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Abstract: PO2004

Sources of Variability in Podocyte Foot Process Width Measurements and Approaches to Mitigation

Session Information

  • Podocyte Biology
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

  • 1204 Podocyte Biology

Authors

  • Geraghty, Molly, Boston Medical Center, Boston, Massachusetts, United States
  • Thompson, Morgan P., Boston Medical Center, Boston, Massachusetts, United States
  • Gorman, Donal, Pfizer Inc, New York, New York, United States
  • Chen, Hui, Boston Medical Center, Boston, Massachusetts, United States
  • Atkuri, Kondala R., Pfizer Inc, New York, New York, United States
  • Berasi, Stephen, Pfizer Inc, New York, New York, United States
  • Copley, J. Brian, Pfizer Inc, New York, New York, United States
  • Henderson, Joel M., Boston Medical Center, Boston, Massachusetts, United States
Background

Podocyte foot process (FP) morphometry is used in the research setting to quantify podocyte injury and has the potential to be leveraged for diagnostic use. However, the impact of pre-analytic and analytic variables on these measurements are not well understood. We sought to identify these sources of variability and develop a robust method for podocyte foot process width (FPW) measurement within various kidney diseases.

Methods

We examined the impact of operator bias and sample size on FPW measurement in electron micrographs from nephrectomies (Nx) and podocytopathy (Px) cases, including primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD), and other glomerular lesions effecting the podocyte. FPW was measured for each individual FP between the midpoints of flanking filtration slits and the geometric mean of these measurements was reported by image. We found that identification of filtration slits was subjective, but interoperator variability was mitigated through use of standardized morphologic criteria, operator training, adjudication of ambiguous features, and a mapping process that eliminated duplicate measurements in adjacent images. These methods reduced interoperator variability in FPW, averaged by image, from 12% to 7%.

Results

Preliminary analysis suggests that, in addition to the expected larger FPW mean in MCD cases vs. Nx cases, there is also larger FPW variability in MCD cases. Related analysis shows ~125 FPW measurements within each of 2 glomeruli (~250 total) in a Nx case has the same precision as ~100 FPW measurements in each of 10 glomeruli (~1,000 total) in a MCD case. We also found that intraglomerular variability among 3 glomeruli in each of 2 cases (1 Nx, 1 MCD) ranged from 29% to 46% (Geometric CV), whereas interglomerular variability within these cases ranged from 0.5% to 6.3%, signifying that number and selection of FP within glomeruli is more impactful than number and selection of glomeruli within a specimen.

Conclusion

Our results suggest that careful measurement standardization and sampling improves validity of FPW measurements as a supplement to other diagnostic approaches or for assessment of podocyte injury in the course of treatment.

Funding

  • Commercial Support