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PubMed2005

Vascular endothelial growth factor (VEGF-C1)-dependent inflammatory response of podocytes in nephrotic syndrome glomerulopathies in children: an immunohistochemical approach.

AIMS: To analyse expression and distribution of vascular endothelial growth factor (VEGF-C1), podocalyxin and synaptopodin within renal tissue in nephrotic syndrome glomerulopathies in children. METHODS AND RESULTS: Renal biopsies performed at the time and in the manner recommended by the World Health Organization. The study group consisted of submicroscopic glomerulonephritis (n = 10), diffuse mesangial proliferation (n = 14) and focal segmental glomerulosclerosis (n = 5). The control tissue consisted of macroscopically normal appearing cortex taken from kidneys resected for localized neoplasms (n = 3). Material for immunohistochemistry was fixed in Bouin's solution and embedded in paraffin. Indirect immunohistochemistry using monoclonal anti-human antibodies directed against VEGF-C1, podocalyxin and synaptopodin was employed. The distribution of markers was quantified by computerized image analysis. In non-sclerosed glomeruli (within podocyte cytoplasm), VEGF-C1 was more expressed in podocytes of all groups (P < 0.0002), while the distribution of synaptopodin was less expressed in all groups (P < 0.0002). There was no statistical difference between all groups in the expression of podocalyxin. CONCLUSIONS: The increased permeability of the filtration barrier in steroid-resistant glomerulopathies may be a consequence of subcellular changes in podocytes resulting from decreased expression of synaptopodin. Moreover, impaired permeability of endothelium could be secondary to increased expression of podocyte-derived VEGF-C1.

Analysis of Variance↗
PubMed1997

Slit diaphragm-reactive nephritogenic MAb 5-1-6 alters expression of ZO-1 in rat podocytes.

Monoclonal antibody (MAb) 5-1-6 identifies a 51-kDa protein (p51) on rat podocyte foot processes and causes severe complement- and leukocyte-independent proteinuria when injected into rats. In the studies reported here, we used various immunohistological techniques to define the precise location of p51 and its relationship to ZO-1, a known component of the podocyte slit diaphragm in adult rat glomeruli. Our results demonstrate that p51 and ZO-1 lie close to each other on opposite sides of the podocyte plasma membrane at the point of insertion of the slit diaphragm: ZO-1 on the cytoplasmic face and p51 on the slit diaphragm and adjoining outer leaflet of the plasma membrane bordering the filtration slits. In addition to their geographic proximity, there appears to be a relationship between p51 and ZO-1. After MAb 5-1-6 injection, there was a progressive decline in stainable ZO-1 in the podocytes of heavily proteinuric rats. In addition, Western blot analysis of glomerular lysates showed that the decline in staining was due to a loss of immunoreactive ZO-1 rather than redistribution or diffusion of the protein. Simultaneously, the distribution of glomerular-bound MAb 5-1-6 became more clumped, apparently because of partial endocytosis into a lysosomal compartment, while the slit diaphragms remained morphologically intact. These findings suggest that MAb 5-1-6 alters the molecular composition of the slit diaphragm and thereby affects the glomerular permeability barrier.

Animals↗
PubMed2001

Podocyte injury predicts prognosis in patients with iga nephropathy using a small amount of renal biopsy tissue.

To predict the progression in patients with IgA nephropathy, we analyzed glomerular lesions except for sclerosis, adhesion and/or crescents in 34 patients with this disease by morphometric analysis. Levels of urinary protein excretion (UP), creatinine clearance (Ccr), serum creatinine (sCr) and mean blood pressure (MBP) at the time of renal biopsy were used as the clinical parameters. The slope of 1/sCr was also used as a prognostic parameter. Renal specimens were obtained by echo-guided biopsy. In PAS-stained light microscopic renal sections, three mid sections of open glomeruli were selected and photographed. Stereologic estimation was performed as follows: absolute values of glomerular volume (V(G)), glomerular surface area (S(G)), podocyte and nonpodocyte cell number per glomerulus (N(G(pod)) and N(G(Non-pod))), glomerular surface area covered by one podocyte S(G)/N(G(pod))) and glomerular volume occupied by one nonpodocyte cell (V(G)/N(G(Non-pod))). There was a significant correlation between the levels of UP and the change of podocyte injury parameters (N(G(pod)) and S(G)/N(G(pod))) or N(G(Non-pod)). N(G(pod)) was negatively but S(G)/N(G(pod)) and N(G(Non-pod)) were positively correlated with UP. S(G)/N(G(pod)) or N(G(Non-pod)) was correlated with MBP. N(G(pod)), S(G)/N(G(pod)), N(G(Non-pod)), UP or MBP was significantly correlated with the slope of 1/sCr. High specificity was observed for N(G(pod)), S(G)/N(G(pod)) and MBP. High sensitivity was also observed for N(G(Non-pod)) and UP. It appears that podocyte injury might provide additional prognostic information in patients with IgA nephropathy.

Adolescent↗
PubMed2002

Eluate derived by extracorporal antibody-based immunoadsorption elevates the cytosolic Ca2+ concentration in podocytes via B2 kinin receptors.

BACKGROUND/AIM: Patients with idiopathic focal segmental glomerulosclerosis (FSGS) often develop a recurrence of the disease after kidney transplantation. In a number of FSGS patients, plasmapheresis and immunoadsorption procedures have been shown to transiently reduce proteinuria and are thought to do this by eliminating a circulating factor. Direct cellular effects of eluates from immunoadsorption procedures on podocytes, the primary target of injury in FSGS, have not yet been reported. METHODS: Eluates were derived from antibody-based immunoadsorption of a patient suffering from primary FSGS, a patient with systemic lupus erythematosus, and a healthy volunteer. The cytosolic free Ca(2+) concentration ([Ca(2+)](i)) of differentiated podocytes was measured by single-cell fura-2 microfluorescence measurements. Free and total immunoreactive kinin levels were measured by radioimmunoassay. RESULTS: FSGS eluates increased the [Ca(2+)](i) levels concentration dependently (EC(50) 0.14 mg/ml; n = 3-19). 1 mg/ml eluate increased the [Ca(2+)](i) values reversibly from 82 +/- 12 to 1,462 +/- 370 nmol/l, and then they returned back to 100 +/- 16 nmol/l (n = 19). The eluate-induced increase of [Ca(2+)](i) consisted of an initial Ca(2+) peak followed by a Ca(2+) plateau which depended on the extracellular Ca(2+) concentration. The eluate-induced increase of [Ca(2+)](i) was inhibited by the specific B(2) kinin receptor antagonist Hoe 140 in a concentration-dependent manner (IC(50) 2.47 nmol/l). In addition, prior repetitive application of bradykinin desensitized the effect of eluate on [Ca(2+)](i). A colonic epithelial cell line not reacting to bradykinin did not respond to eluate either (n = 6). Similar to FSGS eluates, the eluate preparations of both the systemic lupus patient and the healthy volunteer led to a biphasic, concentration-dependent [Ca(2+)](i) increase in podocytes which again was inhibited by Hoe 140. Free kinins were detected in all eluate preparations. CONCLUSION: The procedure of antibody-based immunoadsorption leads to kinin in the eluate which elevates the [Ca(2+)](i) level of podocytes via B(2) kinin receptors.

Bradykinin↗
PubMed2004

Differentiation-induced cultured podocytes express endocytically active megalin, a heymann nephritis antigen.

BACKGROUND/AIMS: Megalin is a multiligand endocytic receptor expressed in a number of epithelia. In the Lewis rat kidney, podocytes, as well as proximal tubule cells, express megalin that acts as a pathogenic antigen for Heymann nephritis (HN), an experimental model of membranous nephropathy. To obtain a tool to investigate the molecular mechanisms of megalin-mediated endocytosis and the pathogenesis of HN, we examined whether a differentiation-inducible mouse podocyte cell line expressed endocytically active megalin. METHODS: Immunofluorescence and immunoprecipitation analyses with an anti-rat megalin antibody were carried out to investigate whether megalin was expressed in the differentiated and undifferentiated podocytes. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed to elucidate whether the cells synthesize megalin mRNA. 125I-labeled receptor-associated protein (RAP), an endocytic ligand for megalin, was used for cellular internalization and degradation assays. RESULTS: Immunofluorescence, immunoprecipitation and RT-PCR analyses revealed that megalin was synthesized in both differentiated and undifferentiated cells and localized to the cell surfaces. Effective endocytosis of RAP via megalin was shown under the differentiated condition. CONCLUSION: Endocytically active megalin is expressed in differentiation-induced cultured podocytes. This cell line could be a useful tool for studies on megalin-mediated endocytosis and the pathogenesis of HN.

Animals↗
PubMed2000

Altered podocyte structure in GLEPP1 (Ptpro)-deficient mice associated with hypertension and low glomerular filtration rate.

Glomerular epithelial protein 1 (GLEPP1) is a receptor tyrosine phosphatase present on the apical cell surface of the glomerular podocyte. The GLEPP1 gene (PTPRO:) was disrupted at an exon coding for the NH(2)-terminal region by gene targeting in embryonic stem cells. Heterozygote mating produced the expected genotypic ratio of 1:2:1, indicating that the Ptpro(-/-) genotype does not lead to embryonic or neonatal lethality. Kidney and glomerular structure was normal at the gross and light microscopic levels. Scanning and transmission electron microscopy showed that Ptpro(-/-) mice had an amoeboid rather than the typical octopoid structure seen in the wild-type mouse podocyte and that there were blunting and widening of the minor (foot) processes in association with altered distribution of the podocyte intermediate cytoskeletal protein vimentin. Reduced filtration surface area in association with these structural changes was confirmed by finding reduced glomerular nephrin content and reduced glomerular filtration rate in Ptpro(-/-) mice. There was no detectable increase in the urine albumin excretion of Ptpro(-/-) mice. After removal of one or more kidneys, Ptpro(-/-) mice had higher blood pressure than did their wild-type littermates. These data support the conclusion that the GLEPP1 (Ptpro) receptor plays a role in regulating the glomerular pressure/filtration rate relationship through an effect on podocyte structure and function.

Albumins↗
PubMed2005

Nephrotic plasma alters slit diaphragm-dependent signaling and translocates nephrin, Podocin, and CD2 associated protein in cultured human podocytes.

Podocytes are critical in maintaining the filtration barrier of the glomerulus and are dependent on the slit diaphragm (SD) proteins nephrin, podocin, and CD2-associated protein (CD2AP) to function optimally. The effects of normal human plasma and nephrotic plasma on podocytes were tested, focusing particularly on the SD complex. With the use of a conditionally immortalized human podocyte cell line, it first was shown that exposure to normal and non-nephrotic human plasma leads to a concentration of nephrin, podocin, CD2AP, and actin at the cell surface. Next, the effects of plasma from patients with nephrotic conditions to non-nephrotic conditions were compared. When exposed to all nephrotic plasma samples (and a non-human serum control), nephrin podocin and CD2AP assumed a cytoplasmic distribution; nephrin and synaptopodin were selectively downregulated, and the relocation of nephrin induced by nephrotic plasma could be rescued back to the plasma membrane by co-incubation with non-nephrotic plasma. Furthermore, intracellular calcium signaling was altered by nephrotic plasma, which was mediated by tyrosine kinase phosphorylation. With the use of nephrin mutant human cell lines, it was shown that this signaling and translocation response to normal plasma is nephrin dependent. This work demonstrates that nephrotic plasma seems to be deficient in factors that act via the podocyte SD complex, which are essential in maintaining its physiologic function.

Actins↗
PubMed2000

Localization of olfactomedin-related glycoprotein isoform (BMZ) in the golgi apparatus of glomerular podocytes in rat kidneys.

Agene encoding olfactomedin-related glycoprotein was isolated from rat glomerulus despite its prior identification as a neuron-specific gene. The mRNA expression was remarkably intense in renal glomerulus and brain and faint in the lung and eye among rat systemic organs. Although the brain contained four mRNA variants (AMY, AMZ, BMY, and BMZ) transcribed from a single gene, the glomerulus, lung, and eye expressed only two variants (BMZ and BMY). The glycoprotein was intensely immunolocalized in glomerular podocytes and neurons by using an antibody against synthetic peptide of the M region, but weak in endothelial cells of the kidney and lung. Bronchiolar epithelial cells in the lung, and ciliary, corneal, and iris epithelial cells in the eye were also stained. Immunogold electron microscopy revealed selective localization of olfactomedin-related glycoprotein at the Golgi apparatus in podocytes. In glomerular culture, the staining was also intense at a juxtanuclear region in synaptopodin-positive epithelial cells of irregular shape (phenotypic feature of podocytes), whereas it was weak in synaptopodin-negative ones of cobblestone-like appearance (phenotypic feature of parietal epithelial cells of Bowman's capsule). Interestingly, Western blot analysis identified an intense band corresponding to BMZ isoform and another faint band corresponding to BMY isoform in the glomerulus, whereas the intensity of these two bands were nearly equal in the lung and eye. In the brain, four bands corresponding to four isoforms were observed apparently. Computer sequence analysis predicted coiled-coil structures in the secondary structure of the glycoprotein similar to those in Golgi autoantigens, suggesting significant roles in the unique functions of the Golgi apparatus in rat podocytes and neurons.

Amino Acid Sequence↗
PubMed2002

Comparative effects of plasmapheresis and intravenous cyclophosphamide on urinary podocyte excretion in patients with proliferative Lupus nephritis.

Intravenous cyclophosphamide (IVC) in combination with steroids is standard therapy for Lupus nephritis. Reduction of autoantibodies and circulating immune complexes can be used in the treatment of autoimmune diseases. The aim of the present study was to compare the effects of IVC pulse therapy and double-filtration plasmapheresis (DFPP) on proteinuria and urinary excretion of podocytes in adult patients with diffuse proliferative Lupus nephritis (DPLN). Twenty patients were randomly assigned to two groups. Group A (n = 10) was treated with IVC (0.75 - 1.0 g/m2 body surface area) pulse therapy, given as boluses once a month for 6 consecutive months, combined with oral corticosteroid (up to 1 mg/kg/day) administration. Group B (n = 10) was treated with a combination of DFPP (performed 1-2 times weekly) and corticosteroid (up to I mg/kg/ day). The total average number of treatments was 8.4 and the therapeutic efficacies were evaluated after 6 months. Twenty healthy individuals participated as a control group. Urinary podocytes were examined by immunofluorescence with monoclonal antibodies against podocalyxin. Both Group A and Group B reduced proteinuria (p < 0.001) as well as the number of urinary podocytes (p < 0.001). Differences between the 2 treatment outcomes were not statistically significant. Cyclophosphamide pulse therapy and DFPP may be similarly effective in the treatment of podocyte injury in patients with DPLN.

Adult↗
PubMed2004

[Transforming growth factor beta 1 modulates connective tissue growth factor expression via Smad2 signaling pathway in podocyte in vitro].

OBJECTIVE: To assess the expression of connective tissue growth factor (CTGF), and the signaling pathway for the regulation of CTGF by transforming growth factor beta1 (TGF beta(1)) in podocytes. METHODS: In this study, we observed the effects of three potent profibrotic growth factors-TGF beta(1), Platelet-derived growth factor (PDGF), and Angiotensin II (AngII) on the expression of CTGF protein by Western blot analysis in cultured mouse podocytes, which is one of the most important cell construction of glomerular filter barrier, and we also investigated the underlying ERK and Smads signaling pathway through which TGF beta(1) regulates CTGF expression. The levels of CTGF mRNA were assayed by RT-PCR. RESULTS: Basal levels of CTGF protein were observed in cultured podocytes, treatment with 20 ng/ml PDGF and 10(-6) mol/L Ang. II for 24 h did not stimulate the expression of CTGF protein compared with control (P > 0.05), but significantly increase in levels of CTGF protein were seen in 1 ng/ml TGF beta(1) treated cells compared with with control (P < 0.05), and the levels of CTGF were up-regulated in a TGF beta(1) dose-dependent manner; The level of CTGF mRNA was also stimulated by 1 ng/ml TGF beta(1) at 12 h. 1 ng/ml TGF beta(1) induced phosphorylation of Smad(2) and ERK(1/2), and both reached the peak at 30 min; suppression of phosphorylation of Smad(2) with Staurosporine, a Serine/Threonine kinase inhibitor, diminished TGF beta(1)-triggered expression of CTGF protein, while blockade of phosphorylation of ERK(1/2) with PD98059, a specific ERK(1/2) activation inhibitor, did not decrease the TGF beta(1)-triggered expression of CTGF protein. CONCLUSION: TGF beta(1) stimulated the expression of CTGF protein via Smad(2)-dependent and ERK(1/2)-independent signaling pathway in podocyte in vitro.

Angiotensin II↗
PubMed1992

A case of IgA nephritis showing diffuse podocytic detachment from the glomerular basement membrane.

We report the case of a 15-year-old Japanese female with severe mesangial proliferative IgA glomerulonephritis who showed a dramatic response to cocktail therapy for nephrotic syndrome. She had suddenly developed massive proteinuria and microscopic hematuria. The first renal biopsy at one month after onset revealed severe mesangial hypercellularity and podocytic detachment from the glomerular basement membrane (GBM). The cocktail therapy resulted in a decrease of proteinuria clinically, and a second biopsy demonstrated repair of the podocytic detachment. We suggest that the massive proteinuria in this case was due to destruction of the size barrier by detachment of podocytes from the GBM, and the repair of the podocytic covering on the GBM was accelerated by the cocktail therapy.

Adolescent↗
PubMed1989

[Electron microscopic study of the cytoskeleton of human podocytes].

The ultrastructural study of man's cytoskeleton of podocytes is carried out. Populations of podocytes with two different types of structure of the cytoskeleton in dependence on age (2, 4, 6, 37 and 65 years) is revealed in kidneys. The first type of cytoskeleton of the podocyte is peculiar for children's age and is characterized by branched, high density microfilament network, expressed by system of microtubules and single myofilaments. The intermediate filaments here are either utterly absent or present so feebly they find themselves "disguised" by other strongly developed components of cytoskeleton and revealing them with the help of technique of electron microscope is impossible. In kidneys of adults, and especially of old aged persons podocytes with other type of organization of the cytoskeleton are mainly identified. The distinctive signs of the last are bundle arrangement of microfilaments, plural bundles of intermediate filaments and individual microtubules. This study permits to make a conclusion that during individual development and growing old in kidneys of high animals and man, probably, physiological changes causing morphological reconstruction of cytoskeleton which is accompanied by intensive development of intermediate filaments' system with simultaneous "involution" of microtubules and microfilaments' systems take place.

Actin Cytoskeleton↗
PubMed1984

Perturbation of podocyte plasma membrane domains in experimental nephrosis. A lectin-binding and freeze-fracture study.

Alterations in the ultrastructural organization of podocyte plasma membrane domains were quantitatively assessed in puromycin aminonucleoside-treated rats by the use of 1) Helix pomatia lectin-gold complexes for detection of a specific glycocalyx component(s) normally associated with foot process bases and 2) freeze-fracture for detection of intramembrane particles and endocytotic invaginations on the plasma membrane. Lectin-binding sites were significantly reduced on podocyte foot process bases during the 7-day treatment period; and in freeze-fracture, the plasma membrane of the foot process base showed an increase in intramembrane particle number and size and an increased number of endocytotic invaginations, compared with the numbers in control animals. The cell body of nephrotic animals also had a significantly increased intramembrane particle density, compared with the control animals. These results provide direct evidence that the normal structure of specific plasma membrane regions is perturbed in podocytes that have lost their characteristic array of foot processes and support a role for these domains in the maintenance of normal podocyte architecture.

Animals↗
PubMed1994

GLEPP1, a renal glomerular epithelial cell (podocyte) membrane protein-tyrosine phosphatase. Identification, molecular cloning, and characterization in rabbit.

Podocytes are specialized epithelial cells with delicate interdigitating foot processes which cover the exterior basement membrane surface of the glomerular capillary. They are in part responsible for the extraordinary charge and size filtration characteristics of the glomerulus. To better understand disease processes affecting the glomerular filter, we searched for proteins with relative specificity to the podocyte using a monoclonal antibody strategy. The first such protein characterized (designated glomerular epithelial protein 1 (GLEPP1)) is a membrane protein-tyrosine phosphatase (PTPase) with a large extracellular domain containing eight fibronectin type III-like repeats, a hydrophobic transmembrane segment, and a single PTPase domain. The GLEPP1 PTPase domain shows homology with two other single domain transmembrane PTPases (PTP beta and Drosophila central nervous system PTP10D). This homology includes 2 cysteines in the PTPase domain not present in intracellular or tandem domain membrane PTPases. GLEPP1 PTPase protein is distributed to the podocyte foot processes themselves. RNase protection assay shows that GLEPP1 mRNA is also present in brain. By analogy with the CD45 PTPase of T cells, we expect that this receptor might play a role in maintaining foot process structure and/or function by regulating tyrosine phosphorylation of podocyte proteins.

Amino Acid Sequence↗
PubMed1994

Novel 13A antigen is an integral protein of the basolateral membrane of rat glomerular podocytes.

BACKGROUND: We described recently the 13A monoclonal antibody recognizing a 120 kilodalton protein located at the bases of podocyte foot processes in rat glomeruli. The antigen was extracellular, either a component of the glomerular basement membrane or an integral membrane protein. As only few markers exist for the basal domain of the podocyte membranes, we wanted to characterize the antigen further. EXPERIMENTAL DESIGN: The distribution of the 13A antigen in rat tissues and cultured cells was studied by immunofluorescence and immunoelectron microscopy. Cultured cells were also used for its biochemical and functional characterization. RESULTS: The antigen was detected in several rat epithelial and smooth muscle tissues. In polarized epithelia, it was restricted to the basolateral membranes, and in stratified epithelia, to the basal cell layer. In contrast to its limited distribution in vivo, the antigen was detected in vitro in several cultured fibroblastoid or epithelial rat cell lines, and in cultured mesangial cells. In nonpolarized cells, it had a diffuse granular distribution at the cell surface, and at the ventral surface, it colocalized with vinculin in areas resembling focal adhesions, as shown by double immunofluorescence staining. In polarized epithelial cells, the 13A antigen was concentrated at the basolateral membranes. By immunoelectron microscopy, it was often present at the tips of cell extensions and at adhesion sites. Pretreatment of cryostat sections or cultured cells with trypsin partially inhibited antibody binding, whereas detergents abolished it totally. The antigen of cultured cells could not be identified by Western blotting or immunoprecipitation techniques. The antibodies did not seem to affect cell growth or adhesion. CONCLUSIONS: The 13A antigen is an integral membrane protein of several rat epithelial tissues and cultured cells, and is particularly abundant in the podocyte foot processes. Although its identity and function remain unknown, the 13A protein is a valuable marker for the basal membrane domain of the podocyte.

Animals↗
PubMed1993

The role of novel 30-kD protein in human podocytes: special relevance to proteinuria in glomerulonephritis.

A new monoclonal antibody (MAb) was raised against human glomerular components to investigate the possible existence of glomerular antigens reflecting cellular adaptation in glomerulonephritis. The MAb recognized a podocyte antigen as well as those expressed on renal arterial endothelial cells and smooth muscle cells by indirect immunofluorescence. An additional, but weaker immunoreaction was found in epithelial cells of the Bowman's capsule. This MAb recognized a 30-kD protein on western blotting of glomerular extracts under non-reducing and reducing conditions. Immunoperoxidase electron microscopy revealed that this antigen is present within the cytoplasm, but not on the cell membrane of the podocytes. Moreover, the antigen was found to be reduced in the glomeruli of patients with minimal change glomerulonephritis. These results suggest that the 30-kD protein is a novel protein, which we hypothesize is involved in maintenance of the structural and functional integrity of the podocytes. In addition, reduced expression of the 30-kD protein in the podocytes may be related to the increasing proteinuria in minimal change glomerulonephritis.

Epithelium↗
PubMed1997

Podocyte detachment and epithelial cell reaction in focal segmental glomerulosclerosis with cellular variants.

In primary focal segmental glomerulosclerosis with cellular variants the type of epithelial cells that segmentally or globally increased and their relation to sites where podocytes detached from the capillary wall, remain unclear. Two renal samples containing glomeruli with cellular variants were serially examined using transmission electron microscopy. A total of 10 lesions, including 2 collapsing glomerulopathy, 7 cellular lesions, and 1 sclerosis, were examined. Disappearance of the dense basal band of microfilaments from portions of podocytes was followed by detachment from the capillary basement membrane, resulting in segmental denudation of the capillary wall. The defects were not covered by other portions of epithelial cells, when the defects occurred in more central regions of the glomerulus. When detachment of podocytes occurred in the peripheral areas of the glomerulus, the defects were covered with new basement membrane and by other epithelial cells. These epithelial cells were characterized by the formation of intercellular junctional complexes of zonula adherens and desmosomes between each other and with the parietal epithelial cells (PECs), by showing occasional cilia, apoptotic nuclei, and mitosis. Thus, repair is achieved as the defect is covered by the participation of PECs; synechia and glomerular sclerosis result, depending upon the extent of the original podocyte injury.

Apoptosis↗
PubMed1998

Is vacuolization of podocytes and glomerular endothelial cells of prognostic value with respect to FSGS?

Focal segmental glomerulosclerosis (FSGS) poses a major problem both from the clinical and pathomorphological viewpoint. The diagnosis of FSGS in its early stage is vital mainly because of rapidly developing therapeutic modalities. In the literature various changes are discussed which may be of prognostic value (may predict the development of FSGS). One the these changes in vacuolization, mainly of podocytes and less frequently of endothelial cells. The purpose of the present study was to analyse biopsy specimens to find out to what extent vacuolization of podocytes and endothelial cells is associated with FSGS. We compared vacuolization in minimal change disease (MCD), mesangial glomerulonephritis (GNMES) and FSGS. A similar analysis was made also with respect to those cases of MCD and GNMES, in which electron microscopy suggested an early stage of FSGS. In each group electron micrographs obtained from 15 children were analysed. Electron micrographs (12-15 on average) were obtained most frequently from 3 glomeruli. Each case electron micrographs contained 90-100 podocytes. Based upon the same electron micrographs we counted capillary lumina and defined the percentage of those which contained vacuolized endothelia (we counted the capillary lumina, and not the cells, because it is most frequently impossible to identify the border of vacuolized endothelial cells). The number of capillary cross-sections was 60 on average. The results of the analysis were compared with the clinical data. This comparison did not confirm the hypothesis of other investigators that vacuolization is of a prognostic value. Additionally we evaluated the character of vacuoles. Within podocytes the vacuoles were varying in shape. Surrounded by a single membranous layer most frequently they contained material corresponding to proteins or proteoglycans, rarely to lipids. Sometimes the vacuoles were autophagosomal, occasionally they consisted of the dilated rough endoplasmic reticulum. Vacuole-like changes within the capillary lumina were related to the swelling of endothelial cytoplasm or mesangial processes. The reasons for a discrepancy between our results and those reported by other investigators necessitate further studies.

Child↗