Kidney Week

Abstract: SA-PO300

Morphometric Analysis of Different Nephron Segments in Patients with Diabetic Nephropathy and Overt Proteinuria

Session Information

• Diabetic Kidney Disease: Clinical Pathology, Diagnostic and Treatment Advances
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Miura, Akane, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan

Akane Miura, MD

• Okabe, Masahiro, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan

Masahiro Okabe, MD, PhD

• Sasaki, Takaya, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan

Takaya Sasaki, MD

• Okabayashi, Yusuke, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan

Yusuke Okabayashi, MD, PhD

• Haruhara, Kotaro, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan

Kotaro Haruhara, MD, PhD

• Tsuboi, Nobuo, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan

Nobuo Tsuboi, MD, PhD, FASN

• Yokoo, Takashi, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan

Takashi Yokoo, MD, PhD

Group or Team Name

• Dept of Nephrology and Hypertension, The Jikei University School of Medicine.

Background

Patients with diabetic nephropathy (DN) are characterized by kidney enlargement, and heavy proteinuria is associated with poor kidney function outcomes. The relationship between hypertrophic changes in single nephrons and the development of proteinuria has not been studied in DN patients.

Methods

Glomerular volume (V_glom), proximal tubular diameter (D_prox) and distal tubular diameter (D_dist) were measured using biopsy specimens from DN patients with overt proteinuria. Nephron-related parameters were estimated using combination of computed tomography imaging and biopsy stereology. These include number of total non-globally sclerotic glomeruli (N_NSG), number of globally sclerotic glomeruli (N_GSG) and single-nephron GFR (SNGFR), which was estimated by deviding eGFR by N_NSG of both kidneys. The proteinuria level at biopsy were compared among tertile groups based on V_glom, D_prox, and D_dist.

Results

A total 78 patients were included in this study (median 56 [quartile 46-67] years, 82% male, eGFR 40.0 [27.4-53.5] ml/min/1.73m², urinary protein 4.3 [2.0-6.9] g/day). Of the V_glom, D_prox, and D_dist tertiles, only D_prox showed a significant trend to correlate with urinary protein levels (Figure). Among the D_prox tertile, there were no differences in age, sex, hypertension, eGFR, and HbA1c among the groups, while body mass index showed an increasing trend with D_prox. N_NSG, N_GSG, and SNGFR were not statistically different among the D_prox tertile. D_prox showed an increasing trend with glomerular lesions characteristic of DN, but V_glom, and D_dist did not show such a trend.

Conclusion

The present study is the first to morphologically demonstrate the involvement of proximal tubular hypertrophy in the pathophysiology of proteinuria in DN. Morphological findings of different nephron segments, as shown in this study, may provide clinically useful insights when combined with response to treatment and kidney function outcomes.

Comparison of proteinuria levels according to morphological measurement of different nephron segments