New insights on glomerular hyperfiltration: a Japanese autopsy study

Kanzaki, Go, Puelles, Victor G., Cullen-McEwen, Luise A., Hoy, Wendy E., Okabayashi, Yusuke, Tsuboi, Nobuo, Shimizu, Akira, Denton, Kate M., Hughson, Michael D., Yokoo, Takashi and Bertram, John F. (2017) New insights on glomerular hyperfiltration: a Japanese autopsy study. Jci Insight, 2 19: 1-11. doi:10.1172/jci.insight.94334

Author Kanzaki, Go
Puelles, Victor G.
Cullen-McEwen, Luise A.
Hoy, Wendy E.
Okabayashi, Yusuke
Tsuboi, Nobuo
Shimizu, Akira
Denton, Kate M.
Hughson, Michael D.
Yokoo, Takashi
Bertram, John F.
Title New insights on glomerular hyperfiltration: a Japanese autopsy study
Journal name Jci Insight   Check publisher's open access policy
ISSN 2379-3708
Publication date 2017-10-05
Year available 2017
Sub-type Article (original research)
DOI 10.1172/jci.insight.94334
Open Access Status DOI
Volume 2
Issue 19
Start page 1
End page 11
Total pages 11
Place of publication ANN ARBOR
Language eng
Abstract It has been suggested that low nephron number contributes to glomerular hypertension and hyperperfusion injury in progressive chronic kidney disease (CKD). The incidence of CKD in Japan is among the highest in the world, but the reasons remain unclear. We estimated total nephron (glomerular) number (Nglom TOTAL) as well as numbers of nonsclerosed (Nglom NSG) and globally sclerosed glomeruli (Nglom GSG), and the mean volume of nonsclerosed glomeruli (Vglom NSG) in Japanese normotensive, hypertensive, and CKD subjects and investigated associations between these parameters and estimated glomerular filtration rate (eGFR). Autopsy kidneys from age-matched Japanese men (9 normotensives, 9 hypertensives, 9 CKD) had nephron number and Vglom NSG estimated using disector/fractionator stereology. Subject eGFR, single-nephron eGFR (SNeGFR), and the ratio SNeGFR/Vglom NSG were calculated. Nglom NSG in Japanese with hypertension (392,108 +/- 87,605; P < 0.001) and CKD (268,043 +/- 106,968; P < 0.001) was less than in normotensives (640,399 +/- 160,016). eGFR was directly correlated with Nglom NSG (r = 0.70, P < 0.001) and inversely correlated with Vglom NSG (r = -0.53, P < 0.01). SNeGFR was higher in hypertensives than normotensives (P = 0.03), but was similar in normotensives and CKD, while the ratio SNeGFR/Vglom NSG was similar in normotensives and hypertensives but markedly reduced in CKD. Nephron number in Japanese with hypertension or CKD was low. This results in a higher SNeGFR in hypertensives compared with normotensive and CKD subjects, but lowered SNeGFR/Vglom NSG in CKD subjects, suggesting that changes in GFR are accommodated by glomerular hypertrophy rather than glomerular hypertension. These findings suggest glomerular hypertrophy is a dominant factor in maintenance of GFR under conditions of low nephron number.
Keyword Chronic Kidney-Disease
Nephron Number
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID JP25461236
NHMRC 1128582
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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Created: Sun, 05 Nov 2017, 09:27:21 EST