Recurrent Focal Segmental Glomerulosclerosis Research Articles

A Case of Posttransplant Recurrence of Focal Segmental Glomerulosclerosis with Donor-derived Immunoglobulin A Nephropathy and Banff IIA Acute Cell-mediated Rejection: A Therapeutic Challenge

Primary focal segmental glomerulosclerosis (FSGS) recurrence varies between 10% and 60% and is an important predictor of graft survival. Here, we report the case with a combination of recurrence of FSGS, acute cell-mediated rejection, and donor-derived immunoglobulin A (IgA) nephropathy which required treatment with plasmapheresis and antithymocyte globulin. This patient is an 18-year-old female whose native kidney disease was a biopsy-proven FSGS and underwent ABO compatible live-related renal transplant with her mother as a donor. No induction agents were given and the patient was put on triple immunosuppression with Calcineurin inhibitors (CNIs), Mycophenolate mofetil (MMF), and steroids. On postoperative Day 2, the patient developed nephrotic range proteinuria. A transplant kidney biopsy was done. Biopsy revealed acute cell-mediated rejection, Banff II A with i3, t3, ptc1, v1, and C4d negative. There was also an increase in mesangial cellularity with IgA 3+ and C3 1+ on immunofluorescence which is IgA nephropathy, likely donor derived. Electron microscopy revealed significant effacement of podocytes. CNI levels are adequate. Pulse methylprednisolone 5 doses given. The patient was given two sessions of plasmapheresis with albumin and a single dose of rabbit antithymocyte globulin (ATG) 1.5 mg/kg was given. Plasmapheresis was withheld in view of studies reporting the removal of ATG following plasmapheresis. There was a gradual worsening of renal function with peak serum creatinine of 9 mg/dL which required three sessions of hemodialysis. The second renal biopsy on Day 13 showed features of acute tubular injury with borderline changes suspicious of acute cell mediated rejection (ACMR)–i1, t1. Currently, the patient is on regular follow-up with normal renal function with urine polymerase chain reaction of 0.4. We report this case which presented with a puzzling combination of ACMR, possible recurrence of native disease, and likely donor-derived IgA nephropathy that provided us with challenges in management. Treatment protocols with optimal dosing strategies and assessing response to treatment in these situations are still unclear due to the lack of large randomized trials.

Immediate Recurrence of Genetic Focal Segmental Glomerulosclerosis PostKidney Transplant

Recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation is a serious concern with poor allograft outcomes. Possible circulating permeability factors are postulated as pathogenetic factors leading to recurrence. Genetic FSGS is said to have a negligible risk of posttransplant recurrence. Here, we describe an unfortunate patient of genetic FSGS (pathogenic genetic variant) who had a recurrence within hours after transplant and presented with a sudden onset of anuria. The patient did not respond to plasma exchange and subsequently underwent allograft nephrectomy.

Transplantation: platform to study recurrence of disease.

Beyond the direct benefit that a transplanted organ provides to an individual recipient, the study of the transplant process has the potential to create a better understanding of the pathogenesis, etiology, progression and possible therapy for recurrence of disease after transplantation while at the same time providing insight into the original disease. Specific examples of this include: 1) recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation, 2) recurrent autoimmunity after pancreas transplantation, and 3) recurrence of disease after orthotopic liver transplantation (OLT) for cirrhosis related to progressive steatosis secondary to jejuno-ileal bypass (JIB) surgery. Our team has been studying these phenomena and their immunologic underpinnings, and we suggest that expanding the concept to other pathologic processes and/or transplanted organs that harbor the risk for recurrent disease may provide novel insight into the pathogenesis of a host of other disease processes that lead to organ failure.

Anti-nephrin antibodies in recurrence of focal segmental glomerulosclerosis: closer to discovering the Holy Grail?

Recurrent forms of primary focal segmental glomerulosclerosis (FSGS) pose an unmet challenge to nephrologists, both in terms of understanding the underlying pathophysiology and in terms of identifying an effective management strategy of this disease, which frequently leads to kidney graft loss. In the past few decades, experimental observations both in patients and in animal models have led to the hypothesis of the existence of circulating factors driving the loss of integrity of the glomerular filtration barrier in FSGS. Although different circulating factor candidates have been postulated, none has been unequivocally shown to be pathogenic. In the current study, Shirai etal. propose a new candidate for this role by identifying circulating anti-nephrin autoantibodies in a cohort of patients with post-transplant recurrence of primary FSGS. Recent evidence by Watts etal. has also identified anti-nephrin autoantibodies in the circulation and in the kidney biopsies of patients with minimal change disease. If confirmed, the identification of these autoantibodies would both contribute to identifying the elusive circulating factor in FSGS and increase our understanding of the spectrum of proteinuric glomerular lesions, spanning from minimal change disease to FSGS. The quest for the Holy Grail is perhaps closer to completion.

A multi-institutional study found a possible role of anti-nephrin antibodies in post-transplant focal segmental glomerulosclerosis recurrence

Possible roles of anti-nephrin antibodies in post-transplant recurrent focal segmental glomerulosclerosis (FSGS) have been reported recently. To confirm these preliminary results, we performed a multi-institutional study of 22 Japanese pediatric kidney transplant recipients with FSGS including eight genetic FSGS and 14 non-genetic (presumed primary) FSGS. Eleven of the 14 non-genetic FSGS patients had post-transplant recurrent FSGS. Median (interquartile range) plasma levels of anti-nephrin antibodies in post-transplant recurrent FSGS measured using ELISA were markedly high at 899 (831, 1292) U/mL (cut-off 231 U/mL) before transplantation or during recurrence. Graft biopsies during recurrence showed punctate IgG deposition co-localized with nephrin that had altered localization with increased nephrin tyrosine phosphorylation and Src homology and collagen homology A expressions. Graft biopsies after remission showed no signals for IgG and a normal expression pattern of nephrin. Anti-nephrin antibody levels decreased to 155 (53, 367) U/mL in five patients with samples available after remission. In patients with genetic FSGS as in those with non-genetic FSGS without recurrence, anti-nephrin antibody levels were comparable to those of 30 control individuals, and graft biopsies had no signals for IgG and a normal expression pattern of nephrin. Thus, our results suggest that circulating anti-nephrin antibodies are a possible candidate for circulating factors involved in the pathogenesis of post-transplant recurrent FSGS, and that this may be mediated by nephrin phosphorylation. Larger studies including other ethnicities are required to confirm this finding.

Clinicopathological differences in focal segmental glomerulosclerosis depending on the accompanying pathophysiological conditions in renal allografts

Primary focal segmental glomerulosclerosis (FSGS) is thought to be caused by circulating factors leading to podocytopathy, whereas segmental sclerotic lesions (FSGS lesions) have several causes. We studied the clinicopathological differences of FSGS-lesions in 258 cases of FSGS in renal allografts, depending on the following accompanying pathophysiology: recurrence of primary FSGS, calcineurin inhibitor (CNI)-induced arteriolopathy, antibody-mediated rejection (ABMR), and other conditions. All cases were categorized with the Columbia classification. Recurrent FSGS developed the earliest after transplantation and showed the highest percentage of the collapsing (COL) variant in which collapse of the glomerular capillaries with epithelial hypertrophy was apparent. FSGS accompanying CNI-induced arteriolopathy predominantly developed the not otherwise specified (NOS) variant, showing severe ultrastructural endothelial injury. On the contrary, approximately 7% of the cases showed the COL variant, presenting glomerular endothelial damage such as double contours of glomerular basement membrane and endothelial cell swelling as well as epithelial cell proliferation. FSGS with ABMR had the highest creatinine levels and cellular variant percentage, with marked inflammation and ultrastructural endothelial injury. Approximately two-thirds of the cases without ABMR, CNI-induced arteriopathy, or recurrent FSGS had other coexisting conditions such as glomerulonephritis, T cell-mediated rejection, and reflux nephropathy with progressive tubulointerstitial fibrosis. Most of these cases were of the NOS variant. The clinicopathologic features of post-transplant FSGS differed depending on the associated conditions, and endothelial injury was apparent especially in cases of CNI-induced arteriolopathy and ABMR. Precise observation of FSGS lesions may facilitate the diagnosis and clinical management of FSGS during renal transplantation.

WITHDRAWN: Therapeutic apheresis in renal transplantation: An update

Therapeutic apheresis (TA) plays a significant role in various aspects of renal transplantation. It has been a necessary preconditioning component in ABO incompatible kidney transplants and an important modality in the removal of anti-human leukocyte antigen (HLA) antibodies both in the context of desensitization protocols that have been developed to allow highly sensitized kidney transplant candidates to be successfully transplanted and as treatment of antibody mediated rejection episodes post transplantation. In addition, TA has been used with various results for the management of recurrent focal segmental glomerulosclerosis. The purpose of this review is to examine the evidence supporting the application of TA as an adjunctive therapeutic option to immunosuppressive agents in protocols both before and after kidney transplantation.

Searching for Significance in Oceania: A Voyage of Recurrent FSGS in a Patient from the Marshall Islands with Variants of Uncertain Significance

Searching for Significance in Oceania: A Voyage of Recurrent FSGS in a Patient from the Marshall Islands with Variants of Uncertain Significance

FSGS Recurrence Modeling Using Induced Pluripotent Stem Cell (iPSC)-Derived Podocytes in Patients with Idiopathic Nephrotic Syndrome

FSGS Recurrence Modeling Using Induced Pluripotent Stem Cell (iPSC)-Derived Podocytes in Patients with Idiopathic Nephrotic Syndrome

Incidence, risk factors, and outcomes of recurrent focal segmental glomerulosclerosis in pediatric kidney transplant recipients: A systematic review and meta-analysis.

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. 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. 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). 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.

Current understanding of the molecular mechanisms of circulating permeability factor in focal segmental glomerulosclerosis.

The pathogenetic mechanisms underlying the onset and the post-transplant recurrence of primary focal segmental glomerulosclerosis (FSGS) are complex and remain yet to be fully elucidated. However, a growing body of evidence emphasizes the pivotal role of the immune system in both initiating and perpetuating the disease. Extensive investigations, encompassing both experimental models and patient studies, have implicated T cells, B cells, and complement as crucial actors in the pathogenesis of primary FSGS, with various molecules being proposed as potential "circulating factors" contributing to the disease and its recurrence post kidney-transplantation. In this review, we critically assessed the existing literature to identify essential pathways for a comprehensive characterization of the pathogenesis of FSGS. Recent discoveries have shed further light on the intricate interplay between these mechanisms. We present an overview of the current understanding of the engagement of distinct molecules and immune cells in FSGS pathogenesis while highlighting critical knowledge gaps that require attention. A thorough characterization of these intricate immune mechanisms holds the potential to identify noninvasive biomarkers that can accurately identify patients at high risk of post-transplant recurrence. Such knowledge can pave the way for the development of targeted and personalized therapeutic approaches in the management of FSGS.

The podocyte: glomerular sentinel at the crossroads of innate and adaptive immunity.

Focal segmental glomerulosclerosis (FSGS) is a common glomerular disorder that manifests clinically with the nephrotic syndrome and has a propensity to recur following kidney transplantation. The pathophysiology and therapies available to treat FSGS currently remain elusive. Since the podocyte appears to be the target of apparent circulating factor(s) that lead to recurrence of proteinuria following kidney transplantation, this article is focused on the podocyte. In the context of kidney transplantation, the performance of pre- and post-reperfusion biopsies, and the establishment of in vitro podocyte liquid biopsies/assays allow for the development of clinically relevant studies of podocyte biology. This has given insight into new pathways, involving novel targets in innate and adaptive immunity, such as SMPDL3b, cGAS-STING, and B7-1. Elegant experimental studies suggest that the successful clinical use of rituximab and abatacept, two immunomodulating agents, in our case series, may be due to direct effects on the podocyte, in addition to, or perhaps distinct from their immunosuppressive functions. Thus, tissue biomarker-directed therapy may provide a rational approach to validate the mechanism of disease and allow for the development of new therapeutics for FSGS. This report highlights recent progress in the field and emphasizes the importance of kidney transplantation and recurrent FSGS (rFSGS) as a platform for the study of primary FSGS.

#4635 CIRCULATING NEPHRIN AUTOANTIBODIES IN PATIENTS WITH POST-TRANSPLANT RECURRENCE OF PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS

Abstract Background and Aims Post-transplant recurrence of primary focal segmental glomerulosclerosis (FSGS) is a major challenge in the field of nephrology and kidney transplantation. Primary FSGS is thought to be caused by circulating factors (CFs) that injure podocytes, but these factors remain unknown despite intensive efforts to identify them. Recently, one post-transplant recurrent FSGS patient with pretransplant nephrin autoantibodies was reported (Watts AJB et al, JASN 33:238, 2022). Furthermore, we reported very early post-transplant recurrence changes of podocytes and possible roles of circulating nephrin autoantibodies in a patient with FSGS recurrence (Hattori M et al, AJT 22:2478, 2022). To confirm these preliminary results, we examined the autoantibodies to nephrin and the punctate deposition of IgG colocalized with nephrin using stocked plasma samples and grafted kidney biopsy specimens of the patients with FSGS recurrence. Method This study was approved by the local Ethics Committee of Tokyo Women's Medical University (approval no. 2021-0184). The clinical and research activities reported here are consistent with the Principles of the Declaration of Istanbul as outlined in the “Declaration of Istanbul on Organ Trafficking and Transplant Tourism”. From 1989 to 2022, a total of 78 patients with FSGS underwent kidney transplantation in our institution, and 16 patients experienced post-transplant recurrence of FSGS. Since the stoked plasma samples were available in 14 out of 16 patients, these 14 patients were included in this study. All 14 patients showed immediate post-transplant recurrence and had no pathogenic variants in FSGS-related genes including NPHS1. Circulating anti-nephrin autoantibodies were measured using the ELISA methods based on the Watts's report with one modification, that is, recombinant extracellular domain of human nephrin was obtained commercially (R&D systems, USA). To validate the ELISA system, circulating anti-nephrin autoantibodies were also measured in 9 genetic FSGS patients, 13 membranous nephropathy (MN) patients, 4 lupus nephritis (LN) patients, and 13 healthy controls. Dual immunofluorescence (IF) staining of nephrin and IgG and image acquisition using the two-dimensional structured illumination microscopy mode with a Nikon microscope were performed as previously reported (Hattori M et al, AJT 22:2478, 2022). Results The cut-off level of anti-nephrin antibody calculated from the results of a total 30 cases including 13 MN patients, 4 LN patients, and 13 healthy controls using Frey's formula (J Immunol Method, 1998) was 172.2 U/mL All 14 recurrent patients enrolled in this study had higher titter than the cut-off level and the mean ± SD of the anti-nephrin antibody level in these patients was 939.9 ± 261.8 U/mL. In contrast, the mean anti-nephrin antibody level in patients with genetic FSGS was 98.6 ± 77.3 U/mL, which was comparable with healthy controls. The IF staining of graft biopsy specimens showed punctate depositions of IgG colocalized with nephrin in all 14 recurrent patients. Conclusion The autoantibodies to nephrin in plasma samples and the punctate deposition of IgG colocalized with nephrin in grafted kidney biopsy specimens were observed in all 14 patients with post-transplant recurrent FSGS. Further studies in larger numbers of patients as well as in patients of other ethnicities are clearly required to confirm this surprising result; however, circulating nephrin autoantibodies could be a possible candidate for CFs in the pathogenesis of recurrent FSGS.

Arteriovenous fistula in a renal allograft with gross hematuria and subsequent acute kidney injury due to urinary tract obstruction: a case report

BackgroundArteriovenous fistula (AVF) due to renal allograft biopsy is mechanical trauma resulting from the penetration of small arteries and veins by a core needle. Most AVFs are reported to resolve asymptomatically and spontaneously. This report presents a patient with acute kidney injury (AKI) due to urinary tract obstruction caused by a bleeding AVF in a renal allograft.Case presentationA 22-year-old Japanese woman who underwent living-donor kidney transplantation (KT) at 3 years due to end-stage renal disease caused by focal segmental glomerulosclerosis (FSGS) presented with a renal transplant AVF (gourd-shaped; 42 × 19 × 20 mm). The AVF was unexpectedly discovered by ultrasound before a surveillance biopsy at 10 years after KT. The patient had a history of recurrent FSGS, had undergone several renal allograft biopsies after KT, and did not experience symptoms or growth of the AVF for years. Nineteen years after KT, the patient developed AKI with sudden, asymptomatic, gross hematuria and anuria. Plain computed tomography revealed a hematoma in the pelvis of the renal allograft and bladder tamponade. The AVF was successfully treated by coil embolization. Hemodialysis was performed for AKI, and graft function was gradually recovered.ConclusionsUnexpected bleeding from a renal transplant AVF may lead to transplant dysfunction. Angiographic embolization against the ruptured renal transplant AVF may prevent rebleeding and rescue the renal allograft.

A randomized controlled trial of preemptive rituximab to prevent recurrent focal segmental glomerulosclerosis post-kidney transplant (PRI-VENT FSGS): protocol and study design.

Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease requiring kidney transplantation and can recur in the allograft in 30-80% of recipients resulting in reduced graft survival. Plasmapheresis has shown efficacy in treating some cases of recurrent FSGS but isolated plasmapheresis has not demonstrated efficacy in preventing recurrent FSGS. Rituximab has had anecdotal success in preventing recurrence in a single center study but has not been studied in combination with plasmapheresis for preventing FSGS recurrence. We are conducting a randomized, controlled, multicenter clinical trial of adult and pediatric kidney transplant recipients with primary FSGS to assess whether plasmapheresis in combination with rituximab prevents recurrent disease post-transplantation. Rituximab combined with plasmapheresis is a promising, novel therapy to prevent recurrent FSGS, a disease with limited therapeutic options and no consensus guidelines for prevention or treatment. https://clinicaltrials.gov/ct2/show/NCT03763643, identifier NCT03763643.

A Case of Disseminated Cryptococcus Post-Kidney Transplant

Cryptococcosis is a common invasive fungal infection in solid organ transplant recipients (SOTR) that can be challenging to manage. We discuss a case of disseminated cryptococcosis in a transplant recipient. A 26-year-old woman with a history of ESRD from C1q nephropathy, living-related kidney transplant in early 2012, and allograft nephrectomy in 2015, received a deceased donor kidney transplant (DDKT). Induction after the first transplant was anti-thymocyte globulin (ATG) and maintenance immunosuppression (IS) included tacrolimus (TAC), mycophenolate (MMF), and prednisone. In December 2014, she developed nephrotic range proteinuria due to recurrent FSGS failing plasmapheresis and Intravenous immunoglobulin leading to advanced chronic kidney disease and dialysis dependence. MMF was held due to Cytomegalovirus (CMV) DNAemia. In January 2015, she developed bilateral, painful leg ulcers. Skin biopsy, spinal fluid analysis, and culture were positive for <em>Cryptococcus neoformans.</em> She was treated with liposomal Amphotericin B (LAB) for 3 weeks and 5 doses of flucytosine (5FC) followed by maintenance oral fluconazole with recurrence requiring resumption of LAB and 5FC. The patient underwent a transplant nephrectomy in May 2015 following which IS, LAB, and 5FC were discontinued and maintenance fluconazole initiated. In 2018, another skin biopsy revealed a recurrence. Maintenance antifungal was switched to itraconazole based on fungal isolate minimum inhibitory concentration (MIC) leading to remission that persisted through subsequent DDKT in August 2022. Induction IS was ATG and maintenance included TAC, MMF, and prednisone. The post-transplant course was complicated by delayed graft function requiring dialysis for about three weeks, followed by renal recovery. She continues maintenance of itraconazole under the supervision of a transplant infectious disease specialist and <em>cryptococca</em>l disease remains in remission. IS reduction or complete withdrawal is important in managing disseminated cryptococcosis in SOTR. Management of disseminated disease may require an extended course of LAB, 5FC, and maintenance azole based on MIC.

Incidence and risk factors for recurrent focal segmental glomerulosclerosis after kidney transplantation: a meta-analysis

Aims To systematically review the incidence and risk factors for recurrent FSGS after kidney transplantation. Methods We searched PubMed, Embase, Medline, Web of Science, the Cochrane Library, CNKI, CBMdisc, Wanfang, and Weipu for case-control studies related to recurrent FSGS from the establishment until October 2022. The protocol was registered on PROSPERO (CRD42022315448). Data were analyzed using Stata 12.0, with odds ratios (counting data) and standardized mean difference (continuous data) being considered as effect sizes. If the I 2 value was greater than 50%, the random-effects model was used; otherwise, a fixed-effects model was used. A meta-analysis on the incidence and risk factors for recurrent FSGS after kidney transplantation was performed. Results A total of 22 studies with 966 patients and 12 factors were included in the meta-analysis. There were 358 patients with recurrent FSGS and 608 patients without FSGS after kidney transplantation. The results showed that the recurrence rate of FSGS after kidney transplantation was 38% (95% CI: 31%–44%). Age at transplantation (SMD = −0.47, 95% CI −0.73 to −0.20, p = .001), age at onset (SMD = −0.31, 95% CI −0.54 to −0.08, p = .008), time from diagnosis to kidney failure (SMD = −0.24, 95% CI −0.43 to −0.04, p = .018), proteinuria before KT (SMD = 2.04, 95% CI 0.91 − 3.17, p < .001), related donor (OR 1.99, 95% CI 1.20 − 3.30, p = .007) and nephrectomy of native kidneys (OR 6.53, 95% CI 2.68 − 15.92, p < .001) were associated with recurrent FSGS, whereas HLA mismatches, duration of dialysis before KT, sex, living donor, tacrolimus use and previous transplantation were not associated with recurrent FSGS after kidney transplantation. Conclusions The recurrence of FSGS after kidney transplantation remains high. Clinical decision-making should warrant further consideration of these factors, including age, original disease progression, proteinuria, related donor, and nephrectomy of native kidneys.

Clinical and histopathologic predictors of recurrent glomerulonephritis after kidney transplantation.

We evaluated the long-term outcomes of recurrent glomerulonephritis (RGN) using clinical, histopathological, and demographic predictors. A retrospective cohort study of kidney transplant recipients (KTR) in two renal centers between 2005 and 2020.Clinical and native kidney histological data were analyzed. The risk factors and outcomes of each primary glomerulonephritis subtype were assessed using Cox methods. 336 recipients with primary glomerulonephritis were analyzed. RGN was diagnosed in 17%, 20%, 25%, and 13% of recipients with IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative glomerulonephritis (MPGN), respectively. Median time to recurrence was shortest in FSGS (.6 years IQR .2-2.9) and longest in MN (6.3 years IQR 3.3-8.0) whereas time to graft loss after diagnosis was shortest in MPGN (.3 years IQR .1-1.7) and longest in IgAN (2.9year IQR 1.3-4.3). Recipients with recurrent IgAN were likely to be younger, have higher proteinuria at diagnosis, receive living donor allografts, receive cyclosporine treatment, have a history of acute rejection, and have segmental sclerosis in native glomeruli. Younger age of the donors, higher proteinuria at diagnosis, alemtuzumab, proteinuria within the first 12 months, acute rejection, low baseline eGFR, mesangial proliferation, and IgG and IgA deposits were associated with FSGS recurrence. MPGN recurrence was predicted by lower BMI at transplantation, and crescentic native disease. Death-censored graft survival at 5-, 10-, and 15-years was 83%, 51%, and 29% in the RGN group and 95%, 93%, and 84%, respectively in the non-RGN group. Over 15 years, recipients with RGN are nine times more likely than those without RGN to lose their grafts, regardless of donor type, acute rejection, and baseline eGFR. Transplant recipients of related donor allograft were not more likely to have recurrent GN than non-related donors.

Post-operative recurrence of focal segmental glomerulosclerosis according to pre-transplant treatment after kidney transplantation

BackgroundRecurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation (KT) is a serious complication and a significant risk factor for graft failure. However, there is no clear evidence of the effectiveness of pre-transplant treatment using plasmapheresis (PP) or rituximab in preventing post-operative FSGS recurrence after KT.MethodsThis single-center retrospective study included 99 adult patients with biopsy-proven primary FSGS who underwent KT between 2007 and 2018. The patients were divided into the pre-treatment group (N = 53, 53.5%) and no pre-treatment group (N = 46, 46.5%). In the pre-transplant group, prophylactic PP was administered before KT in patients undergoing living donor transplantation and the day after KT in those undergoing deceased donor transplantation.ResultsThe rate of immediate post-operative recurrence was significantly higher in the no pre-treatment group (16 [34.8%]) than in the pre-treatment group (5 [9.4%]; P = 0.002). There were three cases of graft failure due to recurrent FSGS, all of which were in the no pre-treatment group. After adjusting for possible confounding factors, age (per 10-year increase; OR = 0.61, CI, 0.42–0.90; P = 0.012) and pre-transplant treatment (vs. no pre-transplant treatment; OR = 0.17, CI, 0.05–0.54; P = 0.003) were identified as significant factors associated with FSGS recurrence. The rate of death-censored graft survival was significantly superior in the pretransplant treatment group (P = 0.042).ConclusionPre-transplant treatment with PP was associated with beneficial effects on preventing FSGS recurrence after KT.

Early recurrence of focal segmental glomerulosclerosis in kidney transplant recipients: When to consider regifting

BackgroundLong term outcomes in transplant recipients experiencing recurrent focal segmental glomerulosclerosis (FSGS) remains poor. Despite early treatment, more than half lose their graft. The aims of this study were to evaluate treatment patterns, outcomes and to evaluate for predictors of treatment failure in recurrent FSGS. MethodsThis was a single center retrospective observational study. Between 1/2014 and 8/2019, 1860 kidney transplantations were performed at UCLA, 100 of which had end stage renal disease due to biopsy-proven FSGS. Comparative statistics were obtained and a multivariate analysis for graft outcomes in patients with recurrence was constructed. The primary outcomes were recurrent FSGS, allograft failure and pheresis dependence. ResultsTwenty-six of the 100recipients experienced FSGS recurrence. Patients with recurrence were younger (34.3 vs. 44.9, p = 0.001) and more likely to have had native nephrectomy (27% vs. 3%, p = 0.001). Gender, race, comorbidities, donor type, previous transplants and rates of rejection were similar between the recurrence and non-recurrence groups. Most patients received plasmapheresis (n = 24) with or without rituximab (11 vs. 13) which allowed for recovery of graft function in 18 patients (75%). Those experiencing a complete recovery required a median of 9 pheresis sessions, while those with graft failure (n = 3) or who became plasmapheresis-dependent (n = 5) required a median of 59 and 158 sessions, respectively. A multivariate analysis was constructed and no additional predictors of graft failure were encountered. ConclusionsPatients with recurrent FSGS whoexperienced remissiondid so following a short course of plasmapheresis. The patients whose recurrence never resolved or who lost their graft underwent much longer courses of plasmapheresis. If this pattern of early durable response is validated in larger studies, there may be a future when transplant teams discuss the possibility of re-gifting based on treatment response to plasmapheresis following recurrence.