Expression of Cell Membrane Antigens in Cells Excreted in the Urinary Sediment Predicts Progression of Renal Disease in Patients with Focal Segmental Glomerulosclerosis

2015 ◽  
Vol 42 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Andrzej Konieczny ◽  
Agnieszka Czyżewska-Buczyńska ◽  
Monika Ryba ◽  
Dagna Rukasz ◽  
Magdalena Krajewska ◽  
...  
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Prognostic Significance ◽  
Double Staining ◽  
Urinary Sediment ◽  
Cell Numbers ◽  
Segmental Glomerulosclerosis ◽  
Membrane Antigens ◽  
Cell Membrane Antigens ◽  
Parietal Epithelial Cells

Background/Aims: A link between the number of podocytes excreted in the urine and activity of glomerular disease has been established. The aim of this study was to investigate possible correlations between urinary cells' phenotype and the progression of focal segmental glomerulosclerosis (FSGS). Methods: Forty patients with newly diagnosed FSGS were included. Cells were isolated from urine by adherence to collagen-coated cover slips and assessed for the expression of podocalyxin (PDX), CD68 and Ki67 antigens by indirect immunofluorescence. In addition, double-staining procedures were performed in combinations of the above antigens plus cytokeratin, WT1 and CD-105. Twenty-two patients in whom urinary protein to creatinine ratio exceeded 2.0 at diagnosis were followed for 36 months, with assessments of renal function and proteinuria every 3 months. During observation, patients were subjected to standard therapy. Results: Significantly higher numbers of Ki67 positive cells at the onset of the study were observed in patients who have doubled serum creatinine (SCr) in follow-up, than in those who have not (p = 0.0149). By logistic regression analysis, both CD68 and Ki67, but not anti-PDX positive cell numbers at diagnosis were found to be predictors of doubling SCr concentration in 36 months' follow-up. Results of double staining indicate that PDX positive cells could be identified as podocytes or their precursors and parietal epithelial cells. Conclusion: Urinary sediment PDX positive cell numbers do not predict the progression of FSGS, whereas CD68 and Ki67 phenotype of urinary podocytic lineage clearly has a prognostic significance in 36 months' observation of primary FSGS.

scholarly journals Successful long-term management of recurrent focal segmental glomerulosclerosis after kidney transplantation with costimulation blockade

2020 ◽  
Author(s):  
Thomas Mühlbacher ◽  
Kerstin Amann ◽  
Moritz Mahling ◽  
Silvio Nadalin ◽  
Nils Heyne ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Focal Segmental Glomerulosclerosis ◽  
Costimulation Blockade ◽  
Segmental Glomerulosclerosis ◽  
Remission Maintenance ◽  
Maintenance Immunosuppression ◽  
Therapeutic Concepts ◽  
Allograft Outcome

Abstract Recurrence of primary focal segmental glomerulosclerosis (FSGS) occurs in up to 50% of patients after kidney transplantation and is associated with poor allograft outcome. Novel therapeutic concepts directly target podocyte function via B7-1 with inconsistent response. We present the case of a 19 yr. old patient with recurrent primary FSGS early after living donor kidney transplantation. Plasmapheresis and rituximab did not induce remission. Repetitive abatacept administration was able to achieve partial remission. Maintenance immunosuppression was subsequently switched to a belatacept-based CNI-free immunosuppression, resulting in sustained complete remission with excellent allograft function throughout a follow-up of more than 56 months.

MO294COMPARISON OF TIP AND CELLULAR VARIANT OF PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Nikola Zagorec ◽  
Ivica Horvatić ◽  
Dino Kasumović ◽  
Petar Šenjug ◽  
Matija Horaček ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Clinical Features ◽  
Remission Rate ◽  
Prognostic Significance ◽  
European Population ◽  
University Hospital ◽  
Outcome Analysis ◽  
Laboratory Findings ◽  
Segmental Glomerulosclerosis

Abstract Background and Aims After membranous nephropathy, focal segmental glomerulosclerosis (FSGS) is the most common cause of nephrotic syndrome in European population. According to Columbia classification, there are five histological variants of FSGS defined on light microscopy (tip, cellular, perihilar, collapsing and not otherwise specified - NOS) and this classification has a prognostic significance. The aim is to compare features and outcomes of tip and cellular variant of primary FSGS. Method All patients with FSGS were identified by a retrospective review of the Registry of kidney biopsies at the Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb, from 2003 until 2020. Each kidney specimen was analyzed by light, immunofluorescent and electron microscopy and Columbia classification was applied by experienced nephropathologist. Patients with primary FSGS met following criteria: full nephrotic syndrome and diffuse podocyte foot process effacement in absence of secondary causes of FSGS. Laboratory findings were obtained for every patient at the time of biopsy and following outpatient visits. Complete remission was defined as proteinuria < 0.3 g/day with normal kidney function and partial remission as proteinuria 0.3 - 3.5 g/day. Variables are expressed as median ± IQR (interquartile range) and frequencies. Statistical comparison between groups of patients with tip and cellular variant of primary FSGS and disease outcome analysis were done. Results Out of 200 patients with FSGS, 59 (29.5 %) had primary form of disease. Tip variant was the most common form of primary FSGS (22 patients, 37 %) followed by NOS (20, 34 %), cellular (13, 22 %), perihilar (2, 3.5 %) and collapsing (2, 3.5 %) variant. Demographic and clinical features with initial laboratory findings are shown in Table 1. There were no significant differences between two groups in all analyzed variables in Figure 1. All patients were treated by anti-RAAS agents and steroids. Median follow-up was 55 months (range 1 – 196 months), and followup data were unavailable for three patients. Figure 2 shows treatment regimens in both patient grouos with treatment outcomes. Remission rate was significantly higher in tip variant (90 % vs. 41 %, p = 0.002). There was no difference in relapse rate between the two groups (p = 0.717). Conclusion There were no significant differences in clinical features and laboratory findings at the time of clinical presentation between tip and cellular variant of primary FSGS. Patients with tip variant had significantly higher remission rate than patients with cellular variant.

scholarly journals P0372RITUXIMAB IN IDIOPATHIC FOCAL SEGMENTAL GLOMERULOSCLEROSIS OF THE ADULT: A MULTICENTRE RETROSPECTIVE SURVEY OF 31 PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Martina Tedesco ◽  
Isabella Pisani ◽  
Marco Allinovi ◽  
Giovanni Casazza ◽  
Lucia Del Vecchio ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Focal Segmental Glomerulosclerosis ◽  
Immunosuppressive Treatment ◽  
Case Series ◽  
Post Transplantation ◽  
Steroid Resistant ◽  
Segmental Glomerulosclerosis ◽  
Steroid Dependent ◽  
Stage Renal Disease

Abstract Background and Aims Idiopathic Focal Segmental Glomerulosclerosis (FSGS) is a rare glomerulonephritis often complicated by a chronic relapsing course frequently characterized by dependency or resistance to immunosuppressive treatment. Moreover, about half of the patients with active disease would develop end-stage renal disease within 10 years from the diagnosis, highlighting the need of novel therapeutic approaches. Rituximab (RTX), a chimeric monoclonal antibody against CD20, showed promising results in pediatric steroid-dependent/frequently relapsing FSGS and in post-transplantation recurrence. However, evidence about its role in the FSGS of the adult is still lacking with small case series suggesting conflicting results. In this study we assess the efficacy of RTX in the largest cohort of adults with FSGS currently available in literature. Methods Adults with biopsy proven idiopathic FSGS treated with RTX were retrospectively identified among several Italian nephrology units. Response to RTX was evaluated at 3, 6, 12 months and, when available, during the long-term follow-up. A positive response (POR) was defined as: (1) proteinuria <3.5 g/die with a decrease >50% compared to baseline, (2) stable renal function (3) decreased or stable dose of glucocorticoids and other immunosuppressants. Severe Adverse Events (SAEs) have been recorded. Results 31 patients have been identified: 18 steroid-dependent, 11 steroid-resistant, and 2 patients with major contraindication to steroid therapy. RTX has been administered at a median of 87 months (IQR 54–96) from the diagnoses using heterogeneous schedules of administration. Overall, the POR rate at 6 months was 52% (steroid-dependent=69%; steroid-resistant=22%). At univariate analyses, POR to RTX at 6 months was associated to the steroid-dependent status (p=0.0347) and a proteinuria at RTX <5 g/die (p=0.0173); a trend towards better response was observed in patients with IgG at RTX <500 mg/dl (p=0.0774). Over the first year of follow-up, the proteinuria and serum albumin significantly improved (respectively, p=0.0021 and p=0.0277 at 12 months), while serum creatinine remained stable (figure). Among treated patients, the median dose of prednisone decreased from 15 mg/die (IQR 12.5–25) at baseline to 10 mg/die (IQR 5–15) at 12 months, while the proportion of patients free from glucocorticoids respectively increased from 42% to 54%. Six patients have been retreated within a year since the first RTX: of these only the 2 patients who have experienced a POR to the first administration obtained a further POR after retreatment. After the 12th month, 11 patients have been followed for a median time of 17 months (IQR 15–33.5): of the 5/11 with a POR at the 12th month, 2/5 maintained a POR without needing further immunosuppression, 2/5 maintained a POR with a pre-emptive RTX based maintenance treatment, 1/5 experienced a relapse successfully managed with RTX needing then a pre-emptive RTX based maintenance therapy able to allow a persistent POR. Overall, 9 SAEs have been recorded with requirement of hospital admission for clinical deterioration being the most frequent. Conclusion RTX may be an option in the FSGS of the adult, especially in the steroid-dependent patients and the ones with less severe nephrotic syndrome. In the responders, a RTX based maintenance therapy may be required.

Up-Regulation of CD74 Expression in Parietal Epithelial Cells in a Mouse Model of Focal Segmental Glomerulosclerosis

Nephron ◽  
2016 ◽  
Vol 134 (4) ◽  
pp. 238-252 ◽  
Author(s):  
Takeshi Yamazaki ◽  
Satoshi Sasaki ◽  
Takayuki Okamoto ◽  
Yasuyuki Sato ◽  
Asako Hayashi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Focal Segmental Glomerulosclerosis ◽  
Segmental Glomerulosclerosis ◽  
Parietal Epithelial Cells

scholarly journals Parietal epithelial cells maintain the epithelial cell continuum forming Bowman's space in focal segmental glomerulosclerosis

2021 ◽  
Author(s):  
Laura Miesen ◽  
Péter Bándi ◽  
Brigith Willemsen ◽  
Fieke Mooren ◽  
Thiago Strieder ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Focal Segmental Glomerulosclerosis ◽  
Glomerular Epithelial Cell ◽  
Segmental Glomerulosclerosis ◽  
Glomerular Epithelial Cells ◽  
Tubular System ◽  
Sclerotic Lesions ◽  
Parietal Epithelial Cells ◽  
Glomerular Tuft

In the glomerulus, Bowman's space is formed by a continuum of glomerular epithelial cells. In focal segmental glomerulosclerosis (FSGS), glomeruli show segmental scarring, a result of activated PECs invading the glomerular tuft. The segmental scars interrupt the epithelial continuum. However, non-sclerotic segments seem to be preserved even in glomeruli with advanced lesions. We studied the histology of the segmental pattern in Munich Wistar Frömter (MWF) rats, a model for secondary FSGS. Our results showed that matrix layers lined with PECs cover the sclerotic lesions. These PECs formed contacts with podocytes of the uninvolved tuft segments, restoring the epithelial continuum. Formed Bowman's spaces were still connected to the tubular system. Furthermore, in biopsies of patients with secondary FSGS we also detected matrix layers formed by PECs, separating the uninvolved from the sclerotic glomerular segments. While PECs have a major role in the formation of glomerulosclerosis, we showed that in FSGS, PECs also restore the glomerular epithelial cell continuum that surrounds Bowman's space. This process may be beneficial and indispensable for glomerular filtration in the uninvolved segments of sclerotic glomeruli.

scholarly journals Pediatric Focal Segmental Glomerulosclerosis: Favorable Transplantation Outcome With Plasma Exchange

2021 ◽  
Author(s):  
Fatina I Fadel ◽  
Hafez M Bazaraa ◽  
Mohamed A Abdel Mawla ◽  
Doaa M Salah
Keyword(s):  
Plasma Exchange ◽  
Focal Segmental Glomerulosclerosis ◽  
Survival Data ◽  
Early Recurrence ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Segmental Glomerulosclerosis ◽  
Kaplan Meier ◽  
One Year

Abstract Background: Although kidney transplantation (KT) is the treatment of choice for pediatric kidney failure (KF); concerns for recurrence in cases of focal segmental glomerulosclerosis (FSGS) are still present. This study aimed to investigate the outcome of KT in children with KF secondary to FSGS, with implementation of preemptive perioperative plasma exchange (PE) for non-genetically proven patients.Methods: Forty FSGS pediatric kidney transplant recipients were studied. Of them: 12 patients (30%) had genetically proven NPHS2 mutations/familial and 28 (70%) were sporadic FSGS patients. Sporadic patients electively received 6 preoperative PE sessions. Recurrence of proteinuria was managed with PE and Rituximab (RTX). Kaplan-Meier curves were used to analyze graft and recurrence free survival data.Results: The mean follow-up duration after KT was 3.8 ± 2.86 years. Recurrence of proteinuria was encountered early postoperative in 11 patients (27.5%) and late (1.6 and 2.9 years after KT) in 2 patients (5%). Proteinuria was less in patients underwent native nephrectomy than others immediately postoperative and at assessment (p= 0.002 & 0.0031 respectively). One-year graft and patient survival was 93.8% with a mean 1-year serum creatinine of 0.67 ± 0.25 mg/dl. Three graft losses (7.5%) were due to chronic rejection 3.3, 3.75 and 4.17 years after KT and 2 patients' mortality (5%) occurred early postoperative (first 2 weeks) due to infection.Conclusion: FSGS transplanted children have favorable outcomes with perioperative PE for non-genetically proven cases. Early recurrence after KT can be successfully managed with PE and RTX.

scholarly journals Efficacy and safety of rituximab in adult frequent-relapsing or steroid-dependent minimal change disease or focal segmental glomerulosclerosis: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Cheng Xue ◽  
Bo Yang ◽  
Jing Xu ◽  
Chenchen Zhou ◽  
Liming Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Focal Segmental Glomerulosclerosis ◽  
Minimal Change Disease ◽  
Meta Analysis ◽  
Minimal Change ◽  
Efficacy And Safety ◽  
Segmental Glomerulosclerosis ◽  
Steroid Dependent

Abstract Background The efficacy and safety of rituximab (RTX) in adult frequent-relapsing (FR) or steroid-dependent (SD) nephrotic syndrome (NS), including minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS), are still inconclusive. Methods We performed a systematic review and meta-analysis registered in  PROSPERO (CRD42019148102) by pooling data of cohort studies or case series on adult patients with difficult-to-treat NS. Steroid-resistant NS was excluded. The primary outcomes were the complete remission (CR) rate and the relapse rate. Partial remission (PR) rate, no response (NR) rate and adverse events were the secondary outcomes. A random-effects model was performed for all the outcomes. Results We included 21 studies involving 382 adult MCD/FSGS subjects with a median follow-up duration from 12 to 43 months. RTX treatment induced a pooled 84.2% CR rate [95% confidence interval (CI): 67.7–96.3%], while MCD patients had a high 91.6% CR rate and FSGS patients a moderate 43% CR rate. However, 27.4% (95% CI 20.7–34.5%) of the patients relapsed during the follow-up. The pooled PR and NR rates were 5.8% (95% CI 1.2–12.5%) and 5.2% (95% CI 0.0–15.0%), respectively. RTX was associated with trivial adverse events and good tolerance. Conclusions In summary, by pooling results of current pilot studies, RTX may be an effective and relatively safe alternative for most adult FR or SD MCD/FSGS to displace calcineurin inhibitors or prednisone in the hierarchy of treatment. More clinical trials comparing RTX with other immunosuppressants and concerning the long-term adverse events are needed.

Focal segmental glomerulosclerosis histologic variants and renal outcomes based on nephrotic syndrome, immunosuppression, and proteinuria remission

2021 ◽  
Author(s):  
Takehiko Kawaguchi ◽  
Toshiyuki Imasawa ◽  
Moritoshi Kadomura ◽  
Hiroshi Kitamura ◽  
Shoichi Maruyama ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Renal Outcome ◽  
Renal Outcomes ◽  
Not Otherwise Specified ◽  
Segmental Glomerulosclerosis ◽  
Subgroup Analyses ◽  
Renal Prognosis ◽  
End Stage

Abstract Background The associations of focal segmental glomerulosclerosis (FSGS) histologic variants with renal outcomes have rarely been investigated comprehensively by clinically relevant subgroups in this modern age. Methods Data on 304 (173 nephrotic and 131 non-nephrotic) patients with biopsy-confirmed FSGS from 2010 to 2013 were analyzed using the Japanese nationwide renal biopsy registry. The primary outcome was a composite of a 30% decline in estimated glomerular filtration rate or progression to end stage kidney disease 5 years from the biopsy. We compared outcomes of FSGS variants according to the Columbia classification using survival analyses. Subgroup analyses were performed based on nephrotic syndrome (NS), immunosuppression, and proteinuria remission (PR, proteinuria <0.3 g/day) during follow-up. Additionally, associations of NS, immunosuppression, and PR with outcomes were examined for each variant. Results The distribution of variants was 48% (n = 145) FSGS not otherwise specified (NOS), 19% (n = 57) tip, 15% (n = 47) perihilar, 13% (n = 40) cellular, and 5% (n = 15) collapsing. The outcome event occurred in 87 patients (29%). No significant differences in the outcome were found among the variants. Subgroup analyses yielded similar results. However, there was a trend toward improved outcome in patients with PR irrespective of variants (hazard ratio adjusted for histologic variant and potential confounders [adjusted HR]: 0.19 [95% confidence interval (CI), 0.10–0.34]). NS was marginally associated with better outcome compared with non-NS (adjusted HR: 0.50 [95% CI, 0.25–1.01]. Conclusions FSGS variants alone might not have significant impacts on the renal outcome after 5 years, while PR could be predictive of improved renal prognosis for any variant. Specific strategies and interventions to achieve PR for each variant should be implemented for better renal outcomes.

Is CD44 in glomerular parietal epithelial cells a pathological marker of renal function deterioration in primary focal segmental glomerulosclerosis?

2017 ◽  
Vol 32 (11) ◽  
pp. 2165-2169 ◽  
Author(s):  
Brunna Pinto Froes ◽  
Stanley de Almeida Araújo ◽  
Eduardo Alves Bambirra ◽  
Eduardo Araújo Oliveira ◽  
Ana Cristina Simões e Silva ◽  
...  
Keyword(s):  
Renal Function ◽  
Epithelial Cells ◽  
Focal Segmental Glomerulosclerosis ◽  
Segmental Glomerulosclerosis ◽  
Renal Function Deterioration ◽  
Parietal Epithelial Cells
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