New insights on glomerular hyperfiltration: a Japanese autopsy study

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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 (NglomTOTAL) as well as numbers of nonsclerosed (NglomNSG) and globally sclerosed glomeruli (NglomGSG), and the mean volume of nonsclerosed glomeruli (VglomNSG) 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 VglomNSG estimated using disector/fractionator stereology. Subject eGFR, single-nephron eGFR (SNeGFR), and the ratio SNeGFR/VglomNSG were calculated. NglomNSG 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 NglomNSG (r = 0.70, P < 0.001) and inversely correlated with VglomNSG (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/VglomNSG 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/VglomNSG 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.

Authors

Go Kanzaki, Victor G. Puelles, Luise A. Cullen-McEwen, Wendy E. Hoy, Yusuke Okabayashi, Nobuo Tsuboi, Akira Shimizu, Kate M. Denton, Michael D. Hughson, Takashi Yokoo, John F. Bertram