Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1093/ndt/gfab104.005
Titel (primär) Novel diagnostic and therapeutic techniques reveal changed metabolomic profile in recurrent focal segmental glomerulosclerosis
Autor Müller-Deile, J.; Sarau, G.; Kotb, A.; Daniel, C.; Kalkhof, S.; Christiansen, S.; Schiffer, M.
Quelle Nephrology Dialysis Transplantation
Erscheinungsjahr 2021
Department MOLSYB
Band/Volume 36
Heft Suppl. 1
Seite von art. 7286
Sprache englisch
Topic T9 Healthy Planet
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 <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.

dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=25406
Müller-Deile, J., Sarau, G., Kotb, A., Daniel, C., Kalkhof, S., Christiansen, S., Schiffer, M. (2021):
Novel diagnostic and therapeutic techniques reveal changed metabolomic profile in recurrent focal segmental glomerulosclerosis
Nephrol. Dial. Transplant. 36 (Suppl. 1), art. 7286 10.1093/ndt/gfab104.005