TY - JOUR
T1 - Larger nephron size and nephrosclerosis predict progressive ckd and mortality after radical nephrectomy for tumor and independent of kidney function
AU - Denic, Aleksandar
AU - Elsherbiny, Hisham
AU - Mullan, Aidan F.
AU - Leibovich, Bradley C.
AU - Houston Thompson, R.
AU - Archila, Luisa Ricaurte
AU - Narasimhan, Ramya
AU - Kremers, Walter K.
AU - Alexander, Mariam P.
AU - Lieske, John C.
AU - Lerman, Lilach O.
AU - Rule, Andrew D.
N1 - Funding Information:
This study was supported with funding from National Institute of Diabetes and Digestive and Kidney Diseases grant R01 DK090358. A. Denic was supported by the Robert W. Fulk Career Development Award Fund in Nephrology Research. W. Kremers reports grants from the National Institutes of Health, during the conduct of the study. L. Lerman reports grants from the National Institute of Diabetes and Digestive and Kidney Diseases, during the conduct of the study. A. Rule reports grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, during the conduct of the study.
Funding Information:
W. Kremers reports grants from AstraZeneca, Biogen, and Roche, outside the submitted work. L. Lerman reports personal fees from AstraZeneca, grants from Novo Nordisk, and personal fees and nonfinancial support from Weijian Technologies, outside the submitted work. J. Lieske reports grants and other from Alnylam and Dicerna; grants from Allena, OxThera, Retrophin, and Siemens; and other from Novobiome, Orfan, and Synlogic, outside the submitted work.
Publisher Copyright:
Copyright © 2020 by the American Society of Nephrology
PY - 2020/11
Y1 - 2020/11
N2 - Background Nephron hypertrophy and nephrosclerosis may be important determinants of CKD and mortality. However, studies of outcomes associated with these microstructural features have been limited to small tissue specimens from patients selected for either good kidney health or known kidney disease. Methods To determine whether microstructural features are predictive of progressive CKD and mortality outcomes, we studied patients who underwent a radical nephrectomy for a tumor. Large wedge sections of renal parenchyma distal to the tumor were stained and scanned into high-resolution images; we annotated the cortex and all glomeruli to calculate glomerular volume, cortex volume per glomerulus, and percentage of globally sclerotic glomeruli. Morphometric measurements also included percentages of artery luminal stenosis and interstitial fibrosis/tubular atrophy (IF/TA) of the cortex. At follow-up visits every 6-12 months, we determined which patients experienced progressive CKD (defined as dialysis, kidney transplantation, or a 40% decline from postnephrectomy eGFR). Cox models for these outcomes were adjusted for age, sex, body mass index, hypertension, diabetes, smoking, eGFR, and proteinuria. Results Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73 m2), 117 progressive CKD events, 183 noncancer deaths, and 116 cancer deaths occurred during a median follow-up of 6.4 years. Larger glomerular volume, larger cortex per glomerulus, and higher percentage of globally sclerotic glomeruli or IF/TA predicted progressive CKD. Higher percentage IF/TA also predicted noncancer mortality. Microstructural features did not predict cancer mortality or recurrence. Conclusions After a radical nephrectomy, larger nephrons and nephrosclerosis predicted progressive CKD, and IF/TA predicted noncancer mortality. Morphometric analysis of renal parenchyma can predict noncancer clinical events in patients long after their radical nephrectomy.
AB - Background Nephron hypertrophy and nephrosclerosis may be important determinants of CKD and mortality. However, studies of outcomes associated with these microstructural features have been limited to small tissue specimens from patients selected for either good kidney health or known kidney disease. Methods To determine whether microstructural features are predictive of progressive CKD and mortality outcomes, we studied patients who underwent a radical nephrectomy for a tumor. Large wedge sections of renal parenchyma distal to the tumor were stained and scanned into high-resolution images; we annotated the cortex and all glomeruli to calculate glomerular volume, cortex volume per glomerulus, and percentage of globally sclerotic glomeruli. Morphometric measurements also included percentages of artery luminal stenosis and interstitial fibrosis/tubular atrophy (IF/TA) of the cortex. At follow-up visits every 6-12 months, we determined which patients experienced progressive CKD (defined as dialysis, kidney transplantation, or a 40% decline from postnephrectomy eGFR). Cox models for these outcomes were adjusted for age, sex, body mass index, hypertension, diabetes, smoking, eGFR, and proteinuria. Results Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73 m2), 117 progressive CKD events, 183 noncancer deaths, and 116 cancer deaths occurred during a median follow-up of 6.4 years. Larger glomerular volume, larger cortex per glomerulus, and higher percentage of globally sclerotic glomeruli or IF/TA predicted progressive CKD. Higher percentage IF/TA also predicted noncancer mortality. Microstructural features did not predict cancer mortality or recurrence. Conclusions After a radical nephrectomy, larger nephrons and nephrosclerosis predicted progressive CKD, and IF/TA predicted noncancer mortality. Morphometric analysis of renal parenchyma can predict noncancer clinical events in patients long after their radical nephrectomy.
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U2 - 10.1681/ASN.2020040449
DO - 10.1681/ASN.2020040449
M3 - Article
C2 - 32938650
AN - SCOPUS:85094982519
SN - 1046-6673
VL - 31
SP - 2642
EP - 2652
JO - Journal of the American Society of Nephrology : JASN
JF - Journal of the American Society of Nephrology : JASN
IS - 11
ER -