G KANZAKI1,2, VG PUELLES3, LA CULLEN-MCEWEN1, Y OKABAYASHI2, N TSUBOI2, A SHIMIZU4, T YOKOO2, JF BERTRAM1
1Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Melbourne, Victoria; 2Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan; 3Department of Nephrology and Immunology, RWTH Aachen University, Aachen, Germany; 4Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan
Aim: The aim of this study was to evaluate the relationship between nephron number and the stage of chronic kidney disease (CKD) in Japanese adults.
Background: It has been proposed that a nephron deficit marks 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 59 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=25, eGFR 89-60 mL/min), and CKD stage 3-4 (n=21, eGFR 60-15 mL/min). Total nephron number and mean glomerular volume 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 was significantly lower in CKD stage 3-4 (293,558±89,716; mean±SD; P<0.001) than in CKD stage 1 (631,980±159,755) and CKD stage 2 (504,716±130,342. Kidney weights and cortical volumes were similar in the three groups. Glomeruli were larger in CKD stage 3-4 (P<0.001) than in CKD stages 1 and 2. No differences in total glomerular volume (combined volume of all non-sclerotic glomeruli) or SNeGFR were observed between the three groups.
Conclusions: 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.