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Abstract: FR-PO993

The Use of Quantitative Morphometrics in Nephrectomy Specimens to Understand Focal Segmental Glomerulosclerosis

Session Information

Category: Pathology and Lab Medicine

  • 1602 Pathology and Lab Medicine: Clinical

Authors

  • O'Connor, Christopher Lund, University of Michigan, Ann Arbor, Michigan, United States
  • Schaub, Jennifer A., University of Michigan, Ann Arbor, Michigan, United States
  • Hodgin, Jeffrey B., The University of Michigan, Ann Arbor, Michigan, United States
  • Wiggins, Roger C., University of Michigan Health System, Ann Arbor, Michigan, United States
  • Bitzer, Markus, University of Michigan, Ann Arbor, Michigan, United States
Background

Detection of a single segmentally sclerosed glomerulus is sufficient to establish the diagnosis of focal segmental glomerulosclerosis (FSGS), which guides management and prognosis of kidney function decline. Because 10-15 glomeruli are available for examination of standard kidney biopsies, glomerular lesions present in low frequency such as segmental glomerulosclerosis (SGS) may be missed. To determine the probability of detection of SGS and whether morphometric parameters in normal appearing glomeruli are associated with SGS, we evaluated larger kidney tissue samples from nephrectomy specimens.

Methods

We obtained specimens from 79 patients who underwent nephrectomy and abstracted clinical data from the patient’s electronic medical records. We analyzed PAS-stained kidney sections for global and segmental glomerulosclerosis, and quantified glomerular morphometrics using chemical and immunohistochemical stains. We estimated the probability that a biopsy would identify FSGS using the geometric distribution with varying frequencies of SGS lesions and number of glomeruli obtained in a kidney biopsy.

Results

The median number of glomeruli per specimen was 227. 44% of patients were classified as having FSGS as defined by the presence of at least one glomerulus with SGS. Of those, 18 (39.1%) had less than 1% of their glomeruli with an SGS lesion. Patients with FSGS were more likely to be diabetic (37.5% vs. 8.1%, p=0.003), hypertensive (48.3% vs. 29.7%, p=0.006) and have a lower baseline eGFR prior to nephrectomy (69.6 vs. 86.7 - ml/min/1.73m2, p=0.002). Patients with FSGS had increased glomerular volume (4.1 vs. 3.6 - 106µm3, p=0.04), decreased podocyte density (106.4 vs.129.3 - podocytes/106µm3, p=0.001), and increased podocyte volume (4885 vs 4100 - µm3, p=0.005). For low frequency SGS lesions (<1% of glomeruli), a kidney biopsy could miss a FSGS diagnosis more than 74% of the time.

Conclusion

Qualitative and quantitative morphometric analysis of nephrectomy specimens identify low frequency SGS lesions. Kidney biopsy can frequently miss an FSGS diagnosis if there is a low frequency of SGS lesions. Future directions involve examining the possibility of using computer aided quantitative morphometry in order to impute the existence of rare glomerular features unlikely to be captured during routine biopsy.

Funding

  • NIDDK Support