TY - JOUR
T1 - Global glomerulosclerosis with nephrotic syndrome; the clinical importance of age adjustment
AU - Hommos, Musab S.
AU - Zeng, Caihong
AU - Liu, Zhihong
AU - Troost, Jonathan P.
AU - Rosenberg, Avi Z.
AU - Palmer, Matthew
AU - Kremers, Walter K.
AU - Cornell, Lynn D.
AU - Fervenza, Fernando C.
AU - Barisoni, Laura
AU - Rule, Andrew D.
N1 - Funding Information:
This study was supported with funding from the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK090358) and the National Center for Advancing Translational Sciences (NCATS) (CTSA Grant UL1 TR000135). The Nephrotic Syndrome Study Network Consortium (NEPTUNE), U54-DK-083912, is a part of the NIH Rare Disease Clinical Research Network (RDCRN), supported through a collaboration between the Office of Rare Diseases Research (ORDR), NCATS, and the National Institute of Diabetes, Digestive, and Kidney Diseases. Additional funding and/or programmatic support for this project has also been provided by the University of Michigan, the NephCure Kidney International, and the Halpin Foundation. China DiKiP is supported by the National Natural Science Foundation of China (No. 81570644), the National Key Technology R&D Program (2015BAI12B05), and the National Key Research and Development Program of China (2016YFC0904100).
Publisher Copyright:
© 2017 International Society of Nephrology
PY - 2018/5
Y1 - 2018/5
N2 - Globally sclerotic glomeruli (GSG) occur with both normal aging and kidney disease. However, it is unknown whether any GSG or only GSG exceeding that expected for age is clinically important. To evaluate this, we identified patients with a glomerulopathy that often presents with nephrotic syndrome (focal segmental glomerulosclerosis, membranous nephropathy, or minimal change disease) in the setting of the Nephrotic Syndrome Study Network (NEPTUNE), China-Digital Kidney Pathology (DiKiP), and the Southeast Minnesota cohorts. Age-based thresholds (95th percentile) for GSG based on normotensive living kidney donors were used to classify each patient into one of three groups; no GSG, GSG normal for age, or GSG abnormal for age. The risk of end-stage renal disease or a 40% decline in glomerular filtration rate during follow-up was then compared between groups. Among the 425 patients studied, 170 had no GSG, 107 had GSG normal for age, and 148 had GSG abnormal for age. Compared to those with no GSG, the risk of kidney disease progression with GSG normal for age was similar but was significantly higher with GSG abnormal for age. This increased risk with GSG abnormal for age remained significant after adjustment for interstitial fibrosis, arteriosclerosis, age, hypertension, diabetes, body mass index, glomerulopathy type, glomerular filtration rate, and proteinuria. Thus, in patients with glomerulopathy that often presents with nephrotic syndrome, global glomerulosclerosis is clinically important only if it exceeds that expected for age.
AB - Globally sclerotic glomeruli (GSG) occur with both normal aging and kidney disease. However, it is unknown whether any GSG or only GSG exceeding that expected for age is clinically important. To evaluate this, we identified patients with a glomerulopathy that often presents with nephrotic syndrome (focal segmental glomerulosclerosis, membranous nephropathy, or minimal change disease) in the setting of the Nephrotic Syndrome Study Network (NEPTUNE), China-Digital Kidney Pathology (DiKiP), and the Southeast Minnesota cohorts. Age-based thresholds (95th percentile) for GSG based on normotensive living kidney donors were used to classify each patient into one of three groups; no GSG, GSG normal for age, or GSG abnormal for age. The risk of end-stage renal disease or a 40% decline in glomerular filtration rate during follow-up was then compared between groups. Among the 425 patients studied, 170 had no GSG, 107 had GSG normal for age, and 148 had GSG abnormal for age. Compared to those with no GSG, the risk of kidney disease progression with GSG normal for age was similar but was significantly higher with GSG abnormal for age. This increased risk with GSG abnormal for age remained significant after adjustment for interstitial fibrosis, arteriosclerosis, age, hypertension, diabetes, body mass index, glomerulopathy type, glomerular filtration rate, and proteinuria. Thus, in patients with glomerulopathy that often presents with nephrotic syndrome, global glomerulosclerosis is clinically important only if it exceeds that expected for age.
KW - FSGS
KW - age-based threshold
KW - global glomerulosclerosis
KW - membranous nephropathy
KW - minimal change disease
KW - nephrotic syndrome
UR - http://www.scopus.com/inward/record.url?scp=85038879758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038879758&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2017.09.028
DO - 10.1016/j.kint.2017.09.028
M3 - Article
C2 - 29273332
AN - SCOPUS:85038879758
SN - 0085-2538
VL - 93
SP - 1175
EP - 1182
JO - Kidney international
JF - Kidney international
IS - 5
ER -