Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May 18;10(10):2174.
doi: 10.3390/jcm10102174.

A Specific Tubular ApoA-I Distribution Is Associated to FSGS Recurrence after Kidney Transplantation

Conxita Jacobs-Cachá  1 , Natàlia Puig-Gay  2 , Ander Vergara  1 , Maria-Alejandra Gabaldon  3 , Joana Sellarés  1 , Yolanda Villena-Ortiz  2 , Irene Agraz  1 , Francesc Moreso  1   4 , Maria José Soler  1 , Daniel Serón  1   4 , Joan López-Hellín  2
Affiliations

A Specific Tubular ApoA-I Distribution Is Associated to FSGS Recurrence after Kidney Transplantation

Conxita Jacobs-Cachá et al. J Clin Med. .

Abstract

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.

Keywords: ApoA-I; ApoA-Ib; FSGS; apolipoprotein A-I; apolipoprotein A-Ib; biomarkers; focal segmental glomerulosclerosis; glomerular disease; kidney transplantation; recurrence.

PubMed Disclaimer

Conflict of interest statement

C.J.-C declares travel support from Travere Therapeutics, outside of this work. A.V. reports personal fees and non-financial support from Mundipharma, outside this work. M.J.S. reports personal fees from NovoNordisk, Jansen, Mundipharma, AstraZeneca, Esteve, Fresenius, Ingelheim Lilly, Vifor, ICU and grants and personal fees from Boehringer, outside of this work. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Glomerular ApoA-I staining in recurrent FSGS patients and non-FSGS patients. ApoA-I was detected by immunohistochemistry in kidney allograft biopsies of recurrent FSGS patients and non-FSGS patients. Images were taken at 40× magnification and a representative picture of the ApoA-I staining obtained in the glomerular compartment of each patient is shown. No differences in the glomerular ApoA-I staining were found between recurrent-FSGS and non-FSGS patients.
Figure 2
Figure 2
ApoA-I is located at the brush border of the tubular cells in FSGS recurrent patients. ApoA-I was detected by immunohistochemistry in kidney allograft biopsies of recurrent FSGS patients and non-FSGS patients. Images were taken at 40× magnification and a representative picture of the ApoA-I staining obtained in the tubular section of each patient is shown. In the tubular cells, ApoA-I was specifically found in the apical membrane of the tubular cells (brush border) in recurrent FSGS patients (arrows), while non-FSGS patients showed a vesicular ApoA-I staining pattern (asterisk).
Figure 3
Figure 3
Localization of ApoA-I and megalin, a specific marker of the proximal tubular brush border, in recurrent FSGS and non-FSGS kidney allograft biopsies. ApoA-I and megalin were detected in kidney allograft biopsies by immunofluorescence using specific antibodies and nuclei were counterstained with Hoechst 33342. The figure shows a representative image of the megalin (in green), ApoA-I (in red) and Hoechst (in blue) staining obtained in recurrent-FSGS and non-FSGS patients; as well as the merged image. Megalin staining (in green) localized at the brush border of the proximal tubular cells in both recurrent FSGS and non-FSGS patients. Regarding ApoA-I, relapsing FSGS patients showed a strong ApoA-I-megalin colocalization, which was not observed in non-FSGS patients (see details of each case in the merged image zoom box).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Ponticelli C. Recurrence of focal segmental glomerular sclerosis (FSGS) after renal transplantation. Nephrol. Dial. Transplant. 2010;25:25–31. doi: 10.1093/ndt/gfp538. - DOI - PubMed
    1. Rosenberg A.Z., Kopp J.B. Focal Segmental Glomerulosclerosis. Clin. J. Am. Soc. Nephrol. 2017;12:502–517. doi: 10.2215/CJN.05960616. - DOI - PMC - PubMed
    1. Sprangers B., Kuypers D.R. Recurrence of glomerulonephritis after renal transplantation. Transplant. Rev. 2013;27:126–134. doi: 10.1016/j.trre.2013.07.004. - DOI - PubMed
    1. Lopez-Hellin J., Cantarell C., Jimeno L., Sanchez-Fructuoso A., Puig-Gay N., Guirado L., Vilariño N., Gonzalez-Roncero F.M., Mazuecos A., Lauzurica R., et al. A form of apolipoprotein a-I is found specifically in relapses of focal segmental glomerulosclerosis following transplantation. Am. J. Transplant. 2013;13:493–500. doi: 10.1111/j.1600-6143.2012.04338.x. - DOI - PubMed
    1. Puig-Gay N., Jacobs-Cacha C., Sellarès J., Guirado L., González Roncero F., Jiménez C., Zárraga S., Paul J., Lauzurica R., Alonso Á., et al. 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. Transpl. Int. 2019;32:313–322. doi: 10.1111/tri.13372. - DOI - PubMed

LinkOut - more resources