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Ultrastructural Characterization of Proteinuric Patients Predicts Clinical Outcomes.

Publication ,  Journal Article
Royal, V; Zee, J; Liu, Q; Avila-Casado, C; Smith, AR; Liu, G; Mariani, LH; Hewitt, S; Holzman, LB; Gillespie, BW; Hodgin, JB; Barisoni, L
Published in: J Am Soc Nephrol
April 2020

BACKGROUND: The analysis and reporting of glomerular features ascertained by electron microscopy are limited to few parameters with minimal predictive value, despite some contributions to disease diagnoses. METHODS: We investigated the prognostic value of 12 electron microscopy histologic and ultrastructural changes (descriptors) from the Nephrotic Syndrome Study Network (NEPTUNE) Digital Pathology Scoring System. Study pathologists scored 12 descriptors in NEPTUNE renal biopsies from 242 patients with minimal change disease or FSGS, with duplicate readings to evaluate reproducibility. We performed consensus clustering of patients to identify unique electron microscopy profiles. For both individual descriptors and clusters, we used Cox regression models to assess associations with time from biopsy to proteinuria remission and time to a composite progression outcome (≥40% decline in eGFR, with eGFR<60 ml/min per 1.73 m2, or ESKD), and linear mixed models for longitudinal eGFR measures. RESULTS: Intrarater and interrater reproducibility was >0.60 for 12 out of 12 and seven out of 12 descriptors, respectively. Individual podocyte descriptors such as effacement and microvillous transformation were associated with complete remission, whereas endothelial cell and glomerular basement membrane abnormalities were associated with progression. We identified six descriptor-based clusters with distinct electron microscopy profiles and clinical outcomes. Patients in a cluster with more prominent foot process effacement and microvillous transformation had the highest rates of complete proteinuria remission, whereas patients in clusters with extensive loss of primary processes and endothelial cell damage had the highest rates of the composite progression outcome. CONCLUSIONS: Systematic analysis of electron microscopic findings reveals clusters of findings associated with either proteinuria remission or disease progression.

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Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

April 2020

Volume

31

Issue

4

Start / End Page

841 / 854

Location

United States

Related Subject Headings

  • Young Adult
  • Urology & Nephrology
  • Reproducibility of Results
  • Proteinuria
  • Prognosis
  • Predictive Value of Tests
  • Podocytes
  • Nephrosis, Lipoid
  • Microscopy, Electron
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Royal, V., Zee, J., Liu, Q., Avila-Casado, C., Smith, A. R., Liu, G., … Barisoni, L. (2020). Ultrastructural Characterization of Proteinuric Patients Predicts Clinical Outcomes. J Am Soc Nephrol, 31(4), 841–854. https://doi.org/10.1681/ASN.2019080825
Royal, Virginie, Jarcy Zee, Qian Liu, Carmen Avila-Casado, Abigail R. Smith, Gang Liu, Laura H. Mariani, et al. “Ultrastructural Characterization of Proteinuric Patients Predicts Clinical Outcomes.J Am Soc Nephrol 31, no. 4 (April 2020): 841–54. https://doi.org/10.1681/ASN.2019080825.
Royal V, Zee J, Liu Q, Avila-Casado C, Smith AR, Liu G, et al. Ultrastructural Characterization of Proteinuric Patients Predicts Clinical Outcomes. J Am Soc Nephrol. 2020 Apr;31(4):841–54.
Royal, Virginie, et al. “Ultrastructural Characterization of Proteinuric Patients Predicts Clinical Outcomes.J Am Soc Nephrol, vol. 31, no. 4, Apr. 2020, pp. 841–54. Pubmed, doi:10.1681/ASN.2019080825.
Royal V, Zee J, Liu Q, Avila-Casado C, Smith AR, Liu G, Mariani LH, Hewitt S, Holzman LB, Gillespie BW, Hodgin JB, Barisoni L. Ultrastructural Characterization of Proteinuric Patients Predicts Clinical Outcomes. J Am Soc Nephrol. 2020 Apr;31(4):841–854.

Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

April 2020

Volume

31

Issue

4

Start / End Page

841 / 854

Location

United States

Related Subject Headings

  • Young Adult
  • Urology & Nephrology
  • Reproducibility of Results
  • Proteinuria
  • Prognosis
  • Predictive Value of Tests
  • Podocytes
  • Nephrosis, Lipoid
  • Microscopy, Electron
  • Male