Associations between nephron number and podometrics in human kidneys
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Associations between nephron number and podometrics in human kidneys. / Haruhara, Kotaro; Kanzaki, Go; Sasaki, Takaya; Hatanaka, Saeko; Okabayashi, Yusuke; Puelles, Victor G; Harper, Ian S; Shimizu, Akira; Cullen-McEwen, Luise A; Tsuboi, Nobuo; Yokoo, Takashi; Bertram, John F.
In: KIDNEY INT, Vol. 102, No. 5, 11.2022, p. 1127-1135.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Associations between nephron number and podometrics in human kidneys
AU - Haruhara, Kotaro
AU - Kanzaki, Go
AU - Sasaki, Takaya
AU - Hatanaka, Saeko
AU - Okabayashi, Yusuke
AU - Puelles, Victor G
AU - Harper, Ian S
AU - Shimizu, Akira
AU - Cullen-McEwen, Luise A
AU - Tsuboi, Nobuo
AU - Yokoo, Takashi
AU - Bertram, John F
N1 - Copyright © 2022 International Society of Nephrology. All rights reserved.
PY - 2022/11
Y1 - 2022/11
N2 - Podocyte loss and resultant nephron loss are common processes in the development of glomerulosclerosis and chronic kidney disease. While the cortical distribution of glomerulosclerosis is known to be non-uniform, the relationship between the numbers of non-sclerotic glomeruli (NSG), podometrics and zonal differences in podometrics remain incompletely understood. To help define this, we studied autopsy kidneys from 50 adults with median age 68 years and median eGFR 73.5 mL/min/1.73m2 without apparent glomerular disease in a cross-sectional analysis. The number of NSG per kidney was estimated using the physical dissector/fractionator combination, while podometrics were estimated using model-based stereology. The number of NSG per kidney was directly correlated with podocyte number per tuft and podocyte density. Each additional 100,000 NSG per kidney was associated with 26 more podocytes per glomerulus and 16 podocytes per 106 μm3 increase in podocyte density. These associations were independent of clinical factors and cortical zone. While podocyte number per glomerulus was similar in the three zones, superficial glomeruli were the smallest and had the highest podocyte density but smallest podocytes. Increasing age and hypertension were associated with lower podocyte number, with age mostly affecting superficial glomeruli, and hypertension mostly affecting juxtamedullary glomeruli. Thus, in this first study to report a direct correlation between the number of NSG and podometrics, we suggest that podocyte number is decreasing in NSG of individuals losing nephrons. However, another possible interpretation may be that more nephrons might protect against further podocyte loss.
AB - Podocyte loss and resultant nephron loss are common processes in the development of glomerulosclerosis and chronic kidney disease. While the cortical distribution of glomerulosclerosis is known to be non-uniform, the relationship between the numbers of non-sclerotic glomeruli (NSG), podometrics and zonal differences in podometrics remain incompletely understood. To help define this, we studied autopsy kidneys from 50 adults with median age 68 years and median eGFR 73.5 mL/min/1.73m2 without apparent glomerular disease in a cross-sectional analysis. The number of NSG per kidney was estimated using the physical dissector/fractionator combination, while podometrics were estimated using model-based stereology. The number of NSG per kidney was directly correlated with podocyte number per tuft and podocyte density. Each additional 100,000 NSG per kidney was associated with 26 more podocytes per glomerulus and 16 podocytes per 106 μm3 increase in podocyte density. These associations were independent of clinical factors and cortical zone. While podocyte number per glomerulus was similar in the three zones, superficial glomeruli were the smallest and had the highest podocyte density but smallest podocytes. Increasing age and hypertension were associated with lower podocyte number, with age mostly affecting superficial glomeruli, and hypertension mostly affecting juxtamedullary glomeruli. Thus, in this first study to report a direct correlation between the number of NSG and podometrics, we suggest that podocyte number is decreasing in NSG of individuals losing nephrons. However, another possible interpretation may be that more nephrons might protect against further podocyte loss.
KW - Adult
KW - Humans
KW - Aged
KW - Cross-Sectional Studies
KW - Kidney Glomerulus
KW - Podocytes
KW - Kidney
KW - Hypertension
U2 - 10.1016/j.kint.2022.07.028
DO - 10.1016/j.kint.2022.07.028
M3 - SCORING: Journal article
C2 - 36175177
VL - 102
SP - 1127
EP - 1135
JO - KIDNEY INT
JF - KIDNEY INT
SN - 0085-2538
IS - 5
ER -
