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Kidney Week

Abstract: TH-PO0402

Parietal Epithelial Cell (PEC) Hypertrophy and Hyperplasia Are Correlates of Kidney Injury and Treatment Response in Children with Lupus Nephritis

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

  • Hodgin, Jeffrey B., University of Michigan, Ann Arbor, Michigan, United States
  • Ahmadian, Mansooreh, University of Colorado System, Denver, Colorado, United States
  • Rickert, Christian, University of Colorado System, Denver, Colorado, United States
  • Jordan, Kimberly R., University of Colorado System, Denver, Colorado, United States
  • Hsieh, Eena, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background

Childhood SLE (cSLE) carries a disproportionate burden of lupus nephritis (cLN), affecting >60% of patients. Failure to achieve renal remission at 6–12 months predicts progression to end-stage renal disease. Glomerular cellular mechanisms driving cLN remain poorly understood. We performed glomerular descriptor scoring and multiplexed single-cell immune profiling on FFPE renal biopsies to identify histologic and cellular correlates of renal function and treatment response.

Methods

We studied biopsies from 28 cLN cases and 5 healthy controls. Two pathologists performed structured glomerular descriptor scoring. Multiplexed ion beam imaging (MIBI) with a 36-plex panel resolved major immune subsets including T and B cells, plasma, NK, neutrophils, macrophages, and dendritic cells. 413,155 cells and 316 glomeruli were analyzed. Descriptor features were correlated with eGFR and UPCR at biopsy and with glomerular immune composition. Treatment response was assessed by eGFR and UPCR change at 12 months.

Results

PEC hypertrophy and hyperplasia correlated negatively with eGFR and positively with UPCR (all p<0.05). Mesangial neutrophils correlated negatively with eGFR; crescents, necrosis, and adhesions correlated positively with UPCR. PEC hyperplasia correlated with CD4+CD14+ cells; mesangial neutrophils with CD4+ T cells; and fibrocellular crescents with CD4+CD16+ cells. PEC hyperplasia and karyorrhexis independently predicted poorer treatment response in multivariable analysis.

Conclusion

PEC activation may be a central correlate of renal functional impairment and treatment resistance in cLN. Associations between descriptor features and immune subsets support a spatially organized glomerular immune response. These findings highlight PEC-targeted analysis as a promising avenue for biomarker development and therapeutic targeting in cLN.

Funding

  • NIDDK Support