Takaya Sasaki1, Nobuo Tsuboi2, Go Kanzaki1, Kotaro Haruhara1, Yusuke Okabayashi1, Kentaro Koike1, Akimitsu Kobayashi1, Izumi Yamamoto1, Makoto Ogura1, Wendy E Hoy3, John F Bertram4, Akira Shimizu5, Takashi Yokoo1. 1. Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo, Japan. 2. Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo, Japan. tsuboi-n@jikei.ac.jp. 3. Centre for Chronic Disease, The University of Queensland, Brisbane, Australia. 4. Department of Anatomy and Developmental Biology and Biomedical Discovery Institute, Monash University, Melbourne, Australia. 5. Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
Abstract
BACKGROUND: Increasing evidence suggests that individuals with low nephron number have an increased lifetime risk of renal insufficiency, thereby emphasizing the importance of evaluating total nephron number in each individual. In recent years, new methods have been described for estimating human total nephron number using a combination of image analysis and renal biopsy, though the reproducibility and accuracy of these methods remain uncertain. This study estimated total nephron number in healthy Japanese subjects using such a method. METHODS: Implantation biopsies from 44 living kidney donors were analyzed. Using pre-donation contrast CT angiograms, transplantation donor kidneys were three-dimensionally reconstructed, and total renal cortical volume was estimated. Total nephron number was estimated based on glomerular density in biopsy specimens and total renal cortical volume. The obtained results were analyzed in relation to clinical variables and compared with those of a previously reported Japanese autopsy study. RESULTS: The estimated non-sclerotic and total numbers of glomeruli in this cohort were 650,000 ± 220,000 and 710,000 ± 220,000 (mean ± SD) per kidney. Non-sclerotic glomerular number ranged from 280,000 to 1,220,000 per kidney (4.4-fold) and correlated directly with eGFR (r = 0.328, p = 0.030) and inversely with age (r = - 0.355, p = 0.018). CONCLUSION: The estimated total nephron number obtained in the present study was 25% less than that reported in American living kidney donors obtained using the same procedure and similar to that obtained in a previous Japanese autopsy study using the disector/fractionator method. These results confirm the feasibility of a combined CT angiography and biopsy-based method to estimate total nephron number in humans.
BACKGROUND: Increasing evidence suggests that individuals with low nephron number have an increased lifetime risk of renal insufficiency, thereby emphasizing the importance of evaluating total nephron number in each individual. In recent years, new methods have been described for estimating humantotal nephron number using a combination of image analysis and renal biopsy, though the reproducibility and accuracy of these methods remain uncertain. This study estimated total nephron number in healthy Japanese subjects using such a method. METHODS: Implantation biopsies from 44 living kidney donors were analyzed. Using pre-donation contrast CT angiograms, transplantation donor kidneys were three-dimensionally reconstructed, and total renal cortical volume was estimated. Total nephron number was estimated based on glomerular density in biopsy specimens and total renal cortical volume. The obtained results were analyzed in relation to clinical variables and compared with those of a previously reported Japanese autopsy study. RESULTS: The estimated non-sclerotic and total numbers of glomeruli in this cohort were 650,000 ± 220,000 and 710,000 ± 220,000 (mean ± SD) per kidney. Non-sclerotic glomerular number ranged from 280,000 to 1,220,000 per kidney (4.4-fold) and correlated directly with eGFR (r = 0.328, p = 0.030) and inversely with age (r = - 0.355, p = 0.018). CONCLUSION: The estimated total nephron number obtained in the present study was 25% less than that reported in American living kidney donors obtained using the same procedure and similar to that obtained in a previous Japanese autopsy study using the disector/fractionator method. These results confirm the feasibility of a combined CT angiography and biopsy-based method to estimate total nephron number in humans.
Authors: Elise Marechal; Adrien Jaugey; Georges Tarris; Michel Paindavoine; Jean Seibel; Laurent Martin; Mathilde Funes de la Vega; Thomas Crepin; Didier Ducloux; Gilbert Zanetta; Sophie Felix; Pierre Henri Bonnot; Florian Bardet; Luc Cormier; Jean-Michel Rebibou; Mathieu Legendre Journal: Clin J Am Soc Nephrol Date: 2021-12-03 Impact factor: 8.237
Authors: Darya Morozov; Neda Parvin; Mark Conaway; Gavin Oxley; Edwin J Baldelomar; Aleksandra Cwiek; Kim deRonde; Scott C Beeman; Jennifer R Charlton; Kevin M Bennett Journal: J Am Soc Nephrol Date: 2021-11-10 Impact factor: 10.121
Authors: C L Walsh; P Tafforeau; W L Wagner; D J Jafree; A Bellier; C Werlein; M P Kühnel; E Boller; S Walker-Samuel; J L Robertus; D A Long; J Jacob; S Marussi; E Brown; N Holroyd; D D Jonigk; M Ackermann; P D Lee Journal: Nat Methods Date: 2021-11-04 Impact factor: 28.547
Authors: Kotaro Haruhara; Takaya Sasaki; Natasha de Zoysa; Yusuke Okabayashi; Go Kanzaki; Izumi Yamamoto; Ian S Harper; Victor G Puelles; Akira Shimizu; Luise A Cullen-McEwen; Nobuo Tsuboi; Takashi Yokoo; John F Bertram Journal: J Am Soc Nephrol Date: 2021-02-24 Impact factor: 10.121