Kidney Week

Abstract: SA-PO917

Stenosis of the Glomerulotubular Neck Is Associated with Progressive CKD

Session Information

• Pathology and Lab Medicine - 2
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

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

Eric P. Cohen, MD

• Denic, Aleksandar, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Aleksandar Denic, MD, PhD

• Gibson, Ian W., University of Manitoba Max Rady College of Medicine, Winnipeg, Manitoba, Canada

Ian W. Gibson, MD, MBChB

• Aperna, Fnu, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Fnu Aperna, MBBS

• Rule, Andrew D., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Andrew D. Rule, MD, MS, FASN

Background

Histopathologic evaluation can clarify the pathophysiology of chronic kidney disease (CKD). We tested whether the occurrence of glomerulotubular neck stenoses associates with progressive CKD.

Methods

We evaluated the non-cancerous parenchyma from radical nephrectomies for tumor between 2000 and 2021 and analyzed the cortex for stenoses of the glomerulotubular neck. Stenosis was defined as a focal narrowing at the neck for which the draining tubule had a greater diameter than at the neck (Figure 1B). Progressive CKD was defined as dialysis, kidney transplantation, sustained eGFR <10 ml/min per 1.73m² or sustained 40% decline from the post-nephrectomy eGFR during follow-up. Each case of progressive CKD was age-sex-matched to 2 controls without progressive CKD. Logistic regression models assessed the risk of progressive CKD with stenotic necks adjusting for other histological features, kidney function, and CKD risk factors.

Results

There were 65 cases with a mean of 255 glomeruli and 130 controls with a mean of 329 glomeruli. Among both cases and controls, 5% of glomeruli showed visible glomerulotubular necks. The proportion of necks that were stenotic was higher in cases than controls (35% vs. 11%, p<0.0001). Stenotic necks associated with progressive CKD independent of other histologic and clinical characteristics. ROC curves for histological morphometric measures showed that the proportion of stenotic necks was superior to glomerular volume, %GSG, and % IFTA as a classifier for predicting progressive CKD (Figure 1C).

Conclusion

Glomerulotubular neck stenosis predicts progressive CKD.

Representative images of glomerulotubular necks that are A) normal (non-stenotic), and B) stenotic. C) ROC curves for histological pathology by morphometry as a classifier for subsequent progressive CKD among patients who underwent radical nephrectomy for tumor. The area under the curve (AUC) was 0.847 (95%CI: 0.776 to 0.917) for % stenotic glomerulotubular necks, 0.715 (95%CI: 0.638 to 0.793) for glomerular volume, 0.707 (95%CI: 0.623 to 0.790) for % globally sclerotic glomeruli (%GSG), and 0.695 (95%CI: 0.617 to 0.772) for % interstitial fibrosis and tubular atrophy (%IFTA).

Funding

• NIDDK Support