeruli, as well as the presence of cellular infiltrates in the lumen of capillary loops in 3 (20%) cases with monomorphic intensity in “+”. Sclerotic changes were present in various degrees of severity – from cases of complete glomerulosclerosis with obliteration of the Bowman’s lumen to focal and microfocal depressions 8 (55%), sclerosis 10 (66%), hyalinosis 1 (6%), uneven thickening, focal cleft 8 (55%) and perihilar focal sclerosis. These areas were positive for IgG and C1q complement fractions within the “+”, “++” intensity. Among the study group, no case of HIV-associated nephropathy was found that coincided with the predicted spectrum of kidney damage for patients in this sample. The described morphological changes were mainly verified as immuno-mediated by HCV. Conclusions: A comprehensive morphological study revealed the morphological substrate of kidney damage and its morphogenesis in patients with HIV/HCV co-infection, receiving ART.

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Adhesions, focal sclerosis, protein crescents, and capsular lesions in membranous nephropathy

The Journal of Pathology ◽

10.1002/path.1711610109 ◽

1990 ◽

Vol 161 (1) ◽

pp. 47-56 ◽

Cited By ~ 26

Author(s):

B. Van Damme ◽

R. Tardanico ◽

Y. Vanrenterghem ◽

V. Desmet

Keyword(s):

Membranous Nephropathy ◽

Focal Sclerosis

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Lipoid Nephrosis and Focal Sclerosis Distinct Entities or Spectrum of Disease

Nephron ◽

10.1159/000180382 ◽

1974 ◽

Vol 13 (2) ◽

pp. 105-108 ◽

Cited By ~ 17

Author(s):

Michael Kashgarian ◽

John P. Hayslett ◽

Norman J. Siegel

Keyword(s):

Focal Sclerosis

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Morphologic and functional consequences of immune-mediated mesangiolysis: development of chronic glomerular sclerosis.

Journal of the American Society of Nephrology ◽

10.1681/asn.v210s144 ◽

1992 ◽

Vol 2 (10) ◽

pp. S144

Author(s):

R A Stahl ◽

F Thaiss ◽

U Wenzel ◽

U Helmchen

Keyword(s):

Blood Pressure ◽

Arterial Blood Pressure ◽

Damage Index ◽

Glomerular Sclerosis ◽

Arterial Blood ◽

Immune Mediated ◽

Glomerular Lesions ◽

Proliferative Lesion ◽

Functional Consequences ◽

Focal Sclerosis

The i.v. injection of a rabbit anti-rat thymocyte serum (ATS) induces mesangiolysis in rats, followed by a mesangioproliferative glomerulonephritis (4 to 7 days after antibody). This proliferative lesion disappears 4 to 6 wks after antibody. In order to induce an antibody-mediated sclerotic glomerular disease, uninephrectomized rats received ATS twice at 6-wk interval. At 6 months after the first antibody injection, albuminuria, arterial blood pressure, and inulin clearances were evaluated and renal morphologic studies were performed. At the time of evaluation, mean arterial blood pressure and inulin clearances were not different between animals that received the antibody and uninephrectomized controls. Rats that were injected with antibody, however, had significantly higher albuminuria compared with that of controls. Glomeruli of rats with ATS revealed expansion of the glomerular mesangial matrix and focal sclerosis. A semiquantitative morphologic analysis revealed an increased incidence of glomerular lesions and a higher glomerular damage index in kidneys of nephritic rats. These data demonstrate that the repetitive injection of ATS to unilaterally nephrectomized rats induces a model of chronic glomerular sclerosis.

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Identification of membrane-bound CR1 (CD35) in human urine: evidence for its release by glomerular podocytes.

Journal of Experimental Medicine ◽

10.1084/jem.179.3.889 ◽

1994 ◽

Vol 179 (3) ◽

pp. 889-899 ◽

Cited By ~ 57

Author(s):

M Pascual ◽

G Steiger ◽

S Sadallah ◽

J P Paccaud ◽

J L Carpentier ◽

...

Keyword(s):

Molecular Mass ◽

Lupus Erythematosus ◽

Gel Filtration ◽

Sucrose Density Gradient ◽

Apparent Size ◽

Soluble Form ◽

Focal Sclerosis ◽

Membrane Bound ◽

The Difference ◽

Normal Urine

Complement receptor 1 (CR1) is present on erythrocytes (E-CR1), various leucocytes, and renal glomerular epithelial cells (podocytes). In addition, plasma contains a soluble form of CR1 (sCR1). By using a specific ELISA, CR1 was detected in the urine (uCR1) of normal individuals (excretion rate in 12 subjects, 3.12 +/- 1.15 micrograms/24 h). Contrary to sCR1, uCR1 was pelleted by centrifugation at 200,000 g for 60 min. Analysis by sucrose density gradient ultracentrifugation showed that uCR1 was sedimenting in fractions larger than 19 S, whereas sCR1 was found as expected in fractions smaller than 19 S. The addition of detergents reduced the apparent size of uCR1 to that of sCR1. After gel filtration on Sephacryl-300 of normal urine, the fractions containing uCR1 were found to be enriched in cholesterol and phospholipids. The membrane-association of uCR1 was demonstrated by analyzing immunoaffinity purified uCR1 by electron microscopy which revealed membrane-bound vesicles. The apparent molecular mass of uCR1 was 15 kD larger than E-CR1 and sCR1 when assessed by SDS-PAGE and immunoblotting. This difference in size could not be explained on the basis of glycosylation only, since pretreatment with N-glycosidase F reduced the size of all forms of CR1; however, the difference in regular molecular mass was not abrogated. The structural alleles described for E-CR1 were also found for uCR1. The urine of patients who had undergone renal transplantation contained alleles of uCR1 which were discordant with E-CR1 in 7 of 11 individuals, indicating that uCR1 originated from the kidney. uCR1 was shown to bind C3b-coated immune complexes, suggesting that the function of CR1 was not destroyed in urine. A decrease in uCR1 excretion was observed in 3 of 10 patients with systemic lupus erythematosus, corresponding to the three who had severe proliferative nephritis, and in three of three patients with focal sclerosis, but not in six other patients with proteinuria. Taken together, these data suggest that glomerular podocytes release CR1-coated vesicles into the urine. The function of this release remains to be defined, but it may be used as a marker for podocyte injury.

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