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Abstract: SA-PO916

Stenosis of Glomerulotubular Necks in a CKD Model

Session Information

Category: Pathology and Lab Medicine

  • 1800 Pathology and Lab Medicine

Authors

  • Cohen, Eric P., New York University Grossman School of Medicine, New York, New York, United States
  • Farese, Ann M., University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Parker, George A., Charles River Laboratories International Inc, Durham, North Carolina, United States
  • Macvittie, Thomas J., University of Maryland School of Medicine, Baltimore, Maryland, United States
Background

Fibrosis is a marker of injury and a predictor of future loss of renal function. Its intra-renal location may have more significance than its generalized presence. Histological studies of single time points show that fibrotic constriction of the glomerulotubular neck (GTN) may play a mechanistic role to impair nephron function (Cohen, J Lab Clin Med 129:567, Sato, J Pathol 197:14). We thus evaluated the time-course of the presence of GTN in a non-human primate (NHP) model of chronic kidney disease (CKD) and show that stenotic GTN increase over time in parallel with loss of renal function.

Methods

38 NHP underwent 10 or 11 Gy partial-body irradiation (PBI) with tibial bone marrow sparing. Eleven NHP were non-irradiated (0 Gy). This model reliably causes progressive fibrotic CKD within months after irradiation (Cohen, Radiat Res 188:741). Kidneys were obtained at planned or for-cause euthanasia, whole kidney sections stained with Trichrome, then analyzed in a masked fashion using whole slide scanning. 40 or more glomeruli were identified in each section. Where seen, stenotic GTNs were defined as a narrowing at the beginning of the proximal tubule, while patent GTNs showed no narrowing at that site.

Results

5%, 3%, and 4% of all glomeruli had visible necks in the 0, 10, and 11 Gy NHP, respectively. 15%, 21%, and 40% of visible necks were stenotic in the 0, 10, and 11 Gy NHP, respectively. The ratio of stenotic to normal necks was 0.2, 0.3, and 0.6 in the 0, 10, and 11 Gy NHP, respectively. The number of patent necks decreased over time after irradiation (figure). The % of visible necks that were stenotic increased progressively over time after irradiation. The serum creatinine increased in parallel to the increase in stenotic necks.

Conclusion

In conclusion, stenosis of the glomerulotubular neck is a definite feature of fibrotic chronic kidney disease. Further study is needed to identify the mechanisms whereby stenotic GTN form, and to identify markers of their presence in life.

Figure 1: The left hand panel shows a glomerulus with a normal patent neck, the middle panel shows a stenotic neck, and the right hand panel shows the % of stenotic necks per 40 glomeruli for non-irradiated (●), 10 Gy ( △ ), and 11 Gy irradiated NHP ( ▽ ).

Funding

  • Other NIH Support