Abstract: FR-PO409
Total Nephron Number Decreases with the Stage of CKD – A Study in Japanese Subjects
Session Information
- CKD: Risk Factors for Incidence and Progression - I
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Chronic Kidney Disease (Non-Dialysis)
- 301 CKD: Risk Factors for Incidence and Progression
Authors
- Kanzaki, Go, The Jikei University School of Medicine, Tokyo, TOKYO, Japan
- Puelles, Victor G., University Hospital RWTH Aachen, Aachen, Germany
- Cullen-McEwen, Luise A., Monash University, Melbourne, Victoria, Australia
- Okabayashi, Yusuke, The Jikei University School of Medicine, Tokyo, TOKYO, Japan
- Tsuboi, Nobuo, The Jikei University School of Medicine, Tokyo, TOKYO, Japan
- Shimizu, Akira, Nippion Medical School, Tokyo, Japan
- Yokoo, Takashi, The Jikei University School of Medicine, Tokyo, TOKYO, Japan
- Bertram, John F., Monash University, Melbourne, Victoria, Australia
Background
There is increasing evidence that low nephron number increases the risk for CKD. We have previously shown that nephron number predicts eGFR. However, changes in total nephron number across the stages of CKD have not previously been reported. In this study we assessed total nephron number and clinicopathological findings in Japanese subjects in order to determine the structural and functional changes associated with nephron loss in each CKD stage.
Methods
Kidneys from 58 Japanese subjects were collected at Nippon Medical School, Tokyo, Japan during autopsy and were divided into three groups; CKD stage 1 (n=13, eGFR>90 mL/min), CKD stage 2 (n=24, eGFR 89-60 mL/min), and CKD stage 3-4 (n=21, eGFR 59-15 mL/min). Total nephron number (Nglom) and mean glomerular volume (Vglom) were estimated by design-based stereology. Single nephron eGFR (SNeGFR) was calculated as eGFR divided by two times the number of non-sclerotic glomeruli.
Results
Total nephron number per kidney was significantly lower in CKD stage 3-4 (293,198±110,087; mean±SD; P<0.001) than in CKD stage 1 (591,377±238,149) and CKD stage 2 (505,303±132,917). Glomeruli were larger in CKD stage 3-4 (P<0.001) than in CKD stages 1 and 2. Kidney weights were similar in the three groups, even though subjects with CKD stage 3-4 had lower cortical volumes and total glomerular volume (combined volume of all non-sclerotic glomeruli) than with CKD stages 1 and 2. Although no differences in SNeGFR were observed between the three groups, SNeGFR/Vglom, which predicts glomerular capillary filtration, was reduced in CKD stages 2 and 3-4 (P<0.001).
Conclusion
Compared with subjects with eGFR>60 mL/min, CKD stage 3-4 patients had an apparent nephron deficit, with glomerular hypertrophy partially compensating for the nephron loss. Our findings also suggest that glomerular capillary filtration starts decreasing in CKD stage 2.
Demographic and renal functional and structural data with CKD stages
| CKD stage1 (N=13) | CKD stage2 (N=24) | CKD stage3-4 (N=21) | ANOVA (P value) | |
| Nglom | 591,377±238,149 | 505,303±132,917 | 293,198±110,087 | <0.001 |
| Vglom (x106 µm3) | 6.39±1.79 | 7.09±1.53 | 10.52±3.77 | <0.001 |
| total glomerular volume (cm3) | 3.42±1.12 | 3.21±0.89 | 2.48±1.17 | 0.038 |
| Cortical volume (cm3) | 84.8±29.8 | 80.8±19.5 | 65.3±20.6 | 0.038 |
| SNeGFR (nl/min/1.73m2) | 119.3±54.1 | 86.8±24.8 | 97.3±44.8 | 0.2771 |
| SNeGFR/Vglom (ml/min/1.73m2/cm3) | 19.0±8.1 | 12.6±3.7 | 10.3±6.3 | <0.001 |
mean±SD