scholarly journals Novel Diagnostic and Therapeutic Techniques Reveal Changed Metabolic Profiles in Recurrent Focal Segmental Glomerulosclerosis 

2020 ◽  
Author(s):  
Janina Müller-Deile ◽  
George Sarau ◽  
Christoph Daniel ◽  
Christian Jaremenko ◽  
Ahmed M Kotb ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Raman Spectra ◽  
Focal Segmental Glomerulosclerosis ◽  
Disease Recurrence ◽  
Early Recurrence ◽  
Metabolome Analysis ◽  
Novel Technologies ◽  
Filtration Barrier ◽  
Segmental Glomerulosclerosis ◽  
Living Related

Abstract Idiopathic forms of Focal Segmental Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can lead 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. We then performed Raman spectroscopy in the <50 kD 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 metabolom 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.

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

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.

MO247NOVEL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES REVEAL CHANGED METABOLOMIC PROFILE IN RECURRENT FOCAL SEGMENTAL GLOMERULOSCLEROSIS*

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Janina Müller-Deile ◽  
George Sarau ◽  
Ahmed Kotb ◽  
Christoph Daniel ◽  
Stefan Kalkhof ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Raman Spectroscopy ◽  
Kidney Transplantation ◽  
Raman Spectra ◽  
Focal Segmental Glomerulosclerosis ◽  
Disease Recurrence ◽  
Metabolome Analysis ◽  
Novel Technologies ◽  
Filtration Barrier ◽  
Segmental Glomerulosclerosis

Abstract Background and Aims Idiopathic forms of Focal Segmental Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can lead 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 can allow us to study FSGS from a yet unexplored angle. Method We used novel treatment options, a personalized in vitro and in vivo assay as well as Raman spectroscopy and mass spectrometry for recurrent FSGS. Results 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 (Fig. 1). 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 podocyte’s actin cytoskeleton inducing a functional phenotype (Fig. 2, Fig. 3). We then performed Raman spectroscopy in the &lt;50 kD serum fraction (Fig. 4), on cultured podocytes treated with the FSGS serum (Fig. 5), and in kidney biopsies of the same patient at the time of transplantation and at the time of disease recurrence (Fig. 6). The analysis revealed metabolomic changes in podocytes induced by the FSGS serum as well as in focal glomerular and parietal epithelial cell regions in the FSGS biopsy. Several disturbed Raman spectra were identified in the fractionated serum and metabolome analysis by mass spectrometry detected lipid profiles in the FSGS serum, which corresponded to disturbances in the Raman spectra. Conclusion Our novel innovative analysis reveals changed lipid metabolome profiles associated with idiopathic FSGS that might reflect a new subtype of the disease.

scholarly journals Challenges in primary focal segmental glomerulosclerosis diagnosis: from the diagnostic algorithm to novel biomarkers

2020 ◽  
Author(s):  
Conxita Jacobs-Cachá ◽  
Ander Vergara ◽  
Clara García-Carro ◽  
Irene Agraz ◽  
Nestor Toapanta-Gaibor ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Focal Segmental Glomerulosclerosis ◽  
Graft Function ◽  
Experimental Studies ◽  
Diagnostic Algorithm ◽  
Disease Recurrence ◽  
Glomerular Diseases ◽  
Filtration Barrier ◽  
Segmental Glomerulosclerosis ◽  
Stage Renal Disease

Abstract Primary or idiopathic focal segmental glomerulosclerosis (FSGS) is a kidney entity that involves the podocytes, leading to heavy proteinuria and in many cases progresses to end-stage renal disease. Idiopathic FSGS has a bad prognosis, as it involves young individuals who, in a considerably high proportion (∼15%), are resistant to corticosteroids and other immunosuppressive treatments as well. Moreover, the disease recurs in 30–50% of patients after kidney transplantation, leading to graft function impairment. It is suspected that this relapsing disease is caused by a circulating factor(s) that would permeabilize the glomerular filtration barrier. However, the exact pathologic mechanism is an unsettled issue. Besides its poor outcome, a major concern of primary FSGS is the complexity to confirm the diagnosis, as it can be confused with other variants or secondary forms of FSGS and also with other glomerular diseases, such as minimal change disease. New efforts to optimize the diagnostic approach are arising to improve knowledge in well-defined primary FSGS cohorts of patients. Follow-up of properly classified primary FSGS patients will allow risk stratification for predicting the response to different treatments. In this review we will focus on the diagnostic algorithm used in idiopathic FSGS both in native kidneys and in disease recurrence after kidney transplantation. We will emphasize those potential confusing factors as well as their detection and prevention. In addition, we will also provide an overview of ongoing studies that recruit large cohorts of glomerulopathy patients (Nephrotic Syndrome Study Network and Cure Glomerulonephropathy, among others) and the experimental studies performed to find novel reliable biomarkers to detect primary FSGS.

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

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
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.

scholarly journals UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant

2021 ◽  
Author(s):  
Ben C. Reynolds ◽  
Angela Lamb ◽  
Caroline A. Jones ◽  
Pallavi Yadav ◽  
Kay S. Tyerman ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Function ◽  
Focal Segmental Glomerulosclerosis ◽  
Graft Function ◽  
Case Series ◽  
Disease Recurrence ◽  
Post Transplantation ◽  
Segmental Glomerulosclerosis ◽  
Kidney Replacement Therapy ◽  
Risk Of Disease

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.

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

2020 ◽  
Author(s):  
Thomas Mühlbacher ◽  
Kerstin Amann ◽  
Moritz Mahling ◽  
Silvio Nadalin ◽  
Nils Heyne ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Focal Segmental Glomerulosclerosis ◽  
Costimulation Blockade ◽  
Segmental Glomerulosclerosis ◽  
Remission Maintenance ◽  
Maintenance Immunosuppression ◽  
Therapeutic Concepts ◽  
Allograft Outcome

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

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