Abstract: FR-PO409

Total Nephron Number Decreases with the Stage of CKD – A Study in Japanese Subjects

Session Information

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)
Nglom591,377±238,149505,303±132,917293,198±110,087<0.001
Vglom (x106 µm3)6.39±1.797.09±1.5310.52±3.77<0.001
total glomerular volume (cm3)3.42±1.123.21±0.892.48±1.170.038
Cortical volume (cm3)84.8±29.880.8±19.565.3±20.60.038
SNeGFR (nl/min/1.73m2)119.3±54.186.8±24.897.3±44.80.2771
SNeGFR/Vglom (ml/min/1.73m2/cm3)19.0±8.112.6±3.710.3±6.3<0.001

mean±SD