Apolipoprotein A-Ib as a biomarker of focal segmental glomerulosclerosis recurrence after kidney transplantation: diagnostic performance and assessment of its prognostic value - a multi-centre cohort study

A major complication of primary focal segmental glomerulosclerosis (FSGS) is its recurrence after kidney transplantation that happens in 30 to 40% of the patients. The diagnosis of these relapses is not always easy as the histological lesions are not highly specific and appear after the proteinuria increase. Currently, there are no accurate biomarkers to detect FSGS recurrence. Our group identified a modified form of Apolipoprotein A-I (ApoA-I), named ApoA-Ib, specifically present in the urine of recurrent FSGS patients after kidney transplantation. Aberrant forms of ApoA-I have also been described in the urine of native primary FSGS patients; this feature has been associated with prominent staining of ApoA-I at the apical membrane of the tubular cells. In this study, we aim to analyze the ApoA-I distribution in kidney allograft biopsies of recurrent FSGS patients. We detected ApoA-I by immunohistochemistry in kidney allograft biopsies of patients with FSGS relapse after kidney transplantation and in kidney allograft biopsies of patients with a disease different from FSGS in the native kidney (non-FSGS). In recurrent FSGS patients, ApoA-I was prominently localized at the brush border of the tubular cells, while in the non-FSGS patients, ApoA-I was found along the cytoplasm of the tubular cells. The localization of ApoA-I at the brush border of the tubular cells is a specific feature of primary FSGS in relapse. This suggests that ApoA-I staining in kidney biopsies, coupled with ApoA-Ib measurement in urine, could be used as a diagnostic tool of primary FSGS relapse after kidney transplantation due to its highly specific tubular distribution.

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Treatment outcomes of recurrent primary focal segmental glomerulosclerosis (FSGS) after kidney transplantation

10.26226/morressier.5a38ffa2d462b8029238b706 ◽

2018 ◽

Author(s):

Rute Aguiar

Keyword(s):

Kidney Transplantation ◽

Treatment Outcomes ◽

Focal Segmental Glomerulosclerosis ◽

Segmental Glomerulosclerosis

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

Clinical Kidney Journal ◽

10.1093/ckj/sfaa267 ◽

2020 ◽

Author(s):

Thomas Mühlbacher ◽

Kerstin Amann ◽

Moritz Mahling ◽

Silvio Nadalin ◽

Nils Heyne ◽

...

Keyword(s):

Kidney Transplantation ◽

Focal Segmental Glomerulosclerosis ◽

Costimulation Blockade ◽

Segmental Glomerulosclerosis ◽

Remission Maintenance ◽

Maintenance Immunosuppression ◽

Therapeutic Concepts ◽

Allograft Outcome

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

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Rituximab for recurrence of primary focal segmental glomerulosclerosis after kidney transplantation: Results of a nationwide study

American Journal of Transplantation ◽

10.1111/ajt.16504 ◽

2021 ◽

Author(s):

Camille Lanaret ◽

Dany Anglicheau ◽

Vincent Audard ◽

Mathias Büchler ◽

Sophie Caillard ◽

...

Keyword(s):

Kidney Transplantation ◽

Focal Segmental Glomerulosclerosis ◽

Nationwide Study ◽

Segmental Glomerulosclerosis

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Novel diagnostic and therapeutic techniques reveal changed metabolic profiles in recurrent focal segmental glomerulosclerosis

Scientific Reports ◽

10.1038/s41598-021-83883-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Janina Müller-Deile ◽

George Sarau ◽

Ahmed M. Kotb ◽

Christian Jaremenko ◽

Ulrike E. Rolle-Kampczyk ◽

...

Keyword(s):

Kidney Transplantation ◽

Raman Spectra ◽

Focal Segmental Glomerulosclerosis ◽

Disease Recurrence ◽

Early Recurrence ◽

Metabolome Analysis ◽

Novel Technologies ◽

Filtration Barrier ◽

Segmental Glomerulosclerosis ◽

Living Related

AbstractIdiopathic forms of Focal Segmental Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can lead to early recurrence of FSGS and kidney failure after kidney transplantation. In the past three decades, many research endeavors were undertaken to identify these unknown factors. Even though some potential candidates have been recently discussed in the literature, “the” actual factor remains elusive. Therefore, there is an increased demand in FSGS research for the use of novel technologies that allow us to study FSGS from a yet unexplored angle. Here, we report the successful treatment of recurrent FSGS in a patient after living-related kidney transplantation by removal of circulating factors with CytoSorb apheresis. Interestingly, the classical published circulating factors were all in normal range in this patient but early disease recurrence in the transplant kidney and immediate response to CytoSorb apheresis were still suggestive for pathogenic circulating factors. To proof the functional effects of the patient’s serum on podocytes and the glomerular filtration barrier we used a podocyte cell culture model and a proteinuria model in zebrafish to detect pathogenic effects on the podocytes actin cytoskeleton inducing a functional phenotype and podocyte effacement. We then performed Raman spectroscopy in the < 50 kDa serum fraction, on cultured podocytes treated with the FSGS serum and in kidney biopsies of the same patient at the time of transplantation and at the time of disease recurrence. The analysis revealed changes in podocyte metabolome induced by the FSGS serum as well as in focal glomerular and parietal epithelial cell regions in the FSGS biopsy. Several altered Raman spectra were identified in the fractionated serum and metabolome analysis by mass spectrometry detected lipid profiles in the FSGS serum, which were supported by disturbances in the Raman spectra. Our novel innovative analysis reveals changed lipid metabolome profiles associated with idiopathic FSGS that might reflect a new subtype of the disease.

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A Form of Apolipoprotein A-I Is Found Specifically in Relapses of Focal Segmental Glomerulosclerosis Following Transplantation

American Journal of Transplantation ◽

10.1111/j.1600-6143.2012.04338.x ◽

2012 ◽

Vol 13 (2) ◽

pp. 493-500 ◽

Cited By ~ 27

Author(s):

J. Lopez-Hellin ◽

C. Cantarell ◽

L. Jimeno ◽

A. Sanchez-Fructuoso ◽

N. Puig-Gay ◽

...

Keyword(s):

Focal Segmental Glomerulosclerosis ◽

Apolipoprotein A ◽

Segmental Glomerulosclerosis

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Preoperative Low-Density Lipoprotein Apheresis for Preventing Recurrence of Focal Segmental Glomerulosclerosis after Kidney Transplantation

Journal of Transplantation ◽

10.1155/2018/8926786 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Akihito Sannomiya ◽

Toru Murakami ◽

Ichiro Koyama ◽

Kosaku Nitta ◽

Ichiro Nakajima ◽

...

Keyword(s):

Renal Failure ◽

Kidney Transplantation ◽

Focal Segmental Glomerulosclerosis ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Ldl Apheresis ◽

Segmental Glomerulosclerosis ◽

Living Related ◽

Observation Period

Background. Focal segmental glomerulosclerosis (FSGS) often develops rapidly and frequently progresses to renal failure, while the recurrence rate after kidney transplantation is 20–50%. We performed low-density lipoprotein (LDL) apheresis before kidney transplantation in FSGS patients to prevent recurrence. Methods. Five adult patients with chronic renal failure due to FSGS undergoing living related donor kidney transplantation were investigated retrospectively. LDL apheresis was done 1-2 times before transplantation. Postoperative renal function and recurrence of FSGS were assessed. Results. The patients were two men and three women aged 24 to 41 years. The observation period ranged from 60 days to 22 months. Preoperative LDL apheresis was performed once in one patient and twice in four patients. Blood LDL cholesterol levels were normal before LDL apheresis and remained normal both after LDL apheresis and after kidney transplantation. Additional LDL apheresis was performed once in one patient with mild proteinuria after transplantation. The renal graft survived in all patients and there was no evidence of recurrent FSGS. Conclusions. Although the observation period was short, FSGS did not recur in all 5 patients receiving preoperative LDL apheresis. These results suggest that LDL apheresis can be effective in preventing recurrence of FSGS after kidney transplantation.

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