scholarly journals Update on Recurrent Focal Segmental Glomerulosclerosis in Kidney Transplantation

Nephron ◽  
2020 ◽  
pp. 1-6
Author(s):  
Jun Shoji ◽  
Akiko Mii ◽  
Mika Terasaki ◽  
Akira Shimizu
Keyword(s):  
Kidney Transplantation ◽  
Focal Segmental Glomerulosclerosis ◽  
Rapid Progression ◽  
Segmental Glomerulosclerosis ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
History Of ◽  
Stage Renal Disease ◽  
End Stage

<b><i>Background:</i></b> 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. <b><i>Summary:</i></b> 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. <b><i>Key Messages:</i></b> 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.

scholarly journals Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Andreas Kronbichler ◽  
Moin A. Saleem ◽  
Björn Meijers ◽  
Jae Il Shin
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Point Of View ◽  
Soluble Form ◽  
Glomerular Diseases ◽  
Segmental Glomerulosclerosis ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
End Stage

Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerular disorders in both children and adults which can progress to end-stage renal failure. Although there are genetic and secondary causes, circulating factors have also been regarded as an important factor in the pathogenesis of FSGS, because about 40% of the patients with FSGS have recurrence after renal transplantation. Soluble urokinase-type plasminogen activator receptor (suPAR) is a soluble form of uPAR, which is a membrane-bound protein linked to GPI in various immunologically active cells, including podocytes. It has recently been suggested as a potential circulating factor in FSGS by in vitro podocyte experiments, in vivo mice models, and human studies. However, there have also been controversies on this issue, because subsequent studies showed conflicting results. suPAR levels were also increased in patients with other glomerular diseases and were inversely correlated with estimated glomerular filtration rate. Nevertheless, there has been no balanced review on this issue. In this review, we compare the conflicting data on the involvement of suPAR in the pathogenesis of FSGS and shed light on interpretation by taking into account many points and the potential variables and confounders influencing serum suPAR levels.

scholarly journals Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Andreas Kronbichler ◽  
Johannes Leierer ◽  
Jun Oh ◽  
Björn Meijers ◽  
Jae Il Shin
Keyword(s):  
Clinical Practice ◽  
Focal Segmental Glomerulosclerosis ◽  
Transforming Growth Factor ◽  
Disease Onset ◽  
Significant Control ◽  
Segmental Glomerulosclerosis ◽  
History Of ◽  
Small Cohort ◽  
Stage Renal Disease ◽  
End Stage

Focal segmental glomerulosclerosis is a histological pattern on renal biopsy caused by diverse mechanisms. In its primary form, a circulatory factor is implicated in disease onset and recurrence. The natural history of primary FSGS is unpredictable, since some patients are unresponsive towards immunosuppressive measures. Immunologic changes, leading to a proinflammatory or profibrotic milieu, have been implicated in disease progression, namely, glomerular scarring, eventually leading to end-stage renal disease. Among these, interleukin-1ß, tumor-necrosis factor-α(TNF-α), and transforming growth factor-ß1 (TGF-ß1) have emerged as important factors. Translating these findings into clinical practice dampened the enthusiasm, since both TNF-αand TGF-ß1 blockade failed to achieve significant control of the disease. More recently, a role of the complement system has been demonstrated which in fact may be another attractive target in clinical practice. Rituximab, blocking CD20-bearing cells, demonstrated conflicting data regarding efficacy in FSGS. Finally, the T-cell costimulating molecule B7-1 (CD80) is implicated in development of proteinuria in general. Blockade of this target demonstrated significant benefits in a small cohort of resistant patients. Taken together, this review focuses on immunology of FSGS, attributable to either the disease or progression, and discusses novel therapeutic approaches aiming at targeting immunologic factors.

Resveratrol Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis through C3aR/C5aR- Sphingosine Kinase 1 Pathway

Pharmacology ◽  
2017 ◽  
Vol 100 (5-6) ◽  
pp. 253-260 ◽  
Author(s):  
Guoyong Liu ◽  
Qiang Wang ◽  
Yan Shi ◽  
Xiaofei Peng ◽  
Hong Liu ◽  
...  
Keyword(s):  
Body Weight ◽  
Focal Segmental Glomerulosclerosis ◽  
Interstitial Fibrosis ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Segmental Glomerulosclerosis ◽  
Adriamycin Nephropathy ◽  
Type Plasminogen Activator ◽  
Stage Renal Disease ◽  
End Stage

Background/Aim: Focal segmental glomerulosclerosis (FSGS) typically presents with nephrotic range proteinuria, which could eventually develop into end-stage renal disease. Resveratrol (RSV) is a natural polyphenol compound, which has been reported to suppress inflammatory response and renal interstitial fibrosis. This study is aimed at evaluating the renoprotective effect of RSV treatment on adriamycin-induced FSGS. Methods: In Balb/c mice, adriamycin nephropathy was induced by adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then the mice were treated with RSV (40 mg/kg body weight) once daily by oral gavage, again starting on the day of adriamycin injection and continued for 6 weeks. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis. Results: When treated with adriamycin, the expressions of C3aR, C5aR, sphingosine kinase 1 (Sphk1), and soluble urokinase-type plasminogen activator receptor (suPAR) were upregulated, while RSV treatment could inhibit the expressions of C3aR, C5aR, Sphk1, and suPAR, eventually leading to anti-inflammatory and anti-fibrosis conditions. Conclusion: RSV attenuates adriamycin-induced FSGS through C3aR/C5aR-Sphk1 pathway.

scholarly journals Diagnostic and Prognostic Value of Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) in Focal Segmental Glomerulosclerosis and Impact of Detection Method

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wolfgang Winnicki ◽  
Gere Sunder-Plassmann ◽  
Gürkan Sengölge ◽  
Ammon Handisurya ◽  
Harald Herkner ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Focal Segmental Glomerulosclerosis ◽  
Sensitivity And Specificity ◽  
High Sensitivity ◽  
Test Methods ◽  
Segmental Glomerulosclerosis ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Plasminogen Activator Receptor ◽  
Stage Renal Disease

Abstract The plasma soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker for focal segmental glomerulosclerosis (FSGS), but its value is under discussion because of ambiguous results arising from different ELISA methods in previous studies. The aim of this study was to compare diagnostic performance of two leading suPAR ELISA kits and examine four objectives in 146 subjects: (1) plasma suPAR levels according to glomerular disease (primary, secondary and recurrent FSGS after kidney transplantation, other glomerulonephritis) and in healthy controls; (2) suPAR levels based on glomerular filtration rate; (3) sensitivity and specificity of suPAR for FSGS diagnosis and determination of optimal cut-offs; (4) suPAR as prognostic tool. Patients with FSGS showed significant higher suPAR values than patients with other glomerulonephritis and healthy individuals. This applied to subjects with and without chronic kidney disease. Although both suPARnostic™ assay and Quantikine Human uPAR ELISA Kit exerted high sensitivity and specificity for FSGS diagnosis, their cut-off values of 4.644 ng/mL and 2.789 ng/mL were significantly different. Higher suPAR was furthermore predictive for progression to end-stage renal disease. In summary, suPAR values must be interpreted in the context of population and test methods used. Knowing test specific cut-offs makes suPAR a valuable biomarker for FSGS.

scholarly journals Treatment of Focal Segmental Glomerulosclerosis Recurrence in the Renal Allograft: A Report of Two Cases

2016 ◽  
Vol 6 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Minh-Ha Tran ◽  
Cynthia Chan ◽  
Whitney Pasch ◽  
Philip Carpenter ◽  
Hirohito Ichii ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Focal Segmental Glomerulosclerosis ◽  
Renal Allograft ◽  
Therapeutic Plasma Exchange ◽  
Spot Urine ◽  
Segmental Glomerulosclerosis ◽  
Glomerular Lesions ◽  
Stage Renal Disease ◽  
End Stage

Focal segmental glomerulosclerosis (FSGS) causes glomerular lesions that can progress to end-stage renal disease. It is suspected to be caused by a circulating factor that is amenable to plasmapheresis removal and exhibits a risk for recurrence in the renal allograft. We present two patients with FSGS recurrence in their allograft kidneys diagnosed by biopsy after significant proteinuria developed in the posttransplant setting. Treatment with therapeutic plasma exchange induced long-term remission in both patients. Spot urine protein:creatinine ratios were monitored and treatment was continued until a target of <0.5 was achieved. In patient number two, a second peak in proteinuria and azotemia was ultimately attributable to ureteral stenosis and these values normalized following repair. In conclusion, therapeutic plasma exchange is an effective treatment for FSGS recurring following renal transplant.

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.

scholarly journals Laparoscopic-Assisted Recipient Nephrectomy and Recipient Kidney Procurement during Orthotopic Living-Related Kidney Transplantation

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Dimitri Mikhalski ◽  
Karl Martin Wissing ◽  
Renaud Bollens ◽  
Daniel Abramowicz ◽  
Vincent Donckier ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Antiphospholipid Antibodies ◽  
Graft Function ◽  
Renal Vessels ◽  
Short Period ◽  
History Of ◽  
Stage Renal Disease ◽  
End Stage ◽  
Living Related ◽  
Laparoscopic Assisted

Advanced atherosclerosis or thrombosis of iliac vessels can constitute an absolute contraindication for heterotopic kidney transplantation. We report the case of a 42-year-old women with end-stage renal disease due to lupus nephritis and a history of bilateral thrombosis of iliac arteries caused by antiphospholipid antibodies. Occlusion had been treated by the bilateral placement of wall stents which precluded vascular anastomosis. The patient was transplanted with a right kidney procured by laparoscopic nephrectomy from her HLA semi-identical sister. The recipient had left nephrectomy after laparoscopical transperitoneal dissection. The donor kidney was orthotopically transplanted with end-to-end anastomosis of graft vessels to native renal vessels and of the graft and native ureter. Although, the patient received full anticoagulation because of a cardiac valve and antiphospholipid antibodies, she had no postoperative complication in spite of a short period of delayed graft function. Serum creatinine levels three months after transplantation were at 1.0 mg/dl. Our case documents that orthotopical transplantation of laparoscopically procured living donor kidneys at the site of recipient nephrectomy is a feasible procedure in patients with surgical contraindication of standard heterotopic kidney transplantation.

scholarly journals Fetal Renal Echogenicity Associated with Maternal Focal Segmental Glomerulosclerosis: The Effect of Transplacental Transmission of Permeability Factor suPAR

2018 ◽  
Vol 7 (10) ◽  
pp. 324 ◽  
Author(s):  
Shirley Shuster ◽  
Ghada Ankawi ◽  
Christoph Licht ◽  
Jochen Reiser ◽  
Xuexiang Wang ◽  
...  
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Transplacental Transmission ◽  
Transplacental Passage ◽  
Segmental Glomerulosclerosis ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Plasminogen Activator Receptor ◽  
Maternal Fetal Transmission ◽  
Fetal Response ◽  
Echogenic Kidneys

We report a case of a pregnant woman with nephrotic syndrome due to biopsy-proven focal segmental glomerulosclerosis (FSGS) whose fetus developed echogenic kidneys and severe oligohydramnios by 27 weeks of gestation. Maternal treatment with prednisone resulted in normalization of the amniotic fluid indices and resolution of fetal renal echogenicity. The newborn was noted to have transient renal dysfunction and proteinuria, resolving by 6 weeks postpartum. The transplacental passage of permeability factors is postulated to have caused both the fetal and newborn renal presentation, with significantly elevated levels of soluble urokinase-type plasminogen activator receptor (suPAR) noted in the cord blood. This case documents the transplacental maternal-fetal transmission of suPAR, demonstrating the potential for maternal-fetal transmission of deleterious, disease-causing entities, and adds to the differential diagnosis of fetal echogenic kidneys. Further, this is the first documentation of a fetal response to maternal systemic therapy.

Sign in / Sign up

Export Citation Format

Share Document