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 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 Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to Immunosuppression

Kidney360 ◽  
2020 ◽  
pp. 10.34067/KID.0006172020
Author(s):  
Benjamin M. Forster ◽  
Robert Nee ◽  
Dustin J. Little ◽  
Peter J. Greasley ◽  
James B. Hughes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kidney Disease ◽  
Focal Segmental Glomerulosclerosis ◽  
Renal Survival ◽  
End Stage Kidney Disease ◽  
Interstitial Inflammation ◽  
Segmental Glomerulosclerosis ◽  
End Stage

Background: Focal segmental glomerulosclerosis (FSGS) is a heterogeneic glomerular disease. Risk factors for end- stage kidney disease (ESKD) and impact of immunosuppression treatment (IST) has varied in previously published cohorts. These cohorts were limited by relatively small case numbers, short follow up, lack of racial/ethnic diversity, a mix of adult and pediatric patients, lack of RAAS inhibition, or lack of subgroup analysis of IST. Methods: We compared demographics, clinical characteristics, histopathology and IST to long term renal survival in a large, ethnically diverse, adult cohort of 338 biopsy-proven FSGS cases with long term follow up in the era of RAAS inhibition using data from the United States Department of Defense health care network. Results: Multivariate analysis showed that nephrotic range proteinuria (NRP), estimated glomerular filtration rate <60 ml/min/1.73m2, hypoalbuminemia, interstitial fibrosis and tubular atrophy, and interstitial inflammation at diagnosis as well as the absence of remission were all associated with worse long term renal survival. IgM, C3, and a combination of IgM/C3 immunofluorescence staining were not associated with reduced renal survival. IST was not associated with improved renal survival in the whole cohort, or in a subgroup with NRP. However, IST was associated with better renal survival in a subgroup of FSGS cases with both NRP and hypoalbuminemia and hypoalbuminemia alone. Conclusion: Our study suggests that IST should be reserved for FSGS patients with nephrotic syndrome. It also introduces interstitial inflammation as a potential risk factor for ESKD and does not support the proposed pathogenicity of IgM and complement activation.

Long-term plasmapheresis therapy in the management of focal segmental glomerulosclerosis recurrence after kidney transplantation

2021 ◽  
pp. 103046
Author(s):  
Gonzalo Ramirez-Guerrero ◽  
Angel M Sevillano Prieto ◽  
Fernando Jara-Vilugrón ◽  
Natalia Polanco Fernandez ◽  
Esther Gonzalez Monte ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Focal Segmental Glomerulosclerosis ◽  
Segmental Glomerulosclerosis

scholarly journals Long-term outcome of kidney transplantation in adult recipients with focal segmental glomerulosclerosis

2001 ◽  
Vol 42 (2) ◽  
pp. 209 ◽  
Author(s):  
Kyu Hun Choi ◽  
Soon Il Kim ◽  
Soo Young Yoon ◽  
Jae Hun Kim ◽  
Shin Wook Kang ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Focal Segmental Glomerulosclerosis ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Segmental Glomerulosclerosis

scholarly journals The use of belatacept in kidney transplantation

2018 ◽  
Vol 10 (3) ◽  
pp. 222-231
Author(s):  
N. N. Babenko ◽  
V. A. Goryainov ◽  
M. M. Kaabak ◽  
V. V. Nikoda ◽  
E. A. Lishova
Keyword(s):  
Kidney Transplantation ◽  
Calcineurin Inhibitors ◽  
Research Centre ◽  
Kidney Transplant Recipients ◽  
Long Term Outcomes ◽  
Maintenance Immunosuppression ◽  
Improve Compliance ◽  
One Year

Background. Kidney transplantation efficacy is limited by immunosuppression nephrotoxicity, antibody-mediated and chronic rejection. Avoiding immunosuppression nephrotoxicity is a promising strategy to improve long term outcomes. Belatacept, a synthetic immunoglobulin which blocks CD28-B7 pathway of T-lymphocyte costimulation, is considered as an alternative to calcineurin inhibitors in maintenance immunosuppression since it has no nephrotoxicity. Purpose: to evaluate belatacept efficacy and safety for maintenance immunosuppression therapy after kidney transplantatin based on the clinical experience.Material and methods. From March 2017 to May 2018, we used belatacept in five kidney transplant recipients (one female and four males aged from 4 to 21 years) in the Kidney Transplantation Department of Petrovsky National Research Centre of Surgery Three kidneys were taken from related living donors, two kidney grafts were from deceased donors. Conversion from CNI to belatacept was performed between 6 and 112 month after transplantation. Patients were followed-up for average 12 months after conversion. We have described here these five cases, providing individual indications and the outcome of conversion.Results. The conversion failed in two children switched to belatacept with the purpose to improve compliance. Three patients switched to belatacept because of tacrolimus toxicity demonstrated good results in one year follow up.Conclusion. Belatacept demonstrated good results if was used instead of calcineurin inhibitors when the latter were poorly tolerated. The use of belatacept in multidrug immunosuppression in noncompliant patients was ineffective.

Immunoadsorption for Recurrent Primary Focal Segmental Glomerulosclerosis on Kidney Allografts: A Single-Center Experience and Literature Review

2020 ◽  
Vol 49 (3) ◽  
pp. 322-333 ◽  
Author(s):  
Hamza Naciri Bennani ◽  
Juste Yérémandé Bonzi ◽  
Johan Noble ◽  
Florian Terrec ◽  
Lionel Motte ◽  
...  
Keyword(s):  
Primary Objective ◽  
Allograft Survival ◽  
Frequent Adverse Event ◽  
Single Center Experience ◽  
Cytomegalovirus Reactivation ◽  
Segmental Glomerulosclerosis ◽  
The Mean ◽  
Allograft Loss

Introduction: Primary focal and segmental glomerulosclerosis (FSGS) frequently reoccurs on kidney transplants and may lead to premature allograft loss. There are no guidelines for treating FSGS recurrence on allografts; treatment is based on apheresis (plasma exchange plasmapheresis [PP], semi-specific immunoadsorption [IA] with reusable columns) plus rituximab. Objective: We aimed to assess the efficacy of IA to treat recurrent FSGS. Methods: We report on 7 patients with recurrent FSGS on kidney allograft (proteinuria ≥3 g/g of urinary creatinine or ≥3 g/day); they all received IA. Our primary objective was to reduce proteinuria by >50%. Patients’ mean age was 45 ± 10 years. Postoperative immunosuppression relied on steroids, mycophenolate mofetil, tacrolimus, with an induction therapy of basiliximab or antithymocyte globulins. Prophylaxis to prevent FSGS recurrence was either rituximab alone (n = 3), rituximab plus either PP or IA (n = 3), or no treatment (n = 1). Mean follow-up was 20 ± 13 months. There was a median of 72 (14–101) IA sessions per patient, that is, a mean of 14 ± 1 sessions per IA column. Results: At 12 months after starting IA, all patients had partial (n = 6) or complete (n = 1) remission, and allograft survival was 100%. The mean reduction in proteinuria within an IA session was 45 ± 15%. At last follow-up, 2 patients are in remission without IA, 3 patients are in partial remission that is IA dependent, and 2 patients lost their allograft due to FSGS recurrence. The most frequent adverse event was cytomegalovirus reactivation (n = 13), which subsided after valganciclovir therapy. Conclusions: We show that recurrence of FSGS can be controlled long term with IA plus rituximab. However, some patients remained dependent on IA.

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