TY - JOUR
T1 - Glomerular volume and glomerulosclerosis at different depths within the human kidney
AU - Denic, Aleksandar
AU - Ricaurte, Luisa
AU - Lopez, Camden L.
AU - Narasimhan, Ramya
AU - Lerman, Lilach O.
AU - Lieske, John C.
AU - Houston Thompson, R.
AU - Kremers, Walter K.
AU - Rule, Andrew David
N1 - Funding Information:
Dr. Lieske reports grants and other from Alnylam, grants from Dicerna, grants from Retrophin, grants from Oxthera, grants from Siemens, other from Orfan, grants and other from Allena, outside the submitted work. Dr. Kremers reports grants from National Institutes of Health (NIH), during the conduct of the study; grants from AstraZeneca, grants from Roche, grants from Biogen, outside the submitted work. Dr. Rule reports grants from NIH/National Institute of Diabetes and Digestive and Kidney Diseases, during the conduct of the study. All of the remaining authors have nothing to disclose.
Funding Information:
This study was supported with funding from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK090358). Dr. Denic was supported by the Robert W. Fulk Career Development Award Fund in Nephrology Research Honoring Dr. Fernando Fervenza.
Publisher Copyright:
© 2019 by the American Society of Nephrology.
PY - 2019/8
Y1 - 2019/8
N2 - Background Age, CKD risk factors, and kidney function are associated with larger glomerular volume and a higher percentage of globally sclerotic glomeruli. Knowledge of how these associations may differ by cortical depth is limited. Methods To investigate glomerular volume and glomerulosclerosis across different depths of cortex, we studied wedge sections of the renal parenchyma from 812 patients who underwent a radical nephrectomy (for a tumor), separately characterizing glomeruli in the superficial (subcapsular), middle, and deep (juxta-medullary) regions. We compared the association of mean nonsclerotic glomerular volume and of glomerulosclerosis (measured as the percentage of globally sclerotic glomeruli) with age, obesity, diabetes, smoking, kidney function, and structural pathology in the superficial, middle, and deep regions. Results The superficial, middle, and deep regions showed significant differences in glomerular volume (0.0025, 0.0031, and 0.0028 µm3, respectively) and in glomerulosclerosis (18%, 7%, and 11%, respectively). There was a marked increase in glomerulosclerosis with age in the superficial region, but larger glomerular volume was not associated with age at any cortical depth. Glomerulosclerosis associated more strongly with arteriosclerosis and ischemic-appearing glomeruli in the superficial region. Hypertension, lower eGFR, and interstitial fibrosis associated with glomerulosclerosis and glomerular volume to a similar extent at any depth. Diabetes and proteinuria more strongly associated with glomerulosclerosis in the deep and middle regions, respectively, but neither associated with glomerular volume differently by depth. Obesity associated more strongly with glomerular volume in the superficial cortex. Conclusions Most clinical characteristic show similar associations with glomerulosclerosis and glomerulo-megaly at different cortical depths. Exceptions include age-related glomerulosclerosis, which appears to be an ischemic process and is more predominant in the superficial region.
AB - Background Age, CKD risk factors, and kidney function are associated with larger glomerular volume and a higher percentage of globally sclerotic glomeruli. Knowledge of how these associations may differ by cortical depth is limited. Methods To investigate glomerular volume and glomerulosclerosis across different depths of cortex, we studied wedge sections of the renal parenchyma from 812 patients who underwent a radical nephrectomy (for a tumor), separately characterizing glomeruli in the superficial (subcapsular), middle, and deep (juxta-medullary) regions. We compared the association of mean nonsclerotic glomerular volume and of glomerulosclerosis (measured as the percentage of globally sclerotic glomeruli) with age, obesity, diabetes, smoking, kidney function, and structural pathology in the superficial, middle, and deep regions. Results The superficial, middle, and deep regions showed significant differences in glomerular volume (0.0025, 0.0031, and 0.0028 µm3, respectively) and in glomerulosclerosis (18%, 7%, and 11%, respectively). There was a marked increase in glomerulosclerosis with age in the superficial region, but larger glomerular volume was not associated with age at any cortical depth. Glomerulosclerosis associated more strongly with arteriosclerosis and ischemic-appearing glomeruli in the superficial region. Hypertension, lower eGFR, and interstitial fibrosis associated with glomerulosclerosis and glomerular volume to a similar extent at any depth. Diabetes and proteinuria more strongly associated with glomerulosclerosis in the deep and middle regions, respectively, but neither associated with glomerular volume differently by depth. Obesity associated more strongly with glomerular volume in the superficial cortex. Conclusions Most clinical characteristic show similar associations with glomerulosclerosis and glomerulo-megaly at different cortical depths. Exceptions include age-related glomerulosclerosis, which appears to be an ischemic process and is more predominant in the superficial region.
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U2 - 10.1681/ASN.2019020183
DO - 10.1681/ASN.2019020183
M3 - Article
C2 - 31278193
AN - SCOPUS:85070848255
VL - 30
SP - 1471
EP - 1480
JO - Journal of the American Society of Nephrology : JASN
JF - Journal of the American Society of Nephrology : JASN
SN - 1046-6673
IS - 8
ER -