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Raina R, Jothi S, Haffner D, Somers M, Filler G, Vasistha P, Chakraborty R, Shapiro R, Randhawa PS, Parekh R, Licht C, Bunchman T, Sethi S, Mangat G, Zaritsky J, Schaefer F, Warady B, Bartosh S, McCulloch M, Alhasan K, Swiatecka-Urban A, Smoyer WE, Chandraker A, Yap HK, Jha V, Bagga A, Radhakrishnan J. Post-transplant recurrence of focal segmental glomerular sclerosis: consensus statements. Kidney Int 2024; 105:450-463. [PMID: 38142038 DOI: 10.1016/j.kint.2023.10.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 10/03/2023] [Accepted: 10/17/2023] [Indexed: 12/25/2023]
Abstract
Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review.
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Affiliation(s)
- Rupesh Raina
- Department of Nephrology, Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, Ohio, USA; Department of Nephrology, Akron Children's Hospital, Akron, Ohio, USA
| | - Swathi Jothi
- Department of Nephrology, Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, Ohio, USA
| | - Dieter Haffner
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
| | - Michael Somers
- Division of Nephrology, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Guido Filler
- Department of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
| | - Prabhav Vasistha
- Department of Nephrology, Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, Ohio, USA
| | - Ronith Chakraborty
- Department of Nephrology, Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, Ohio, USA; Department of Nephrology, Akron Children's Hospital, Akron, Ohio, USA
| | - Ron Shapiro
- Recanati/Miller Transplantation Institute, The Mount Sinai Medical Center, New York, New York, USA
| | - Parmjeet S Randhawa
- Department of Pathology, Thomas E Starzl Transplant Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Rulan Parekh
- Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
| | - Christopher Licht
- Division of Pediatric Nephrology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Timothy Bunchman
- Pediatric Nephrology and Transplantation, Children's Hospital of Richmond at Virginia Commonwealth University (VCU), Richmond, Virginia, USA
| | - Sidharth Sethi
- Pediatric Nephrology, Kidney Institute, Medanta, The Medicity Hospital, Gurgaon, Haryana, India
| | - Guneive Mangat
- Department of Nephrology, Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, Ohio, USA
| | - Joshua Zaritsky
- Division of Pediatric Nephrology, Nemours, A.I. duPont Hospital for Children, Wilmington, Delaware, USA
| | - Franz Schaefer
- Department of Pediatric Nephrology, University Children's Hospital Heidelberg, Heidelberg, Germany
| | - Bradley Warady
- Division of Nephrology, University of Missouri-Kansas City School of Medicine, Children's Mercy, Kansas City, Missouri, USA
| | - Sharon Bartosh
- Department of Pediatrics, University of Wisconsin Medical School, Madison, Wisconsin, USA
| | - Mignon McCulloch
- Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa
| | - Khalid Alhasan
- Nephrology Unit, Pediatrics Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Pediatric Kidney Transplant Division, Organ Transplant Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Agnieszka Swiatecka-Urban
- University of Virginia Children's Hospital, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - William E Smoyer
- Center for Clinical and Translational Research and Division of Nephrology, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio, USA
| | - Anil Chandraker
- Transplantation Research Center, Kidney and Pancreas Transplantation, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Hui Kim Yap
- Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, Singapore, Singapore
| | - Vivekanand Jha
- George Institute for Global Health, University of New South Wales (UNSW), New Delhi, India; School of Public Health, Imperial College, London, UK; Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, India
| | - Arvind Bagga
- Division of Pediatric Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - Jai Radhakrishnan
- Department of Medicine (Nephrology), Columbia University Medical Center, New York, New York, USA.
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Ahmad SB, Peleg Y, Ahn W. Current approaches to overcome recurrent focal segmental glomerulosclerosis after kidney transplantation. Curr Opin Nephrol Hypertens 2024; 33:61-66. [PMID: 37921337 DOI: 10.1097/mnh.0000000000000946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2023]
Abstract
PURPOSE OF REVIEW Recurrent focal segmental glomerulosclerosis (FSGS) presents with nephrotic syndrome shortly after kidney transplantation. This review will overview the role of circulating permeability factors in disease pathogenesis and treatment options for recurrent FSGS. RECENT FINDINGS Novel circulating permeability factors have been identified in serum samples. Current research is focused on detection of permeability factors as a marker of treatment response. Furthermore, novel monoclonal antibodies are being utilized to further induce remission. SUMMARY Posttransplant recurrent FSGS can have a deleterious effect on allograft. Early detection of disease recurrence with prompt treatment is optimal for clinical remission. Plasmapheresis with anti-B cell therapy is considered the mainstay of treatment. Newer B cell therapies and detection of circulating factors in serum may help in providing targeted treatment in a subset of patients.
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Affiliation(s)
- Syeda Behjat Ahmad
- University of Pittsburgh School of Medicine, Division of Renal-Electrolyte, Pittsburgh, Pennsylvania
| | - Yonatan Peleg
- Northwestern University Feinberg School of Medicine, Division of Nephrology and Hypertension, Chicago, Illinois
| | - Wooin Ahn
- Oregon Health & Science University School of Medicine, Division of Nephrology and Hypertension, Portland, Oregon, USA
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Bai J, Yin X, Li J, Li JQ, Niu Y, Li Z, Li J, Zhou Y. Incidence, risk factors, and outcomes of recurrent focal segmental glomerulosclerosis in pediatric kidney transplant recipients: A systematic review and meta-analysis. Clin Transplant 2023; 37:e15119. [PMID: 37725070 DOI: 10.1111/ctr.15119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 08/12/2023] [Accepted: 08/23/2023] [Indexed: 09/21/2023]
Abstract
BACKGROUND Focal segmental glomerulosclerosis is the most prevalent acquired kidney disease leading to end-stage renal disease in children and has a propensity for recurring in the transplanted kidney. The recurrence of FSGS after kidney transplantation in children varies greatly. In addition, the risk factors and outcomes of recurrence of FSGS remain controversial. This study evaluated the recurrence rate, risk factors, and prognosis of FSGS after kidney transplantation in order to provide advice and assistance in clinical decision-making for pediatric kidney transplantation. METHODS PubMed, Embase, Web of Science, CNKI, and other databases were searched from the establishment of the repository to March 2022. We extracted data on incidence, risk factors, and outcomes. RESULTS The results showed that the recurrence rate of primary FSGS in children after renal transplantation was 48% (95% CI 36%-59%) and the recurrence rate of FSGS (all forms) was 35% (95% CI 17%-52%). The graft loss rate of primary FSGS in children after kidney transplantation was 29% (95% CI 17%-42%) and the graft loss rate of FSGS (all forms) was 29% (95% CI 4%-62%). 57% (95% CI 42%-73%) of pediatric patients with recurrent primary FSGS showed complete remission. Risk factor analyses showed that age of onset (SMD .69, 95% CI .20-1.19, p = .006) was related to the recurrence of primary FSGS, whereas the living related donor was not a risk factor for recurrent primary FSGS in pediatrics after kidney transplantation (OR 1.22, 95% CI .48-3.10, p = .674). CONCLUSIONS The recurrence rate and graft loss rate of FSGS in children after kidney transplantation were relatively high. Age at onset was associated with a risk for recurrent primary FSGS, whereas the living related donor was not a risk factor for recurrent FSGS in pediatric kidney recipients.
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Affiliation(s)
- Jiang Bai
- Department of Nephrology, Shanxi Provincial People's Hospital (Fifth Hospital) of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xinyu Yin
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Jiaqi Li
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Jia-Qi Li
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yanna Niu
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Zhenhua Li
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Jing Li
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yun Zhou
- Department of Nephrology, Shanxi Provincial People's Hospital (Fifth Hospital) of Shanxi Medical University, Taiyuan, Shanxi, China
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Batal I, Khairallah P, Weins A, Andeen NK, Stokes MB. The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis. Front Immunol 2023; 14:1124249. [PMID: 36911713 PMCID: PMC9995699 DOI: 10.3389/fimmu.2023.1124249] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 02/06/2023] [Indexed: 02/25/2023] Open
Abstract
Primary focal segmental glomerulosclerosis (FSGS), typically characterized by diffuse podocyte foot process effacement and nephrotic syndrome (diffuse podocytopathy), is generally attributed to a circulating permeability factor. Primary FSGS can recur after transplantation where it manifests as diffuse foot process effacement in the early stages, with subsequent evolution of segmental sclerotic lesions. Previous published literature has been limited by the lack of stringent selection criteria to define primary FSGS. Although immunogenetic factors play an important role in many glomerular diseases, their role in recurrent primary FSGS post-transplantation has not been systematically investigated. To address this, we retrospectively studied a multicenter cohort of 74 kidney allograft recipients with end stage kidney disease due to primary FSGS, confirmed by clinical and histologic parameters. After adjusting for race/ethnicity, there was a numeric higher frequency of HLA-A30 antigen in primary FSGS (19%) compared to each of 22,490 healthy controls (7%, adjusted OR=2.0, P=0.04) and 296 deceased kidney donors (10%, OR=2.1, P=0.03). Within the group of transplant patients with end stage kidney disease due to primary FSGS, donor HLA-A30 was associated with recurrent disease (OR=9.1, P=0.02). Multivariable time-to-event analyses revealed that recipients who self-identified as Black people had lower risk of recurrent disease, probably reflecting enrichment of these recipients with APOL1 high-risk genotypes. These findings suggest a role for recipient and donor immunogenetic makeup in recurrent primary FSGS post-transplantation. Further larger studies in well-defined cohorts of primary FSGS that include high-resolution HLA typing and genome-wide association are necessary to refine these hereditary signals.
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Affiliation(s)
- Ibrahim Batal
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, United States
| | - Pascale Khairallah
- Medicine, Division of Nephrology, Columbia University Irving Medical Center, New York, NY, United States
| | - Astrid Weins
- Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
| | - Nicole K Andeen
- Pathology, Oregon Health & Science University, Portland, OR, United States
| | - Michael B Stokes
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, United States
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Miura K, Ando T, Kanda S, Hashimoto T, Kaneko N, Ishizuka K, Hamada R, Hataya H, Hotta K, Gotoh Y, Nishiyama K, Hamasaki Y, Shishido S, Fujita N, Hattori M. Response to steroid and immunosuppressive therapies may predict post-transplant recurrence of steroid-resistant nephrotic syndrome. Pediatr Transplant 2022; 26:e14103. [PMID: 34309142 DOI: 10.1111/petr.14103] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 07/05/2021] [Accepted: 07/19/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Recurrence of SRNS is a major challenge in KT. Several clinical factors, including initial steroid sensitivity, have been associated with increased post-transplant SRNS recurrence risk. However, conflicting data have been reported, possibly due to the heterogeneous pathophysiology of SRNS and the lack of genetic testing of SRNS patients. Furthermore, the response to immunosuppressive therapies has not been evaluated. METHODS Seventy patients aged 1-15 years at SRNS onset who underwent KT between 2002 and 2018 were enrolled. Patients with secondary, familial, syndromic, and genetic forms of SRNS and those who were not treated with steroid were excluded. This study aimed to assess the risk factors for post-transplant recurrence, including treatment responses to initial steroid therapy and additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A. RESULTS Data from 36 kidney transplant recipients were analyzed. Twenty-two (61%) patients experienced post-transplant SRNS recurrence, while 14 patients did not. The proportion of patients who achieved complete or partial remission with initial steroid therapy and/or additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A was significantly higher in the SRNS recurrence group (19/22, 86%) than in the group without SRNS recurrence (6/14, 43%; p = .01). CONCLUSION This study suggests that the response to steroid treatment, other immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A may predict post-transplant SRNS recurrence.
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Affiliation(s)
- Kenichiro Miura
- Department of Pediatric Nephrology, Tokyo Women's Medical University, Tokyo, Japan
| | - Taro Ando
- Department of Pediatric Nephrology, Tokyo Women's Medical University, Tokyo, Japan
| | - Shoichiro Kanda
- Department of Pediatric Nephrology, Tokyo Women's Medical University, Tokyo, Japan.,Department of Pediatrics, The University of Tokyo, Tokyo, Japan
| | - Taeko Hashimoto
- Department of Pediatric Nephrology, Tokyo Women's Medical University, Tokyo, Japan.,Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan
| | - Naoto Kaneko
- Department of Pediatric Nephrology, Tokyo Women's Medical University, Tokyo, Japan
| | - Kiyonobu Ishizuka
- Department of Pediatric Nephrology, Tokyo Women's Medical University, Tokyo, Japan
| | - Riku Hamada
- Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Hiroshi Hataya
- Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Kiyohiko Hotta
- Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Yoshimitsu Gotoh
- Department of Pediatric Nephrology, Japanese Red Cross Nagoya Daini Hospital, Aichi, Japan
| | - Kei Nishiyama
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuko Hamasaki
- Department of Nephrology, Faculty of Medicine, Toho University, Tokyo, Japan
| | - Seiichiro Shishido
- Department of Nephrology, Faculty of Medicine, Toho University, Tokyo, Japan
| | - Naoya Fujita
- Department of Nephrology, Aichi Children's Health and Medical Center, Aichi, Japan
| | - Motoshi Hattori
- Department of Pediatric Nephrology, Tokyo Women's Medical University, Tokyo, Japan
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Harshman LA, Bartosh S, Engen RM. Focal segmental glomerulosclerosis: Risk for recurrence and interventions to optimize outcomes following recurrence. Pediatr Transplant 2022; 26:e14307. [PMID: 35587003 DOI: 10.1111/petr.14307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/14/2022] [Accepted: 04/20/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND FSGS is a common indication for kidney transplant with a high-risk of posttransplant recurrence. METHODS In this review, we summarize current knowledge about FSGS recurrence after kidney transplantation, including epidemiology, pretransplant planning, posttransplant management, and investigational treatments. RESULTS FSGS recurs in 14%-60% of first transplants, likely associated with a circulating permeability factor. Pretransplant counseling regarding recurrence is critical, and patients with FSGS should undergo pretransplant genetic screening. Rapid progression to ESKD, initial steroid responsiveness, younger age at diagnosis, race/ethnicity, and mesangial hypercellularity or minimal change histology on native biopsy may be associated with recurrence. Living donation is not contraindicated but does not result in improved graft survival relative to deceased donation. Pretransplant nephrectomy may be performed for a variety of reasons, but does not decrease recurrence. Pretransplant therapy with rituximab and/or PE is understudied but not clearly effective at preventing recurrence. Patients with FSGS typically present early with rapid-onset severe proteinuria. Diagnosis can be confirmed by biopsy showing foot process effacement; typical FSGS lesions are not seen on light microscopy in the early stages. There is no established effective treatment for recurrent FSGS, but renin-angiotensin-aldosterone system inhibition and extracorporeal therapies, including PE and IA, are most commonly used. Adjunct or alternative therapies may include rituximab, lipopheresis, and cyclosporine.
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Affiliation(s)
- Lyndsay A Harshman
- Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Sharon Bartosh
- University of Wisconsin Madison, Madison, Wisconsin, USA
| | - Rachel M Engen
- University of Wisconsin Madison, Madison, Wisconsin, USA
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Impact of initial steroid response on transplant outcomes in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 2022; 37:1149-1156. [PMID: 34709476 DOI: 10.1007/s00467-021-05270-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 07/18/2021] [Accepted: 08/09/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Limited data suggest children with secondary steroid-resistant nephrotic syndrome (secondary SRNS) have increased risk of recurrence post transplantation. There are no data on the association between secondary steroid resistance and risk of transplant loss. METHODS Children who received kidney transplantation between 2000 and 2019 for either primary or secondary SRNS in Australia and New Zealand were included. Children presenting with nephrotic syndrome before 12 months were excluded. Data were gathered from chart reviews and ANZDATA. Transplant survival was estimated using the Kaplan-Meier estimator with Cox modelling used to explore predictors of survival. RESULTS There were seventy children, 38 (55%) male, median age at presentation 4 years (IQR 2-7) and 46 (66%) Caucasian. Median age at transplant was 11 years (IQR 7-15) and 39 (55%) received living donor transplant. Secondary SRNS occurred in 20/70 (29%). For those with secondary SRNS, 18/20 (90%) had recurrence post-transplant, compared to 18/50 (36%) with primary SRNS (p = 0.001). Every child with history of atopy (n = 11) or with hypoalbuminaemia at time of transplant (n = 13) experienced immediate recurrence. For children with secondary SRNS, 8/18 (44%) with post-transplant recurrence had no response to therapy. For children with primary SRNS, 4/18 (22%) with recurrence had no response to therapy (p = 0.3). Overall, 10-year transplant survival was 47% (95%CI 29-77%) for those with secondary SRNS, compared to 71 (95%CI 57-88%) for those with primary SRNS (p = 0.05). CONCLUSIONS Secondary steroid resistance is strongly associated with SRNS recurrence. Atopy and hypoalbuminaemia at transplant may be novel risk factors for recurrence. Further research is needed to assess if secondary steroid resistance is associated with poorer transplant outcomes. "A higher resolution version of the Graphical abstract is available as Supplementary information".
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Shah S, Joseph C, Srivaths P. Role of therapeutic apheresis in the treatment of pediatric kidney diseases. Pediatr Nephrol 2022; 37:315-328. [PMID: 33991255 DOI: 10.1007/s00467-021-05093-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 04/01/2021] [Accepted: 04/22/2021] [Indexed: 11/26/2022]
Abstract
Therapeutic apheresis utilizes apheresis procedures in the treatment of a variety of conditions including kidney disease. Therapeutic plasma exchange (TPE) is the most common modality employed with the rationale of rapid reduction of a pathogenic substance distributed primarily in the intravascular compartment; however other techniques which adsorb such pathogenic substances or alter the immune profile have been utilized in diseases affecting native and transplanted kidneys. This article discusses the modalities and technical details of therapeutic apheresis and summarizes its role in individual diseases affecting the kidney. Complications related to pediatric apheresis procedures and specifically related to apheresis in kidney disease are also discussed. Though therapeutic apheresis modalities are employed frequently in children with kidney disease, most experiences are extrapolated from adult studies. International and national registries need to be established to elucidate the role of apheresis modalities in children with kidney disease.
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Affiliation(s)
- Shweta Shah
- Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
| | - Catherine Joseph
- Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA
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9
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UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant. Pediatr Nephrol 2022; 37:199-207. [PMID: 34383125 PMCID: PMC8674165 DOI: 10.1007/s00467-021-05248-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 07/23/2021] [Accepted: 07/23/2021] [Indexed: 12/03/2022]
Abstract
BACKGROUND Steroid-resistant nephrotic syndrome (SRNS), commonly caused by focal segmental glomerulosclerosis (FSGS), is associated with progression to stage 5 chronic kidney disease, requirement for kidney replacement therapy and a risk of disease recurrence post-kidney transplantation. Ofatumumab (OFA) is a fully humanised monoclonal antibody to CD20, with similar mechanisms of action to rituximab (RTX). METHODS We report a case series of seven UK patients (five paediatric, two adult), all of whom developed FSGS recurrence after kidney transplantation and received OFA as part of their therapeutic intervention. All also received concomitant plasmapheresis. The 2-year outcome of these seven patients is reported, describing clinical course, kidney function and proteinuria. RESULTS Four patients (all paediatric) achieved complete urinary remission with minimal proteinuria 12 months post-treatment. Three of those four also had normal graft function. Two patients showed partial remission-brief improvement to non-nephrotic proteinuria (197 mg/mmol) in one patient, maintained improvement in kidney function (estimated glomerular filtration rate 76 ml/min/1.73 m2) in the other. One patient did not demonstrate any response. CONCLUSIONS OFA may represent a useful addition to therapeutic options in the management of FSGS recurrence post-transplantation, including where RTX has shown no benefit. Concomitant plasmapheresis in all patients prevents any definitive conclusion that OFA was the beneficial intervention.
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Maniar A, Hooper DK, Sethna CB, Singer P, Traum A, Benoit E, Kotzen E, Verghese P, Garro R, Kamel M, Ranch D, Shih W, Jain NG, Al-Akash S. Re-transplantation in pediatric patients with failure of primary transplant due to recurrent focal segmental glomerulosclerosis: A pediatric nephrology research consortium study. Pediatr Transplant 2021; 25:e14085. [PMID: 34247442 PMCID: PMC8968923 DOI: 10.1111/petr.14085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/20/2021] [Accepted: 06/29/2021] [Indexed: 01/01/2023]
Abstract
INTRODUCTION Recurrent focal and segmental glomerulosclerosis (FSGS) in kidney transplant recipients is associated with lower graft survival and increased morbidity. There are limited data to guide the decision to re-transplant patients with transplant failure due to FSGS recurrence. We aimed to evaluate outcomes in patients re-transplanted after having initial graft failure due to recurrent FSGS and to study physician attitudes and practice patterns. METHODS Retrospective data from 10 centers were collected on 20 patients transplanted between January 1997 and September 2018. A survey was sent to nephrologist members of the Pediatric Nephrology Research Consortium. RESULTS Mean patient age (years) was 9.8 ± 4.8 at first transplant and 15.9 ± 4.9 at re-transplantation. Pre-transplant plasmapheresis was used in 1 (5.3%) primary transplant vs. 7 (38.9%) re-transplants (p = .03). Nephrotic syndrome recurred in 14 patients (70%) after re-transplantation and was severe in 21.1% vs. 64.7% after first transplant (p = .04). Graft survival was significantly higher in the second transplant (p .009) with 70% having functioning grafts at a median of 25.2 months. Thirty-one physicians from 21 centers completed the survey, 94% indicated they would re-transplant such patients, 44.4% preferred a minimum waiting period before re-transplantation, 36.4% preferred living donors, and 22.2% indicated having protocols for re-transplantation at their centers. CONCLUSIONS Consideration for re-transplantation is high among pediatric nephrologists. Pre-transplant plasmapheresis was more frequent in re-transplanted patients. Nephrotic syndrome recurrence was less severe, with better graft survival. More data and a larger population are necessary to further evaluate outcome determinants and best practices in this special population.
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Affiliation(s)
- Aesha Maniar
- Cohen Children’s Medical Center, New Hyde Park, NY, USA
| | - David K. Hooper
- Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | | | - Pamela Singer
- Cohen Children’s Medical Center, New Hyde Park, NY, USA
| | | | | | | | - Priya Verghese
- Ann and Robert H. Lurie Children’s Hospital, Chicago, IL, USA
| | - Rouba Garro
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
| | - Margaret Kamel
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
| | - Daniel Ranch
- University of Texas Health Science Center, San Antonio, TX, USA
| | - Weiwen Shih
- C.S. Mott Children’s Hospital, Ann Arbor, Michigan, USA
| | - Namrata G. Jain
- Columbia University Irving Medical Center, New York, NY, USA
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11
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Mason AE, Saleem MA, Bierzynska A. A critical re-analysis of cases of post-transplantation recurrence in genetic nephrotic syndrome. Pediatr Nephrol 2021; 36:3757-3769. [PMID: 34031708 PMCID: PMC8497325 DOI: 10.1007/s00467-021-05134-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 04/29/2021] [Accepted: 05/12/2021] [Indexed: 11/23/2022]
Abstract
BACKGROUND Genetic defects in podocyte proteins account for up to 30% of steroid-resistant nephrotic syndrome (SRNS) in the paediatric population. Most children with genetic SRNS are resistant to immunosuppression and at high risk of progression to stage 5 chronic kidney disease. Kidney transplantation is often the treatment of choice. The possibility of post-transplantation disease recurrence in genetic SRNS remains controversial, and poses fundamental questions about disease biology. METHODS We critically evaluated the published cases of post-transplantation recurrence in genetic patients, particularly testing 'mutations' against the most recent population variant databases, in order to clarify the diagnoses, and compare the clinical courses and responses to therapy. RESULTS Biallelic pathogenic variants in NPHS1 leading to a complete absence of nephrin were the most commonly reported and best understood instance of nephrotic syndrome occurring post-transplantation. This is an immune-mediated process driven by antibody production against the novel nephrin protein in the allograft. We also identified a number of plausible reported cases of post-transplantation recurrence involving pathogenic variants in NPHS2 (8 patients, biallelic), one in WT1 (monoallelic) and one in NUP93 (biallelic). However, the mechanism for recurrence in these cases remains unclear. Other instances of recurrence in genetic disease were difficult to interpret due to differing clinical criteria, inclusion of patients without true pathogenic variants or the influence of other factors on renal outcome. CONCLUSIONS Overall, post-transplantation recurrence remains very rare in patients with genetic SRNS. It appears to occur later after transplantation than in other patients and usually responds well to plasmapheresis with a good renal outcome.
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Affiliation(s)
- Anna E Mason
- Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK
| | - Moin A Saleem
- Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK.
| | - Agnieszka Bierzynska
- Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK
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12
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Weber LT, Tönshoff B, Grenda R, Bouts A, Topaloglu R, Gülhan B, Printza N, Awan A, Battelino N, Ehren R, Hoyer PF, Novljan G, Marks SD, Oh J, Prytula A, Seeman T, Sweeney C, Dello Strologo L, Pape L. Clinical practice recommendations for recurrence of focal and segmental glomerulosclerosis/steroid-resistant nephrotic syndrome. Pediatr Transplant 2021; 25:e13955. [PMID: 33378587 DOI: 10.1111/petr.13955] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 11/16/2020] [Accepted: 11/23/2020] [Indexed: 12/11/2022]
Abstract
Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence.
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Affiliation(s)
- Lutz T Weber
- Faculty of Medicine, University Hospital of Cologne, Children's and Adolescents' Hospital, Pediatric Nephrology, University of Cologne, Cologne, Germany
| | - Burkhard Tönshoff
- Department of Pediatrics, University Children's Hospital Heidelberg, Heidelberg, Germany
| | - Ryszard Grenda
- Department of Nephrology, Kidney Transplantation & Hypertension, The Children's Memorial Health Institute, Warsaw, Poland
| | - Antonia Bouts
- Department of Pediatric Nephrology, Amsterdam University Medical Center, Emma Children's Hospital, Amsterdam, The Netherlands
| | - Rezan Topaloglu
- Department of Pediatric Nephrology, School of Medicine, Hacettepe University, Ankara, Turkey
| | - Bora Gülhan
- Department of Pediatric Nephrology, School of Medicine, Hacettepe University, Ankara, Turkey
| | - Nikoleta Printza
- 1st Pediatric Department, Pediatric Nephrology Unit, Hippokration General Hospital, Aristotle University, Thessaloniki, Greece
| | - Atif Awan
- Department of Nephrology and Transplantation, Children's Health Ireland, Dublin, Ireland
| | - Nina Battelino
- Pediatric Nephrology Department, Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Rasmus Ehren
- Faculty of Medicine, University Hospital of Cologne, Children's and Adolescents' Hospital, Pediatric Nephrology, University of Cologne, Cologne, Germany
| | - Peter F Hoyer
- Department of Pediatrics II, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
| | - Gregor Novljan
- Pediatric Nephrology Department, Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Stephen D Marks
- UCL Great Ormond Street Institute of Child Health, NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK
| | - Jun Oh
- Department of Pediatrics, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany
| | - Agnieszka Prytula
- Pediatric Nephrology and Rheumatology Department, Ghent University Hospital, Ghent, Belgium
| | - Tomas Seeman
- Department of Pediatrics, 2nd Medical Faculty, Charles University Prague, Prague, Czech Republic.,Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Clodagh Sweeney
- Department of Nephrology and Transplantation, Children's Health Ireland, Dublin, Ireland
| | - Luca Dello Strologo
- Pediatric Renal Transplant Unit, Bambino Gesù Children's Research Hospital, IRCCS, Rome, Italy
| | - Lars Pape
- Department of Pediatrics II, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
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13
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Therapeutic plasma exchange: single-center experience in children with kidney disorders. Pediatr Nephrol 2021; 36:621-629. [PMID: 32949283 DOI: 10.1007/s00467-020-04744-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 07/31/2020] [Accepted: 08/25/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Therapeutic plasma exchange (TPE) is used in kidney diseases as an adjunct treatment. Little has been described as to its effectiveness in kidney disorders in children. This study aimed to assess the safety, efficacy, and outcomes of patients who underwent TPE for kidney indications. METHODS Retrospective chart review of patients receiving TPE from 2010 to 2018 for kidney indications, such as antibody-mediated rejection, bone marrow transplant-associated thrombotic microangiopathy (TA-TMA), atypical hemolytic uremic syndrome, transplant recurrence of focal segmental glomerulosclerosis, and glomerulonephritis. Outcomes assessed were trends in kidney function, mortality, and progression to stage 5 chronic kidney disease (CKD 5). Significant hypocalcemia was defined as ionized calcium < 1 mmol/L. RESULTS A total of 641 TPE procedures were performed on 47 patients (25 male). Average age was 12.8 ± 5.9 years. Median glomerular filtration rate (GFR) improved from baseline to end of TPE treatments (pre 44.9 (19.8, 79), end 56.1 (23, 98) [p = 0.02]). Ten out of 47 children developed CKD 5. Seven out of 47 patients died; 5 had TA-TMA. Initial 7 consecutive sessions were reviewed for complications. Among 335 procedures, 41 episodes of significant hypocalcemia were noted (12.2%); only 1 was symptomatic. Of the 26 episodes (7.7%) of allergic reactions, all were associated with the use of FFP; 5 were anaphylactic. No TPE-associated mortality was noted. CONCLUSIONS TPE is a relatively well-tolerated useful adjunct therapy in children with kidney indications. The benefit of TPE has to be balanced with risks such as hypocalcemia and allergic reactions which can occur more frequently with FFP. Graphical abstract.
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14
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Al-Jehani MH, Al-Husayni F, Aljabri A, AlMaghraby HQ, Banamah TA. Cyclophosphamide as a Treatment for Focal Segmental Glomerular Sclerosis Recurrence in a Kidney Transplant Patient. AMERICAN JOURNAL OF CASE REPORTS 2021; 22:e929097. [PMID: 33539328 PMCID: PMC7871296 DOI: 10.12659/ajcr.929097] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Patient: Female, 24-year-old Final Diagnosis: Focal segmental glomerulosclerosis Symptoms: Facia • lower extremity edema Medication: — Clinical Procedure: — Specialty: Nephrology
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Affiliation(s)
- Mariann H Al-Jehani
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Faisal Al-Husayni
- Department of Internal Medicine, National Guard Hospital, King Abdulaziz Medical City, Jeddah, Saudi Arabia.,Department of Internal Medicine, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Abdullah Aljabri
- Department of Internal Medicine, National Guard Hospital, King Abdulaziz Medical City, Jeddah, Saudi Arabia.,Department of Internal Medicine, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Hatim Qasim AlMaghraby
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia.,Department of Pathology, National Guard Hospital, King Abdulaziz Medical City, Jeddah, Saudi Arabia.,Department of Pathology, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Turki A Banamah
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia.,Department of Nephrology, National Guard Hospital, Jeddah, Saudi Arabia.,Department of Nephrology, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
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15
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16
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Factors Influencing Disease Recurrence and Graft Survival in Patients who Developed End-Stage Renal Disease Due to Focal Segmental Glomerulosclerosis and Underwent Renal Transplantation. Int Surg 2021. [DOI: 10.9738/intsurg-d-15-00154.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Aim
The aim of our study was to determine the factors effecting disease recurrence and graft survival in patients who developed end-stage renal disease (ESRD) due to focal segmental glomerulosclerosis (FSGS) and underwent renal transplantation (Rtx).
Methods
A total of 37 patients with FSGS (female/male: 10/27) who underwent Rtx in our transplant center between 2001 and 2014 were included in the study. The patients were diagnosed with FSGS by biopsy. Comparative analyses were performed in order to determine the factors effecting disease recurrence and graft survival. Plasmapheresis was performed with 40 mL/kg plasma. The diagnosis of the recurrence of FSGS and the acute rejections were also confirmed by biopsy.
Results
Statistical analyses revealed that, recurrence rates were higher in Rtx recipients from deceased donor [deceased donor versus living donor, 2 (50.0%) versus 3 (9.1%), P = 0.024]. However, no correlation was found between recurrence and renal replacement treatment (RRT) methods, duration of RRT, preoperative or postoperative prophylactic plasmapheresis, the presence of preoperative nephrotic proteinuria, donor's or recipient's age or gender, kinship with donor, time interval between development of FSGS and ESRD, or performing native nephrectomy. Graft survival rates were higher in Rtx patients that were transplanted from living donor, first-degree relatives, and in patients without recurrence.
Conclusion
In countries where organ donation is insufficient, living donors can be used with a low risk of recurrence for Rtx candidates with FSGS. Also, grafts from living donors, particularly from first-degree relatives, have higher survival rates.
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17
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Kidney transplantation for primary glomerulonephritis: Recurrence risk and graft outcomes with related versus unrelated donors. Transplant Rev (Orlando) 2020; 35:100584. [PMID: 33069562 DOI: 10.1016/j.trre.2020.100584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 10/06/2020] [Accepted: 10/09/2020] [Indexed: 11/20/2022]
Abstract
Primary glomerulonephritis can recur after kidney transplantation and may jeopardize the survival of the renal allograft. The risks of living-related kidney transplantation remain controversial in this group of patients. Living related transplantation offers potentially better HLA matching, therefore improve the long-term graft survival. However, the concern for increased rates of recurrence of the primary glomerulonephritis in the transplanted kidney from living related donors complicates the selection of donors. With the recent dramatic rise in the use of paired kidney exchange, there is now often the option of having a living related donor donate through a paired exchange. This raises the question of whether patients with primary glomerulonephritis should receive living donor kidneys through paired kidney exchange programs to obtain the benefits of a living donor kidney transplant while also reducing the risk of recurrent glomerulonephritis. Our review of the literature suggests that although the recurrence of primary glomerulonephritis occurs more often when donation occurs from a living related donor as compared to an unrelated donor, the graft survival advantage of living related donation is generally maintained despite the recurrence. We suggest that despite the increased risk of recurrence, living related donation should not be avoided in patients with primary glomerulonephritis as the cause of their end-stage renal disease.
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18
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Raina R, Joshi H, Chakraborty R. Changing the terminology from kidney replacement therapy to kidney support therapy. Ther Apher Dial 2020; 25:437-457. [PMID: 32945598 DOI: 10.1111/1744-9987.13584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 08/16/2020] [Accepted: 09/12/2020] [Indexed: 11/28/2022]
Abstract
Kidney replacement therapy (KRT) is a common supportive treatment for renal dysfunction, especially acute kidney injury. However, critically ill or immunosuppressed patients with renal dysfunction often have dysfunction in other organs as well. To improve patient outcomes, clinicians began to initiate kidney replacement therapy in situations where nonrenal conditions may lead to acute kidney injury, such as septic shock, hematopoietic stem cell transplantation, veno-occlusive renal disease, cardiopulmonary bypass, chemotherapy, tumor lysis syndrome, hyperammonemia, and various others. In this review, we discuss the use of various modes of kidney replacement therapy in treating renal and nonrenal complications to illustrate why kidney support therapy is a more appropriate terminology than kidney replacement therapy.
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Affiliation(s)
- Rupesh Raina
- Department of Nephrology, Cleveland Clinic Akron General/Akron Nephrology Associates, Akron, Ohio, USA.,Department of Nephrology, Akron Children's Hospital, Akron, Ohio, USA
| | - Hirva Joshi
- Northeast Ohio Medical University, Rootstown, Ohio, USA
| | - Ronith Chakraborty
- Department of Nephrology, Cleveland Clinic Akron General/Akron Nephrology Associates, Akron, Ohio, USA
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19
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Infante B, Rossini M, Leo S, Troise D, Netti GS, Ranieri E, Gesualdo L, Castellano G, Stallone G. Recurrent Glomerulonephritis after Renal Transplantation: The Clinical Problem. Int J Mol Sci 2020; 21:ijms21175954. [PMID: 32824988 PMCID: PMC7504691 DOI: 10.3390/ijms21175954] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 07/30/2020] [Accepted: 08/17/2020] [Indexed: 12/22/2022] Open
Abstract
Glomerulonephritis (GN) continues to be one of the main causes of end-stage kidney disease (ESKD) with an incidence rating from 10.5% to 38.2%. Therefore, recurrent GN, previously considered to be a minor contributor to graft loss, is the third most common cause of graft failure 10 years after renal transplantation. However, the incidence, pathogenesis, and natural course of recurrences are still not completely understood. This review focuses on the most frequent diseases that recur after renal transplantation, analyzing rate of recurrence, epidemiology and risk factors, pathogenesis and bimolecular mechanisms, clinical presentation, diagnosis, and therapy, taking into consideration the limited data available in the literature. First of all, the risk for recurrence depends on the type of glomerulonephritis. For example, recipient patients with anti-glomerular basement membrane (GBM) disease present recurrence rarely, but often exhibit rapid graft loss. On the other hand, recipient patients with C3 glomerulonephritis present recurrence in more than 50% of cases, although the disease is generally slowly progressive. It should not be forgotten that every condition that can lead to chronic graft dysfunction should be considered in the differential diagnosis of recurrence. Therefore, a complete workup of renal biopsy, including light, immunofluorescence and electron microscopy study, is essential to provide the diagnosis, excluding alternative diagnosis that may require different treatment. We will examine in detail the biomolecular mechanisms of both native and transplanted kidney diseases, monitoring the risk of recurrence and optimizing the available treatment options.
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Affiliation(s)
- Barbara Infante
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto Luigi 251, 71122 Foggia, Italy; (B.I.); (S.L.); (D.T.); (G.S.)
| | - Michele Rossini
- Clinical Pathology Unit and Center of Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto, 71122 Foggia, Italy; (M.R.); (G.S.N.); (E.R.)
| | - Serena Leo
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto Luigi 251, 71122 Foggia, Italy; (B.I.); (S.L.); (D.T.); (G.S.)
| | - Dario Troise
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto Luigi 251, 71122 Foggia, Italy; (B.I.); (S.L.); (D.T.); (G.S.)
| | - Giuseppe Stefano Netti
- Clinical Pathology Unit and Center of Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto, 71122 Foggia, Italy; (M.R.); (G.S.N.); (E.R.)
| | - Elena Ranieri
- Clinical Pathology Unit and Center of Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto, 71122 Foggia, Italy; (M.R.); (G.S.N.); (E.R.)
| | - Loreto Gesualdo
- Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy;
| | - Giuseppe Castellano
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto Luigi 251, 71122 Foggia, Italy; (B.I.); (S.L.); (D.T.); (G.S.)
- Correspondence: ; Tel.: +39-0881732610; Fax: +39-0881736001
| | - Giovanni Stallone
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto Luigi 251, 71122 Foggia, Italy; (B.I.); (S.L.); (D.T.); (G.S.)
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20
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Morello W, Puvinathan S, Puccio G, Ghiggeri GM, Dello Strologo L, Peruzzi L, Murer L, Cioni M, Guzzo I, Cocchi E, Benetti E, Testa S, Ghio L, Caridi G, Cardillo M, Torelli R, Montini G. Post-transplant recurrence of steroid resistant nephrotic syndrome in children: the Italian experience. J Nephrol 2020; 33:849-857. [PMID: 31617157 PMCID: PMC7381476 DOI: 10.1007/s40620-019-00660-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 10/09/2019] [Indexed: 11/29/2022]
Abstract
BACKGROUND Steroid resistant nephrotic syndrome (SRNS) is a frequent cause of end stage renal disease in children and post-transplant disease recurrence is a major cause of graft loss. METHODS We identified all children with SRNS who underwent renal transplantation in Italy, between 2005 and 2017. Data were retrospectively collected for the presence of a causative gene mutation, sex, histology, duration of pre-transplant dialysis, age at onset and transplant, HLA matching, recurrence, therapy for recurrence, and graft survival. RESULTS 101 patients underwent a first and 22 a second renal transplant. After a median follow-up of 58.5 months, the disease recurred on the first renal transplant in 53.3% of patients with a non-genetic and none with a genetic SRNS. Age at transplant > 9 years and the presence of at least one HLA-AB match were independent risk factors for recurrence. Duration of dialysis was longer in children with relapse, but did not reach statistical significance. Overall, 24% of patients lost the first graft, with recurrence representing the commonest cause. Among 22 patients who underwent a second transplant, 5 suffered of SRNS recurrence. SRNS relapsed in 5/9 (55%) patients with disease recurrence in their first transplant and 2 of them lost the second graft. CONCLUSIONS Absence of a causative mutation represents the major risk factor for post-transplant recurrence in children with SRNS, while transplant can be curative in genetic SRNS. A prolonged time spent on dialysis before transplantation has no protective effect on the risk of relapse and should not be encouraged. Retransplantation represents a second chance after graft loss for recurrence.
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Affiliation(s)
- William Morello
- Pediatric Nephrology, Dialysis and Transplant Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, via della Commenda, 9, 20122, Milan, Italy
| | - Sairaj Puvinathan
- Pediatric Nephrology, Dialysis and Transplant Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, via della Commenda, 9, 20122, Milan, Italy
| | - Giuseppe Puccio
- Pediatric Nephrology, Dialysis and Transplant Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, via della Commenda, 9, 20122, Milan, Italy
| | - Gian Marco Ghiggeri
- Division of Nephrology, Dialysis, and Transplantation, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Luca Dello Strologo
- Renal Transplant Unit, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy
| | - Licia Peruzzi
- Pediatric Nephrology Unit, Regina Margherita Children's Hospital, Città della Salute e della Scienza di Torino, Turin, Italy
| | - Luisa Murer
- Pediatric Nephrology, Dialysis and Transplant Unit, Department of Women's and Children's Health, Hospital-University of Padova, Padua, Italy
| | - Michela Cioni
- Division of Nephrology, Dialysis, and Transplantation, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Isabella Guzzo
- Renal Transplant Unit, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy
| | - Enrico Cocchi
- Pediatric Nephrology Unit, Regina Margherita Children's Hospital, Città della Salute e della Scienza di Torino, Turin, Italy
| | - Elisa Benetti
- Pediatric Nephrology, Dialysis and Transplant Unit, Department of Women's and Children's Health, Hospital-University of Padova, Padua, Italy
| | - Sara Testa
- Pediatric Nephrology, Dialysis and Transplant Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, via della Commenda, 9, 20122, Milan, Italy
| | - Luciana Ghio
- Pediatric Nephrology, Dialysis and Transplant Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, via della Commenda, 9, 20122, Milan, Italy
| | - Gianluca Caridi
- Division of Nephrology, Dialysis, and Transplantation, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Massimo Cardillo
- North Italy Transplant program (NITp), UOC Coordinamento Trapianti, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | - Rosanna Torelli
- North Italy Transplant program (NITp), UOC Coordinamento Trapianti, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | - Giovanni Montini
- Pediatric Nephrology, Dialysis and Transplant Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, via della Commenda, 9, 20122, Milan, Italy.
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21
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Demir ME, Uyar M, Merhametsiz O. Combination of High-Dose Intravenous Cyclosporine and Plasma Exchange Treatment Is Effective in Post-Transplant Recurrent Focal Segmental Glomerulosclerosis: Results of Case Series. Transplant Proc 2020; 52:843-849. [PMID: 32199645 DOI: 10.1016/j.transproceed.2020.01.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 12/25/2019] [Accepted: 01/10/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND Idiopathic focal segmental glomerulosclerosis (FSGS) commonly recurs in the early post-transplant period. The treatment protocols and results are conflictive in recurrent FSGS. We aimed to present the results of our treatment protocol and basic approach to the disease recurrences. METHODS This prospective, single-center study was conducted between the years 2015 and 2018. Twelve patients who fit completely the diagnosis of idiopathic FSGS by clinical, laboratory, and biopsy findings were included. A specific treatment protocol which consists of plasma exchange and high dose intravenous cyclosporine was delivered to the patients independently of induction protocols. Twenty-four months of outcomes of graft functions were evaluated. RESULTS Nine patients completed the treatment protocol and were documented for evaluation. All patients achieved a complete or partial remission in an average 24 months of follow-up period. CONCLUSION Idiopathic FSGS is more commonly recurrent than thought to be. The early detection of proteinuria is crucial because the administration of a plasma exchange-based treatment protocol can reverse proteinuria. We think our treatment protocol is a well-established, efficient, and safe choice for post-transplant recurrent FSGS in adults.
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Affiliation(s)
- Mehmet Emin Demir
- Yeni Yuzyil University, Private Gaziosmanpasa Hospital, Department of Nephrology and Organ Transplantation, Istanbul, Turkey.
| | - Murathan Uyar
- Yeni Yuzyil University, Private Gaziosmanpasa Hospital, Department of Nephrology and Organ Transplantation, Istanbul, Turkey
| | - Ozgur Merhametsiz
- Yeni Yuzyil University, Private Gaziosmanpasa Hospital, Department of Nephrology and Organ Transplantation, Istanbul, Turkey
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22
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Uffing A, Pérez-Sáez MJ, Mazzali M, Manfro RC, Bauer AC, de Sottomaior Drumond F, O'Shaughnessy MM, Cheng XS, Chin KK, Ventura CG, Agena F, David-Neto E, Mansur JB, Kirsztajn GM, Tedesco-Silva H, Neto GMV, Arias-Cabrales C, Buxeda A, Bugnazet M, Jouve T, Malvezzi P, Akalin E, Alani O, Agrawal N, La Manna G, Comai G, Bini C, Muhsin SA, Riella MC, Hokazono SR, Farouk SS, Haverly M, Mothi SS, Berger SP, Cravedi P, Riella LV. Recurrence of FSGS after Kidney Transplantation in Adults. Clin J Am Soc Nephrol 2020; 15:247-256. [PMID: 31974287 PMCID: PMC7015092 DOI: 10.2215/cjn.08970719] [Citation(s) in RCA: 113] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 11/29/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. RESULTS Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0-8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival. CONCLUSIONS Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.
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Affiliation(s)
- Audrey Uffing
- Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.,Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Maria José Pérez-Sáez
- Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.,Servicio de Nefrología, Hospital del Mar, Barcelona, Spain
| | - Marilda Mazzali
- Division of Nephrology, School of Medical Sciences, University of Campinas (UNICAMP), Sao Paulo, Brazil
| | - Roberto C Manfro
- Division of Nephrology, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Andrea Carla Bauer
- Division of Nephrology, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | | | - Michelle M O'Shaughnessy
- Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California
| | - Xingxing S Cheng
- Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California
| | - Kuo-Kai Chin
- Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California
| | - Carlucci G Ventura
- Kidney Transplant Service, Hospital das Clinicas-University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Fabiana Agena
- Kidney Transplant Service, Hospital das Clinicas-University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Elias David-Neto
- Kidney Transplant Service, Hospital das Clinicas-University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Juliana B Mansur
- Division of Nephrology, Hospital do Rim, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | | | - Helio Tedesco-Silva
- Division of Nephrology, Hospital do Rim, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - Gilberto M V Neto
- Division of Nephrology, Hospital do Rim, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | | | - Anna Buxeda
- Servicio de Nefrología, Hospital del Mar, Barcelona, Spain
| | - Mathilde Bugnazet
- Service de Néphrologie Dialyse, Aphérèses et Transplantation, Grenoble University Hospital, Grenoble, France
| | - Thomas Jouve
- Service de Néphrologie Dialyse, Aphérèses et Transplantation, Grenoble University Hospital, Grenoble, France
| | - Paolo Malvezzi
- Service de Néphrologie Dialyse, Aphérèses et Transplantation, Grenoble University Hospital, Grenoble, France
| | - Enver Akalin
- Montefiore Einstein Center for Transplantation, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
| | - Omar Alani
- Montefiore Einstein Center for Transplantation, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
| | - Nikhil Agrawal
- Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Gaetano La Manna
- Department of Experimental Diagnostic and Specialty Medicine (DIMES), Nephrology, Dialysis and Renal Transplant Unit, St. Orsola Hospital, University of Bologna, Bologna, Italy
| | - Giorgia Comai
- Department of Experimental Diagnostic and Specialty Medicine (DIMES), Nephrology, Dialysis and Renal Transplant Unit, St. Orsola Hospital, University of Bologna, Bologna, Italy
| | - Claudia Bini
- Department of Experimental Diagnostic and Specialty Medicine (DIMES), Nephrology, Dialysis and Renal Transplant Unit, St. Orsola Hospital, University of Bologna, Bologna, Italy
| | - Saif A Muhsin
- Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | | | | | - Samira S Farouk
- Renal Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Meredith Haverly
- Renal Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Suraj Sarvode Mothi
- Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Stefan P Berger
- Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Paolo Cravedi
- Renal Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Leonardo V Riella
- Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
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23
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Li M, Alfieri CM, Morello W, Cellesi F, Armelloni S, Mattinzoli D, Montini G, Messa P. Assessment of increased glomerular permeability associated with recurrent focal segmental glomerulosclerosis using an in vitro model of the glomerular filtration barrier. J Nephrol 2019; 33:747-755. [PMID: 31853790 DOI: 10.1007/s40620-019-00683-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 12/02/2019] [Indexed: 11/25/2022]
Abstract
The presence of circulating permeability factors (cPFs) has been hypothesized to be associated with recurrence of focal segmental glomerulosclerosis (rFSGS) in renal allografts. The available methods to detect cPFs are complex, not easily repeatable and inappropriate to represent the anatomical characteristics of the three-layer glomerular filtration barrier (GFB). Here we describe a novel method which measures the permeability to bovine serum albumin (BSA) through a three-layer device (3LD). The 3 layers comprise: (1) conditionally immortalized human podocytes (HCiPodo), (2) collagen type IV coated porous membrane and (3) human glomerular endothelial cells (HCiGEnC). Using this method, we found that sera from all rFSGS patients increased albumin permeability, while sera from non recurrent (nrFSGS) and genetic (gFSGS) forms of FSGS did not. The mechanisms underlying the increase of albumin permeability are probably due to endothelial cell damage as an initial event, which was demonstrated by the decrease of Platelet endothelial cell adhesion molecule (PECAM-1 or CD31), while the podocytes' expressions of synaptopodin and podocin were normal. Furthermore, we also found that the plasmapheretic treatment (PPT) eliminated the effect of increasing BSA permeability in sera from rFSGS patients. These preliminary data suggest that our in vitro GFB model could not only be useful in predicting the recurrence of FSGS after renal transplantation (RTx), but also be a valuable in vitro model to study podocyte and endothelial cell biology.
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Affiliation(s)
- Min Li
- IRCCS Ospedale Maggiore Policlinico, Renal Research Laboratory, Foundation Ca' Granda, Milan, Italy
| | - Carlo Maria Alfieri
- Unit of Adult Nephrology, Dialysis and Renal Transplant, Department of Medicine, Foundation Ca' Granda IRCCS Ospedale Maggiore Policlinico, Via Commenda 15, 20122, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli studi di Milano, Milan, Italy
| | - William Morello
- Pediatric Nephrology, Dialysis and Transplant Unit, Foundation IRCCS Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy
| | - Francesco Cellesi
- Politecnico di Milano, Dipartimento di Chimica, Materiali ed Ingegneria Chimica "G. Natta", Milan, Italy
| | - Silvia Armelloni
- IRCCS Ospedale Maggiore Policlinico, Renal Research Laboratory, Foundation Ca' Granda, Milan, Italy
| | - Deborah Mattinzoli
- IRCCS Ospedale Maggiore Policlinico, Renal Research Laboratory, Foundation Ca' Granda, Milan, Italy
| | - Giovanni Montini
- Pediatric Nephrology, Dialysis and Transplant Unit, Foundation IRCCS Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli studi di Milano, Milan, Italy
| | - Piergiorgio Messa
- Unit of Adult Nephrology, Dialysis and Renal Transplant, Department of Medicine, Foundation Ca' Granda IRCCS Ospedale Maggiore Policlinico, Via Commenda 15, 20122, Milan, Italy.
- Department of Clinical Sciences and Community Health, Università degli studi di Milano, Milan, Italy.
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24
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Salvadori M, Tsalouchos A. Therapeutic apheresis in kidney transplantation: An updated review. World J Transplant 2019; 9:103-122. [PMID: 31750088 PMCID: PMC6851502 DOI: 10.5500/wjt.v9.i6.103] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 10/02/2019] [Accepted: 10/15/2019] [Indexed: 02/05/2023] Open
Abstract
Therapeutic apheresis is a cornerstone of therapy for several conditions in transplantation medicine and is available in different technical variants. In the setting of kidney transplantation, immunological barriers such as ABO blood group incompatibility and preformed donor-specific antibodies can complicate the outcome of deceased- or living- donor transplantation. Postoperatively, additional problems such as antibody-mediated rejection and a recurrence of primary focal segmental glomerulosclerosis can limit therapeutic success and decrease graft survival. Therapeutic apheresis techniques find application in these issues by separating and selectively removing exchanging or modifying pathogenic material from the patient by an extracorporeal aphaeresis system. The purpose of this review is to describe the available techniques of therapeutic aphaeresis with their specific advantages and disadvantages and examine the evidence supporting the application of therapeutic aphaeresis as an adjunctive therapeutic option to immunosuppressive agents in protocols before and after kidney transplantation.
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Affiliation(s)
- Maurizio Salvadori
- Department of Transplantation Renal Unit, Careggi University Hospital, Florence 50139, Italy
| | - Aris Tsalouchos
- Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
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25
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Auñón P, Polanco N, Pérez-Sáez MJ, Rodrigo E, Sancho A, Pascual J, Andrés A, Praga M. Pre-emptive rituximab in focal and segmental glomerulosclerosis patients at risk of recurrence after kidney transplantation. Clin Kidney J 2019; 14:139-148. [PMID: 33564412 PMCID: PMC7857812 DOI: 10.1093/ckj/sfz120] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2019] [Accepted: 08/08/2019] [Indexed: 12/12/2022] Open
Abstract
Background The recurrence of proteinuria after kidney transplantation (KT) is a characteristic complication of focal segmental glomerulosclerosis (FSGS). It has been suggested that pre-emptive rituximab might prevent recurrences in patients at risk, but there is no agreement about which factors might help to identify such patients. Methods We studied 93 kidney transplants with biopsy-proven idiopathic FSGS in order to analyse if preventive rituximab treatment could decrease recurrences in patients at risk. Results Fifteen patients (16.1%) presented a recurrence after KT, but when we restricted the analysis to the 34 patients presenting nephrotic syndrome at primary disease onset, the recurrence diagnosis rate increased to 44.1%. All patients with recurrence had complete nephrotic syndrome at the time of diagnosis. After multivariate adjustment, the only significant risk factor for recurrence was the presence of complete nephrotic syndrome at diagnosis. Twelve of the 34 patients at risk for recurrence received rituximab at the time of transplantation. Clinical and analytical characteristics were similar in all patients at risk. The number of recurrences was similar among treated (50%) and non-treated patients (40.9%). Conclusions Nephrotic syndrome with hypoalbuminaemia at diagnosis is the most important feature to identify patients at risk of recurrence. Our data suggest that pre-emptive rituximab is not effective to prevent FSGS recurrences.
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Affiliation(s)
- Pilar Auñón
- Nephrology Department, Hospital Doce de Octubre, Madrid, Spain
| | - Natalia Polanco
- Nephrology Department, Hospital Doce de Octubre, Madrid, Spain
| | | | - Emilio Rodrigo
- Nephrology Department, Hospital Marqués de Valdecilla, Santander, Spain
| | - Asunción Sancho
- Nephrology Department, Hospital Doctor Peset, Valencia, Spain
| | - Julio Pascual
- Nephrology Department, Hospital del Mar, Barcelona, Spain
| | - Amado Andrés
- Nephrology Department, Hospital Doce de Octubre, Madrid, Spain
| | - Manuel Praga
- Nephrology Department, Hospital Doce de Octubre, Madrid, Spain.,Department of Medicine, Complutense University, Madrid, Spain
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26
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Mansur JB, Sandes-Freitas TV, Kirsztajn GM, Cristelli MP, Mata GF, de Paula MI, Grenzi PC, Martins SBS, Felipe CR, Tedesco-Silva H, Pestana JOM. Clinical features and outcomes of kidney transplant recipients with focal segmental glomerulosclerosis recurrence. Nephrology (Carlton) 2019; 24:1179-1188. [PMID: 30891898 DOI: 10.1111/nep.13589] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/12/2019] [Indexed: 11/29/2022]
Abstract
AIM Focal segmental glomerulosclerosis recurs in up to 30% and up to 80% of adult and pediatric kidney transplant recipients, respectively. There is no standard of care treatment. The purpose of this study was to evaluate clinical characteristics, treatments and outcomes of patients with focal segmental glomerulosclerosis recurrence (FSGSr). METHODS This was a retrospective single-center cohort study including FSGSr patients treated with plasmapheresis (PP) and combinations of high dose steroids, cyclosporine and rituximab. RESULTS Among 61 patients included in this analysis the median time to diagnosis was 19 days. The incidence of first biopsy-confirmed FSGSr was 18% reaching 52.4% with follow-up biopsies. During PP treatment 54% of the patients developed infectious complications. PP was discontinued in 37% of patients due to treatment failure (no remission or graft loss) and in 26% due to an adverse event. All patients who discontinued PP due to adverse event did not show clinical response or lost the allograft. The incidence of acute rejection was 34.4%. The incidences of partial and complete remissions were 16.4% and 27.8%, respectively. Overall 6-years patient and graft survivals were 90.7% and 64.5%, respectively. CONCLUSION This analysis confirms the low, variable and unpredictable rate of FSGSr remission, inconsistencies among available therapeutic options and its high rate of adverse events, and the negative impact on graft survival.
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Affiliation(s)
- Juliana B Mansur
- Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | | | - Gianna M Kirsztajn
- Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - Marina P Cristelli
- Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - Gustavo F Mata
- Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - Mayara I de Paula
- Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - Patricia C Grenzi
- Microbiology and Immunology Division, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Suelen B S Martins
- Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - Claudia R Felipe
- Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - Hélio Tedesco-Silva
- Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - José O M Pestana
- Nephrology Division, Hospital do Rim, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
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27
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Alhasan KA, Alherbish A, Osman A, Kari JA, Almojalli H. Successful Treatment of Recurrent Focal Segmental Glomerulosclerosis After Transplantation in Children: A Single-Center Experience. Transplant Proc 2019; 51:517-521. [PMID: 30879580 DOI: 10.1016/j.transproceed.2019.01.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE We aim to report our experience managing cases of recurrent focal segmental glomerulosclerosis (FSGS) in a group of pediatric renal transplant recipients. METHODS This study was a retrospective chart review of pediatric patients who had their first kidney transplant at King Faisal Specialist Hospital & Research Center between 2014 and 2016. RESULTS We reviewed the files of 6 patients, 3 of whom were male. The median age of the children was 2.75 years (range, 2-4 years) at disease onset, with an average time of progression to end-stage renal disease of 19 months (range, 8-30 months). Five of the patients received a living related donor transplant, and 1 received a living nonrelated donor transplant. Patients had FSGS recurrence at varying intervals (1 to 3 days) post transplant. All cases had plasmapheresis prior to receiving abatacept or rituximab. The therapeutic strategy in 4 patients involved switching tacrolimus to cyclosporine. A complete response was observed in 5 of the 6 patients (83.3%), and treatment was well tolerated in 5 patients. Patient 1 had severe oliguria and required intermittent hemodialysis during the first 3 weeks post transplant. He showed minimal response to the therapeutic plasma exchange and rituximab and was subsequently treated with abatacept. However, he died 8 months post transplant of pneumonia and sepsis. CONCLUSION Rituximab and switching tacrolimus to cyclosporine, in conjunction with plasmapheresis, appeared to be effective and safe in children with recurrent FSGS. Conversely, abatacept did not appear to provide clinical benefit.
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Affiliation(s)
- K A Alhasan
- Department of Pediatrics, College of Medicine, King Saud University, King Khalid University Hospital, Riyadh, Saudi Arabia; Organ Transplant Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
| | - A Alherbish
- Department of Pediatrics, College of Medicine, King Saud University, King Khalid University Hospital, Riyadh, Saudi Arabia; Organ Transplant Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
| | - A Osman
- Department of Pediatrics, College of Medicine, King Saud University, King Khalid University Hospital, Riyadh, Saudi Arabia
| | - J A Kari
- Pediatric Nephrology Center of Excellence and Department of Pediatrics, King Abdulaziz University, Jeddah, Saudi Arabia
| | - H Almojalli
- Organ Transplant Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
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28
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Bulut IK, Taner S, Keskinoglu A, Toz H, Sarsik B, Sezer TO, Kabasakal C. Long-Term Follow-up Results of Renal Transplantation in Pediatric Patients With Focal Segmental Glomerulosclerosis: A Single-Center Experience. Transplant Proc 2019; 51:1064-1069. [PMID: 31101172 DOI: 10.1016/j.transproceed.2019.01.096] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2018] [Accepted: 01/21/2019] [Indexed: 10/27/2022]
Abstract
INTRODUCTION AND AIM Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage renal disease in children. We analyzed the long-term outcome of pediatric patients with FSGS undergoing renal transplantation. The objective of the study is to report the experience of a single center and determine the incidence of recurrence, rejection, graft loss, and related risk factors. MATERIALS AND METHOD This retrospective cohort study was performed between 1991 and 2018. Thirty patients with a pathologic diagnosis of primary FSGS were included in the study. The patients were diagnosed with FSGS according to histologic features in biopsies. RESULTS Twenty-one of the donors were deceased (70%) and 9 were alive (30%). FSGS recurred in only 2 patients. Graft loss occurred in 6 patients (20%). The causes of graft loss were chronic rejection in 4 patients and acute rejection in 2. Our graft survival rate was 100% at 1 year, 91% at 5 years, 80% at 10 years, 70% at 15 years, and 42% at 20 years. Five- and 10-year graft survival rates were 83% and 83% in living donors and 94% and 79% in deceased donors, respectively. According to Kaplan-Meier analysis, there was no statistically significant difference in terms of graft survival between living and deceased donors. CONCLUSION This study, with its contribution to literature in terms of long follow-up of FSGS patients from childhood to adulthood, is important. However, further studies are required.
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Affiliation(s)
- I K Bulut
- Department of Pediatric Nephrology, Ege University Faculty of Medicine, İzmir, Turkey.
| | - S Taner
- Department of Pediatric Nephrology, Ege University Faculty of Medicine, İzmir, Turkey
| | - A Keskinoglu
- Department of Pediatric Nephrology, Ege University Faculty of Medicine, İzmir, Turkey
| | - H Toz
- Department of Nephrology, Ege University Faculty of Medicine, İzmir, Turkey
| | - B Sarsik
- Department of Pathology, Ege University Faculty of Medicine, İzmir, Turkey
| | - T O Sezer
- Department of General Surgery, Ege University Faculty of Medicine, İzmir, Turkey
| | - C Kabasakal
- Department of Pediatric Nephrology, Ege University Faculty of Medicine, İzmir, Turkey
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29
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Deriving and understanding the risk of post-transplant recurrence of nephrotic syndrome in the light of current molecular and genetic advances. Pediatr Nephrol 2018; 33:2027-2035. [PMID: 29022104 PMCID: PMC6153493 DOI: 10.1007/s00467-017-3793-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 08/22/2017] [Indexed: 12/31/2022]
Abstract
After renal transplantation, recurrence of the original disease is the second most common cause of graft loss, after rejection. The most dramatic manifestation of this phenomenon is in patients with nephrotic syndrome (NS). NS is a descriptive term describing a clinical picture centred on proteinuria arising from damage to the glomerular filtration barrier (GFB). There are many different drivers of that damage, ranging from immune dysregulation to genetic disorders and chronic disease/infections. The main categories in childhood are "idiopathic" (presumed immune mediated) and genetic NS, with further stratification of the idiopathic group according to steroid responses. A significant proportion of patients with NS progress to established renal failure, requiring transplantation, and one of the most difficult clinical scenarios faced by nephrologists is the recurrence of the original disease in up to 50% of patients, usually rapidly post-transplant. This is thought to be the archetypal "circulating factor" disease, in which as yet unknown circulating plasma "factor(s)" in the recipient target the donor kidney. The ability to predict in advance which patients will suffer recurrence would enhance our ability to counsel patients and families, and potentially identify those patients before transplant for tailored immunosuppressive preparation. Until very recently, stratification based on clinical categorisations has been poor in being able to predict those patients in whom disease will recur, and laboratory biomarkers are yet to be adequately refined. However, by mapping our growing understanding of disease mechanisms to clinical phenotypes, and with greatly improved genetic diagnostics, we have made progress in being able to stratify patients more specifically, and allow better predictive algorithms to be developed. Using our knowledge of podocyte biology, circulating factor-induced specific biomarkers are also being tested. This review is aimed at outlining those advances, and suggesting how we can move further forward in both clinical and biological markers of disease type.
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30
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Abbas F, El Kossi M, Jin JK, Sharma A, Halawa A. Recurrence of primary glomerulonephritis: Review of the current evidence. World J Transplant 2017; 7:301-316. [PMID: 29312859 PMCID: PMC5743867 DOI: 10.5500/wjt.v7.i6.301] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2017] [Revised: 09/24/2017] [Accepted: 11/22/2017] [Indexed: 02/05/2023] Open
Abstract
In view of the availability of new immunosuppression strategies, the recurrence of allograft glomerulonephritis (GN) are reported to be increasing with time post transplantation. Recent advances in understanding the pathogenesis of the GN recurrent disease provided a better chance to develop new strategies to deal with the GN recurrence. Recurrent GN diseases manifest with a variable course, stubborn behavior, and poor response to therapy. Some types of GN lead to rapid decline of kidney function resulting in a frustrating return to maintenance dialysis. This subgroup of aggressive diseases actually requires intensive efforts to ascertain their pathogenesis so that strategy could be implemented for better allograft survival. Epidemiology of native glomerulonephritis as the cause of end-stage renal failure and subsequent recurrence of individual glomerulonephritis after renal transplantation was evaluated using data from various registries, and pathogenesis of individual glomerulonephritis is discussed. The following review is aimed to define current protocols of the recurrent primary glomerulonephritis therapy.
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Affiliation(s)
- Fedaey Abbas
- Department of Nephrology, Jaber El Ahmed Military Hospital, Safat 13005, Kuwait
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
| | - Mohsen El Kossi
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Doncaster Royal Infirmary, Doncaster DN2 5LT, United Kingdom
| | - Jon Kim Jin
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Nottingham Children Hospital, Nottingham NG7 2UH, United Kingdom
| | - Ajay Sharma
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Royal Liverpool University Hospitals, Liverpool L7 8XP, United Kingdom
| | - Ahmed Halawa
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Department of Transplantation Surgery, Sheffield Teaching Hospitals, Sheffield S5 7AU, United Kingdom
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31
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Wang CS, Gander J, Patzer RE, Greenbaum LA. Mortality and Allograft Loss Trends Among US Pediatric Kidney Transplant Recipients With and Without Focal Segmental Glomerulosclerosis. Am J Kidney Dis 2017; 71:392-398. [PMID: 29277509 DOI: 10.1053/j.ajkd.2017.09.025] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Accepted: 09/30/2017] [Indexed: 12/27/2022]
Abstract
BACKGROUND Pediatric patients with focal segmental glomerulosclerosis (FSGS) have high rates of disease recurrence and allograft failure after kidney transplantation, but there are few data for long-term survival posttransplantation. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS 12,303 pediatric patients (aged <18 years), including 1,408 (11%) patients with FSGS, who received a first kidney transplant in 1990 through 2009 and were followed up through June 2015 were identified from the US Renal Data System database. PREDICTORS Primary cause of end-stage renal disease, FSGS or other. OUTCOMES All-cause patient mortality and allograft loss. RESULTS All-cause mortality significantly improved for patients with FSGS who underwent transplantation in the 2000s versus the 1990s (6.72 vs 12.24 deaths/1,000 patient-years; HR, 0.55; 95% CI, 0.39-0.78; P<0.001). Reductions in allograft loss were less dramatic (75.91 vs 89.05 events/1,000 patient-years; HR, 0.85; 95% CI, 0.74-0.98; P=0.02). After adjusting for baseline characteristics at the time of transplantation, patients with FSGS had similar rates of death compared with patients without FSGS (HRs of 0.81 [P=0.6] and 1.06 [P=0.2] among those who underwent transplantation in the 2000s and 1990s, respectively) despite higher rates of allograft loss (HRs of 1.17 [P=0.03] and 1.27 [P<0.001], respectively). Among patients who underwent transplantation in the 2000s, further adjustment for allograft failure as a time-varying covariate demonstrated a lower rate of death among patients with FSGS compared with those without FSGS (HR, 0.70; P=0.02). LIMITATIONS Lack of information about certain risk factors for mortality, including duration of chronic kidney disease; missing data; and potential primary disease misclassification. CONCLUSIONS Survival of pediatric kidney transplant recipients with FSGS improved between the 1990s and 2000s and was similar to that of recipients without FSGS. Interestingly, adjustment for allograft failure showed greater survival for pediatric patients with FSGS who underwent transplantation in the 2000s as compared with others, suggesting that effective interventions to decrease allograft loss due to disease recurrence may improve patient survival.
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Affiliation(s)
- Chia-Shi Wang
- Division of Pediatric Nephrology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA; Children's Healthcare of Atlanta, Atlanta, GA.
| | - Jennifer Gander
- Division of Transplantation, Department of Surgery, Emory University School of Medicine, Atlanta, GA
| | - Rachel E Patzer
- Division of Transplantation, Department of Surgery, Emory University School of Medicine, Atlanta, GA; Department of Epidemiology, Rollins School of Public Health, Emory University School of Medicine, Atlanta, GA
| | - Larry A Greenbaum
- Division of Pediatric Nephrology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA; Children's Healthcare of Atlanta, Atlanta, GA
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Multiple Targets for Novel Therapy of FSGS Associated with Circulating Permeability Factor. BIOMED RESEARCH INTERNATIONAL 2017; 2017:6232616. [PMID: 28951873 PMCID: PMC5603123 DOI: 10.1155/2017/6232616] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Revised: 05/10/2017] [Accepted: 06/15/2017] [Indexed: 01/13/2023]
Abstract
A plasma component is responsible for altered glomerular permeability in patients with focal segmental glomerulosclerosis. Evidence includes recurrence after renal transplantation, remission after plasmapheresis, proteinuria in infants of affected mothers, transfer of proteinuria to experimental animals, and impaired glomerular permeability after exposure to patient plasma. Therapy may include decreasing synthesis of the injurious agent, removing or blocking its interaction with cells, or blocking signaling or enhancing cell defenses to restore the permeability barrier and prevent progression. Agents that may prevent the synthesis of the permeability factor include cytotoxic agents or aggressive chemotherapy. Extracorporeal therapies include plasmapheresis, immunoadsorption with protein A or anti-immunoglobulin, or lipopheresis. Oral or intravenous galactose also decreases Palb activity. Studies of glomeruli have shown that several strategies prevent the action of FSGS sera. These include blocking receptor-ligand interactions, modulating cell reactions using indomethacin or eicosanoids 20-HETE or 8,9-EET, and enhancing cytoskeleton and protein interactions using calcineurin inhibitors, glucocorticoids, or rituximab. We have identified cardiotrophin-like cytokine factor 1 (CLCF-1) as a candidate for the permeability factor. Therapies specific to CLCF-1 include potential use of cytokine receptor-like factor (CRLF-1) and inhibition of Janus kinase 2. Combined therapy using multiple modalities offers therapy to reverse proteinuria and prevent scarring.
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Rituximab for Recurrence of Primary Focal Segmental Glomerulosclerosis After Kidney Transplantation: Clinical Outcomes. Transplantation 2017; 101:649-656. [PMID: 27043407 DOI: 10.1097/tp.0000000000001160] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Rituximab has shown encouraging results for the treatment of kidney transplantation recipients with focal segmental glomerulosclerosis (FSGS) recurrence. However, the correct, opportune, and safe use of rituximab for this indication remains to be determined. METHODS This multicenter retrospective study reports on 19 new cases aged 35 (15-66) years who developed FSGS recurrence at 12 (1.5-27) days posttransplantation. Initial treatment consisted of plasma exchanges (PE), high doses of calcineurin inhibitors, and steroids. Rituximab was introduced either immediately (N = 6) or after failure of the initial treatment (N = 10) or failed attempted weaning from PE (N = 3). RESULTS Overall, we observed 9 of 19 complete remissions and 3 of 19 partial remissions. Estimated glomerular filtration rates (Modification of Diet in Renal Disease 4) were significantly higher in the responding patients than in nonresponding patients at month (M)12, M36, and M60. Overall, kidney survival at 5 years was 77.4% (95% range, 41.9-92.7). The 5-year graft survival rates in the responding patients and the nonresponding patients were 100% and 36.5%, respectively (P = 0.01). A further course of rituximab was required for 4 patients as a result of FSGS relapse, with good results. During the first year after renal transplantation, 14 patients developed severe infections (16 bacterial, 4 viral, 1 parasitic). CONCLUSIONS In kidney transplantation recipients with recurrent FSGS, rituximab therapy may be a recommended treatment for cases that have failed either the initial treatment or weaning from PE.
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Beaudreuil S, Lorenzo HK, Elias M, Nnang Obada E, Charpentier B, Durrbach A. Optimal management of primary focal segmental glomerulosclerosis in adults. Int J Nephrol Renovasc Dis 2017; 10:97-107. [PMID: 28546764 PMCID: PMC5436760 DOI: 10.2147/ijnrd.s126844] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Focal segmental glomerulosclerosis (FSGS) is a frequent glomerular kidney disease that is revealed by proteinuria or even nephrotic syndrome. A diagnosis can be established from a kidney biopsy that shows focal and segmental glomerulosclerosis. This histopathological lesion may be caused by a primary podocyte injury (idiopathic FSGS) but is also associated with other pathologies (secondary FSGS). The first-line treatment for idiopathic FSGS with nephrotic syndrome is a prolonged course of corticosteroids. However, steroid resistance or steroid dependence is frequent, and despite intensified immunosuppressive treatment, FSGS can lead to end-stage renal failure. In addition, in some cases, FSGS can recur on a graft after kidney transplantation: an unidentified circulating factor may be implicated. Understanding of its physiopathology is unclear, and it remains an important challenge for the scientific community to identify a specific diagnostic biomarker and to develop specific therapeutics. This study reviews the treatment of primary FSGS and the recurrence of FSGS after kidney transplantation in adults.
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Affiliation(s)
- Séverine Beaudreuil
- Department of Nephrology Dialysis Transplantation, Paris-Sud University Hospital, Le Kremlin Bicêtre.,INSERM Unit 1197, Paris-Sud University Hospital, Villejuif, France
| | - Hans Kristian Lorenzo
- Department of Nephrology Dialysis Transplantation, Paris-Sud University Hospital, Le Kremlin Bicêtre.,INSERM Unit 1197, Paris-Sud University Hospital, Villejuif, France
| | - Michele Elias
- Department of Nephrology Dialysis Transplantation, Paris-Sud University Hospital, Le Kremlin Bicêtre
| | - Erika Nnang Obada
- Department of Nephrology Dialysis Transplantation, Paris-Sud University Hospital, Le Kremlin Bicêtre
| | - Bernard Charpentier
- Department of Nephrology Dialysis Transplantation, Paris-Sud University Hospital, Le Kremlin Bicêtre.,INSERM Unit 1197, Paris-Sud University Hospital, Villejuif, France
| | - Antoine Durrbach
- Department of Nephrology Dialysis Transplantation, Paris-Sud University Hospital, Le Kremlin Bicêtre.,INSERM Unit 1197, Paris-Sud University Hospital, Villejuif, France
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Schwartz J, Padmanabhan A, Aqui N, Balogun RA, Connelly-Smith L, Delaney M, Dunbar NM, Witt V, Wu Y, Shaz BH. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue. J Clin Apher 2017; 31:149-62. [PMID: 27322218 DOI: 10.1002/jca.21470] [Citation(s) in RCA: 287] [Impact Index Per Article: 35.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Joseph Schwartz
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York
| | - Anand Padmanabhan
- Blood Center of Wisconsin, Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Nicole Aqui
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Rasheed A Balogun
- Division of Nephrology, University of Virginia, Charlottesville, Virginia
| | - Laura Connelly-Smith
- Department of Medicine, Seattle Cancer Care Alliance and University of Washington, Seattle, Washington
| | - Meghan Delaney
- Bloodworks Northwest, Department of Laboratory Medicine, University of Washington, Seattle, Washington
| | - Nancy M Dunbar
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | - Volker Witt
- Department for Pediatrics, St. Anna Kinderspital, Medical University of Vienna, Vienna, Austria
| | - Yanyun Wu
- Bloodworks Northwest, Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut
| | - Beth H Shaz
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.,New York Blood Center, Department of Pathology.,Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia
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Bambauer R, Latza R, Burgard D, Schiel R. Therapeutic Apheresis in Immunologic Renal and Neurological Diseases. Ther Apher Dial 2017; 21:6-21. [PMID: 28078733 DOI: 10.1111/1744-9987.12499] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2016] [Accepted: 08/17/2016] [Indexed: 12/18/2022]
Abstract
Since the mid 1970s, when membrane modules became available, plasma separation techniques have gained in importance especially in the past few years. The advantages of this method are a complete separation of the corpuscular components from the plasma and due to increased blood flow rate and higher efficacy. Systemic autoimmune diseases based on an immune pathogenesis produce autoantibodies and circulating immune complexes, which cause inflammation in the tissues of various organs. In most cases, these diseases have a poor prognosis without treatment. Therapeutic apheresis (TA) in combination with immunosuppressive therapies has led to a steady increase in survival rates over the last 40 years. The updated information on immunology and molecular biology of different immunologic diseases are discussed in relation to the rationale for apheresis therapy and its place in combination with other modern treatments. The different diseases can be treated by various apheresis methods such as therapeutic plasma exchange (TPE) with substitution solution, or with online plasma or blood purification using adsorption columns, which contain biological or non-biological agents. Here, the authors provide an overview of the most important pathogenic aspects indicating that TA can be a supportive therapy in systemic autoimmune diseases such as renal and neurological disorders. For the immunological diseases that can be treated with TA, the guidelines of the German Working Group of Clinical Nephrology and of the Apheresis Committee of the American Society for Apheresis are cited.
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Affiliation(s)
- Rolf Bambauer
- Formerly: Institute for Blood Purification, Homburg, Germany
| | | | | | - Ralf Schiel
- Inselklinik Heringsdorf GmbH, Seeheilbad Heringsdorf, Germany
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Francis A, Trnka P, McTaggart SJ. Long-Term Outcome of Kidney Transplantation in Recipients with Focal Segmental Glomerulosclerosis. Clin J Am Soc Nephrol 2016; 11:2041-2046. [PMID: 27797890 PMCID: PMC5108191 DOI: 10.2215/cjn.03060316] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Accepted: 07/22/2016] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND OBJECTIVES FSGS can recur after kidney transplantation and is associated with poor graft outcomes. We aimed to assess the incidence of FSGS recurrence post-transplant and determine the effect of graft source on recurrence and graft survival in patients with biopsy-proven FSGS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Using the Australian and New Zealand Dialysis and Transplant Registry, we assessed incidence of FSGS, the influence of donor type on the risk of FSGS recurrence, and graft loss in recipients with ESRD caused by primary FSGS using Kaplan-Meier and logistic regression analyses. RESULTS Between 1992 and 2011, 736 first kidney transplants were performed in 666 adults and 70 children (≤20 years old) with biopsy-proven primary FSGS. FSGS recurred in 76 (10.3%) patients. Younger age (P<0.001), nonwhite ethnicity (P=0.02), and having a live donor (P=0.02) were independent risk factors associated with recurrence. Median graft survival was significantly better for live donor compared with deceased donor grafts (14.8 versus 12.1 years; P<0.01). Disease recurrence predicted poor graft outcomes, with 52% (95% confidence interval, 40% to 63%) 5-year graft survival in the recurrence group compared with 83% (95% confidence interval, 79% to 86%) in the group without recurrent disease (P<0.001). CONCLUSIONS FSGS recurrence after kidney transplantation was more common in live donor kidneys. Despite this, graft survival in live donor recipients was significantly better for both children and adults with FSGS. We propose that live donor transplantation should not be avoided in patients with FSGS.
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Affiliation(s)
- Anna Francis
- Child and Adolescent Renal Service, Lady Cilento Children's Hospital, Brisbane, Queensland, Australia; and
- School of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Peter Trnka
- Child and Adolescent Renal Service, Lady Cilento Children's Hospital, Brisbane, Queensland, Australia; and
- School of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Steven J McTaggart
- Child and Adolescent Renal Service, Lady Cilento Children's Hospital, Brisbane, Queensland, Australia; and
- School of Medicine, University of Queensland, Brisbane, Queensland, Australia
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Acute Disseminated Encephalomyelitis. J Clin Apher 2016; 31:163-202. [PMID: 27322219 DOI: 10.1002/jca.21474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Recurrence and Treatment after Renal Transplantation in Children with FSGS. BIOMED RESEARCH INTERNATIONAL 2016; 2016:6832971. [PMID: 27213154 PMCID: PMC4860214 DOI: 10.1155/2016/6832971] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/25/2015] [Revised: 03/14/2016] [Accepted: 04/04/2016] [Indexed: 01/15/2023]
Abstract
Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage renal disease and a common pathologic diagnosis of idiopathic nephrotic syndrome (NS), especially in steroid-resistant cases. FSGS is known to recur after kidney transplantation, frequently followed by graft loss. However, not all patients with FSGS suffer from recurrence after kidney transplantation, and genetic and secondary FSGS have a negligible risk of recurrence. Furthermore, many cases of recurrence achieve remission with the current management of recurrence (intensive plasmapheresis/immunosuppression, including rituximab), and other promising agents are being evaluated. Therefore, a pathologic diagnosis of FSGS itself should not cause postponement of allograft kidney transplantation. For patients with a high risk of recurrence who presented with classical symptoms of NS, that is, severe edema, proteinuria, and hypoalbuminemia, close monitoring of proteinuria is necessary, followed by immediate, intensive treatment for recurrence.
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FSGS Recurrence in Adults after Renal Transplantation. BIOMED RESEARCH INTERNATIONAL 2016; 2016:3295618. [PMID: 27144163 PMCID: PMC4842050 DOI: 10.1155/2016/3295618] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/25/2015] [Accepted: 03/27/2016] [Indexed: 12/18/2022]
Abstract
Recurrence of focal segmental glomerulosclerosis (FSGS) in the allograft occurs in 30–50% of patients, and it is associated with poor renal allograft survival. Major risk factors for recurrence are younger age at diagnosis, rapid progression to end-stage renal disease, white race, and the loss of previous allografts due to recurrence. Recent data support the hypothesis that circulating permeability factors play a crucial role in podocyte injury and progression of FSGS. Due to lack of controlled trials, the management of recurrent FSGS is inconsistent and highly empirical. Prophylactic and perioperative treatment with plasmapheresis and high-dose (intravenous) cyclosporine represent the main cornerstones of immunosuppressive therapy. In recent years, therapy with rituximab has shown promising results. Despite evidence of activation of the renin-angiotensin system (RAS) in recurrent FSGS and its association with progression, only limited data exist on the renoprotective role of RAS blockade in this setting. Further well designed studies are needed on pathogenesis risk factors and therapeutical options in FSGS and its recurrence after transplantation.
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Hjorten R, Anwar Z, Reidy KJ. Long-term Outcomes of Childhood Onset Nephrotic Syndrome. Front Pediatr 2016; 4:53. [PMID: 27252935 PMCID: PMC4879783 DOI: 10.3389/fped.2016.00053] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2015] [Accepted: 05/06/2016] [Indexed: 12/13/2022] Open
Abstract
There are limited studies on long-term outcomes of childhood onset nephrotic syndrome (NS). A majority of children with NS have steroid-sensitive nephrotic syndrome (SSNS). Steroid-resistant nephrotic syndrome (SRNS) is associated with a high risk of developing end-stage renal disease. Biomarkers and analysis of genetic mutations may provide new information for prognosis in SRNS. Frequently relapsing and steroid-dependent NS is associated with long-term complications, including dyslipidemia, cataracts, osteoporosis and fractures, obesity, impaired growth, and infertility. Long-term complications of SSNS are likely to be under-recognized. There remain many gaps in our knowledge of long-term outcomes of childhood NS, and further study is indicated.
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Affiliation(s)
- Rebecca Hjorten
- Pediatrics Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine , Bronx, NY , USA
| | - Zohra Anwar
- Pediatrics Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine , Bronx, NY , USA
| | - Kimberly Jean Reidy
- Pediatrics Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine , Bronx, NY , USA
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Plasma Exchange for the Recurrence of Primary Focal Segmental Glomerulosclerosis in Adult Renal Transplant Recipients: A Meta-Analysis. J Transplant 2015; 2015:639628. [PMID: 26697207 PMCID: PMC4677212 DOI: 10.1155/2015/639628] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2015] [Accepted: 11/16/2015] [Indexed: 01/10/2023] Open
Abstract
Background. Posttransplant recurrence of primary focal segmental glomerulosclerosis (rFSGS) in the form of massive proteinuria is not uncommon and has detrimental consequences on renal allograft survival. A putative circulating permeability factor has been implicated in the pathogenesis leading to widespread use of plasma exchange (PLEX). We reviewed published studies to assess the role of PLEX on treatment of rFSGS in adults. Methods. Eligible manuscripts compared PLEX or variants with conventional care for inducing proteinuria remission (PR) in rFSGS and were identified through MEDLINE and reference lists. Data were abstracted in parallel by two reviewers. Results. We detected 6 nonrandomized studies with 117 cases enrolled. In a random effects model, the pooled risk ratio for the composite endpoint of partial or complete PR was 0,38 in favour of PLEX (95% CI: 0,23–0,61). No statistical heterogeneity was observed among included studies (I2 = 0%, p = 0,42). On average, 9–26 PLEX sessions were performed to achieve PR. Renal allograft loss due to recurrence was lower (range: 0%–67%) in patients treated with PLEX. Conclusion. Notwithstanding the inherent limitations of small, observational trials, PLEX appears to be effective for PR in rFSGS. Additional research is needed to further elucidate its optimal use and impact on long-term allograft survival.
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Akl AI, Adel H, Rahim MA, Wafa EW, Shokeir AA. Outcome of glomerulonephritis in live-donor renal transplant recipients: A single-centre experience. Arab J Urol 2015; 13:295-305. [PMID: 26609451 PMCID: PMC4656810 DOI: 10.1016/j.aju.2015.09.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Revised: 08/31/2015] [Accepted: 09/03/2015] [Indexed: 11/01/2022] Open
Abstract
OBJECTIVES To investigate the frequency and risk factors affecting the incidence of post-transplantation glomerulonephritis (GN) and the impact of GN on the survival of the graft and the patient. PATIENTS AND METHODS Patients were classified based on histological findings into three groups. Graft survival was ascertained using the Kaplan-Meier method and significance calculated using log-rank tests. For multivariate analysis the Cox model was used. RESULTS Transplant glomerulopathy was the most prevalent glomerular disease in our series followed by recurrent GN and lastly de novo GN. In all, 50% of the de novo GN group had diabetes. The worst graft outcomes were in the recurrent GN group (P = 0.044). Multivariate analysis revealed ageing of the graft and mammalian target of rapamycin (mTOR) immunosuppression as risk factors for development of GN. While, the age of the recipient and donor, anti-lymphocyte globulin induction therapy, and acute rejection were risk factors for poor graft outcomes. CONCLUSIONS GN is an important issue after transplantation. Tracking the incidence and progression of histological findings in the graft may help to guide proper management and improve graft outcome.
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Affiliation(s)
- Ahmed Ibrahim Akl
- Department of Nephrology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
| | - Hany Adel
- Department of Nephrology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
| | - Mona Abdel Rahim
- Department of Pathology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
| | - Ehab Wahba Wafa
- Department of Nephrology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
| | - Ahmed A Shokeir
- Department of Urology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
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Maas RJ, Deegens JK, Wetzels JF. Permeability factors in idiopathic nephrotic syndrome: historical perspectives and lessons for the future. Nephrol Dial Transplant 2015; 29:2207-16. [PMID: 25416821 DOI: 10.1093/ndt/gfu355] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
The term idiopathic nephrotic syndrome (iNS) traditionally covers minimal change disease and primary focal segmental glomerulosclerosis (FSGS), now thought to be separate disease entities. Clinical and experimental evidence suggest that circulating permeability factors are involved in their pathogenesis. In the past four decades, many investigators have searched for the responsible factors, thus far with little success. The recent report of the soluble urokinase plasminogen activator receptor as a causative factor in FSGS has received much attention, but again the initially promising findings were not confirmed. We describe the history of the search for permeability factors, discuss the pitfalls that are likely responsible for the lack of success and propose criteria that should be used in future studies when evaluating candidate permeability factors.
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Affiliation(s)
- Rutger J Maas
- Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Jeroen K Deegens
- Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Jack F Wetzels
- Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
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Lionaki S, Vlachopanos G, Georgalis A, Liapis G, Skalioti C, Zavos G, Boletis JN. Individualized scheme of immunoadsorption for the recurrence of idiopathic focal segmental glomerulosclerosis in the graft: a single center experience. Ren Fail 2015; 37:777-83. [PMID: 25715638 DOI: 10.3109/0886022x.2015.1015366] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
OBJECTIVES To explore the role of immunoadsorption (IA) for the treatment of idiopathic focal segmental glomerulosclerosis (FSGS) recurrence in the renal allograft, if applied in a personalized manner. METHODS We studied patients with end-stage renal disease (ESRD) due to idiopathic FSGS, transplanted between 2001 and 2010. Patients with FSGS recurrence were treated with daily sessions of IA for the first week, followed by an every other day scheme and then individualized tapering until discontinuation. Complete remission was defined as a reduction of 24-h proteinuria to ≤ 0.5 g/day and partial remission as a reduction of 24-h proteinuria to 50% or more from baseline. RESULTS Of the 18 renal transplant recipients with ESRD due to idiopathic FSGS, 12 (66.7%) experienced disease recurrence in a mean time of 0.75 months post-transplantation (KTx), with a mean proteinuria of 8.9 g/day at the time of recurrence. The mean recipient age was 30.8 years; the mean donor age was 47.4 years, while living related donors provided the allograft in seven cases. Four of the patients received therapy with rituximab in addition to IA. During a mean time of follow-up of 48.3 months, seven patients (58.3%) achieved complete remission, and five (41.7%) partial remission. At the end of follow-up, eight patients (66.7%) had functioning grafts, being in sustained remission, in contrast to four patients (33.3%), who ended up in ESRD because of FSGS recurrence. CONCLUSIONS IA was shown efficacious in a small series of patients with recurrent FSGS in the graft. Renal function remained stable in eight of the 12 patients with FSGS recurrence.
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Affiliation(s)
- Sophia Lionaki
- a Department of Nephrology & Transplantation Unit , Laiko Hospital , Athens , Greece
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Paglialonga F, Schmitt CP, Shroff R, Vondrak K, Aufricht C, Watson AR, Ariceta G, Fischbach M, Klaus G, Holtta T, Bakkaloglu SA, Zurowska A, Jankauskiene A, Vande Walle J, Schaefer B, Wright E, Connell R, Edefonti A. Indications, technique, and outcome of therapeutic apheresis in European pediatric nephrology units. Pediatr Nephrol 2015; 30:103-11. [PMID: 25135618 DOI: 10.1007/s00467-014-2907-3] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2014] [Revised: 06/09/2014] [Accepted: 07/08/2014] [Indexed: 11/29/2022]
Abstract
BACKGROUND Few observations on apheresis in pediatric nephrology units have been published. METHODS This retrospective study involved children ≤18 years undergoing plasma exchange (PE), immunoadsorption (IA), or double filtration plasmapheresis (DFPP) in 12 European pediatric nephrology units during 2012. RESULTS Sixty-seven children underwent PE, ten IA, and three DFPP, for a total of 738 PE and 349 IA/DFPP sessions; 67.2 % of PE and 69.2 % of IA/DFPP patients were treated for renal diseases, in particular focal segmental glomerulosclerosis (FSGS), hemolytic-uremic syndrome (HUS), and human leukocyte antigen (HLA) desensitization prior to renal transplantation; 20.9 % of PE and 23.1 % of IA/DFPP patients had neurological diseases. Membrane filtration was the most common technique, albumin the most frequently used substitution fluid, and heparin the preferred anticoagulant. PE achieved full disease remission in 25 patients (37.3 %), partial remission in 22 (32.8 %), and had no effect in 20 (29.9 %). The response to IA/DFPP was complete in seven patients (53.8 %), partial in five (38.5 %), and absent in one (7.7 %). Minor adverse events occurred during 6.9 % of PE and 9.7 % of IA/DFPP sessions. CONCLUSIONS PE, IA, and DFPP are safe apheresis methods in children. Efficacy is high in pediatric patients with recurrent focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (HUS), human leukocyte antigen (HLA) sensitization, and neurological autoimmune diseases.
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Affiliation(s)
- Fabio Paglialonga
- Pediatric Nephrology and Dialysis Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda, 9, 20122, Milan, Italy,
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Reiser J, Nast CC, Alachkar N. Permeability factors in focal and segmental glomerulosclerosis. Adv Chronic Kidney Dis 2014; 21:417-21. [PMID: 25168830 DOI: 10.1053/j.ackd.2014.05.010] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2014] [Revised: 05/30/2014] [Accepted: 05/30/2014] [Indexed: 01/30/2023]
Abstract
Focal and segmental glomerulosclerosis (FSGS) represents a group of glomerular disorders, identified on kidney biopsy, that progress in the histopathologic pattern of sclerosis in parts of some glomeruli. Damage to podocytes usually marks the beginning of the disease, most evident in primary FSGS. In addition to genetic predisposition, there are many acquired causes that disturb normal podocyte homeostasis and allow for the development of FSGS. The aim of this review was to summarize recent findings of the most relevant circulating permeability factors that may serve as biomarkers of active primary idiopathic FSGS and aid in the diagnosis and prediction of recurrent FSGS after kidney transplantation.
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Lee SE, Min SI, Kim YS, Ha J, Ha IS, Cheong HI, Kim SJ, Choi Y, Kang HG. Recurrence of idiopathic focal segmental glomerulosclerosis after kidney transplantation: experience of a Korean tertiary center. Pediatr Transplant 2014; 18:369-76. [PMID: 24802343 DOI: 10.1111/petr.12257] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/24/2014] [Indexed: 11/29/2022]
Abstract
FSGS is the second most common cause of idiopathic NS in children. It often progresses to ESRD and commonly recurs after KT. To investigate the risk factors and the prognosis of recurrence in pediatric idiopathic FSGS in Korea, retrospective review of 43 KT in 38 children with idiopathic FSGS of last two decades was conducted. The patients presented at the median age of 5.1 yr (range 1.1-13.8 yr) and received KT 5.7 yr later (range 1.3-17.6 yr). FSGS recurred in 20 allografts immediately after transplantation, only in those who presented with NS but not in those who presented with AUA. The risk factors for recurrence were age of onset >5 yr and progression to ESRD within six yr but not sooner than 18 months. CR was achieved in 13 patients with FSGS recurrence and sustained in nine without subsequent relapse over a median of six and a half yr (0.6-20.7 yr). Pediatric idiopathic FSGS presenting with NS recurred in more than half of patients after transplantation. Interestingly, more rapid progression within less than 18 months did not predict recurrence. To identify high-risk patients of recurrence, an international cooperative study would be necessary.
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Affiliation(s)
- Se Eun Lee
- Department of Pediatrics, Seoul National University College of Medicine and Research Center for Rare Diseases, Seoul, Korea
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Keith DS. Therapeutic apheresis in renal transplantation; current practices. J Clin Apher 2014; 29:206-10. [DOI: 10.1002/jca.21330] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2014] [Accepted: 05/01/2014] [Indexed: 12/15/2022]
Affiliation(s)
- Douglas S. Keith
- Division of Nephrology; University of Virginia Medical Center; Charlottesville Virginia
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