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Abstract: TH-PO534

The Location and Character of Focal Segmental Glomerulosclerosis Lesions: The Prevalence, Overlap, and Clinical Relevance

Session Information

  • Pathology and Lab Medicine
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

  • 1700 Pathology and Lab Medicine

Authors

  • Ozeki, Takaya, University of Michigan, Ann Arbor, Michigan, United States
  • Yamashita, Michifumi, Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Alakwaa, Fadhl, University of Michigan, Ann Arbor, Michigan, United States
  • Nair, Viji, University of Michigan, Ann Arbor, Michigan, United States
  • Zee, Jarcy, University of Pennsylvania, and Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Hodgin, Jeffrey B., University of Michigan, Ann Arbor, Michigan, United States
  • Bu, Lihong, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Rosenberg, Avi Z., Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Nast, Cynthia C., Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
  • Barisoni, Laura, Duke University, Durham, North Carolina, United States
  • Mariani, Laura H., University of Michigan, Ann Arbor, Michigan, United States
Background

The glomerular lesions in focal segmental glomerulosclerosis (FSGS) are histologically heterogeneous for location (L) and characteristics (C). The aim of this study is to investigate the quantitative relationship and clinical relevance of L and C of FSGS lesions.

Methods

134 FSGS participants from the Nephrotic Syndrome Study Network (NEPTUNE) with NEPTUNE digital pathology scoring system (NDPSS) glomerular descriptors, were included. 21 descriptors characterizing L and C of FSGS lesions were grouped into 4 L: Perihilar (PH), Tip (TIP), Mid-glomerular, and Undetermined (UN); and 7 C: Sclerosis (SCL), Hyalinosis (HYA), Cellular-lesion (CEL), Foam cells, Collapsing-lesion (COL), Epithelial hypertrophy, and Epithelial hyperplasia (HYP). Prevalence and correlations of L and C were analyzed. Patients were grouped based on L or C using consensus clustering. Complete remission (CR) and composite renal outcome (eGFR 40% decline or ESKD) were compared among L-based and C-based clusters by Kaplan-Meier method. Subgroup analyses were performed in nephrotic (NS) (UPCR>3.5 with albumin<3.0 or diffuse foot process effacement, n=41) and non-NS group (n=93).

Results

863/4614 (18.7%) glomeruli contained at least 1 of 21 descriptors. >2 L or C were observed in 48.3% and 91.0% of the biopsies, respectively. Correlations with Spearman’s rho>0.5 were observed in TIP-CEL, UN-SCL and COL-HYP. TIP and CEL were more frequent in NS group, while PH, SCL and HYA were more frequent in non-NS group. There were no differences in the clinical outcomes among the L-based nor C-based clusters in overall cohort and non-NS group. In NS group, a difference in CR was observed between 2 C-based (but not L-based) clusters in NS group (p=0.048): A cluster with worse CR rate had higher frequency of all 7 C lesions than the better CR cluster.

Conclusion

The application of NDPSS allowed for the quantification of heterogeneity and overlap in location and morphologic characters of FSGS lesions within and across kidney biopsies, with different trends between NS and non-NS participants. In NS participants, high frequency and more variety of C were associated with lower CR rate; while neither L nor C showed impact on clinical outcomes in non-NS participants and NS + non-NS participants together.

Funding

  • NIDDK Support