Kidney Week

Abstract: FR-PO144

Single Nephron Dynamics in Patients with Obesity-Related Glomerulopathy

Session Information

• Molecular Mechanisms of CKD - II
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1903 CKD (Non-Dialysis): Mechanisms

Authors

• Okabayashi, Yusuke, The Jikei University School of Medicine, Tokyo, Japan

Yusuke Okabayashi,

• Tsuboi, Nobuo, The Jikei University School of Medicine, Tokyo, Japan

Nobuo Tsuboi,

• Sasaki, Takaya, The Jikei University School of Medicine, Tokyo, Japan

Takaya Sasaki,

• Haruhara, Kotaro, The Jikei University School of Medicine, Tokyo, Japan

Kotaro Haruhara,

• Kanzaki, Go, The Jikei University School of Medicine, Tokyo, Japan

Go Kanzaki,

• Koike, Kentaro, The Jikei University School of Medicine, Tokyo, Japan

Kentaro Koike,

• Shimizu, Akira, Nippion Medical School, Tokyo, Japan

Akira Shimizu,

• Yokoo, Takashi, The Jikei University School of Medicine, Tokyo, Japan

Takashi Yokoo,

Background

The etiologies and mechanisms underlying the progression of obesity-related glomerulopathy (ORG) remain largely unknown, and the urinary protein excretion (UPE) level is the only predictive factor for renal outcome. ORG is characterized by renal histopathological findings of low glomerular density with glomerulomegaly, related to glomerular hyperfiltration. In this study, we estimated total nephron number and related factors in patients with ORG at different stages of the disease.

Methods

The total nephron number was calculated using a simplified method based on combined use of unenhanced computed tomography and non-sclerotic glomerular density in renal biopsy. Single-nephron glomerular filtration rate (snGFR) and single-nephron UPE (snUPE) were calculated by dividing eGFR or UPE by total nephron number, respectively. The glomerular volume (GV) was estimated from the measured mean glomerular area. Obese kidney transplantation donors were included in the study as a control group.

Results

Among the 30 Japanese ORG patients included in the study, total nephron number ranged from 153000 to 1061000 per kidney and was inversely correlated with GV (r = –0.366, p = 0.047). The snGFR was correlated with GV (r = 0.631, p < 0.001), and snUPE was correlated with the degree of glomerulosclerosis (r = 0.633, p < 0.001). None of these parameters associated with total nephron number showed a correlation with body mass index (BMI). Patients with advanced renal impairment were characterized by diminished snGFR and markedly elevated snUPE level (Figure). Among the ORG patients with preserved renal function (eGFR ≧ 45 mL/min/1.73 m², n = 22), total nephron number was identified as a factor associated with UPE at diagnosis, independent of eGFR and BMI.

Conclusion

There is a close relationship between difference in total nephron number and severity of ORG, in relation to changes in the single nephron dynamics. Compensatory failure of glomerular hyperfiltration may be a characteristic of advanced ORG.