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Comparative Study
. 2018 May;93(5):1175-1182.
doi: 10.1016/j.kint.2017.09.028. Epub 2017 Dec 19.

Global glomerulosclerosis with nephrotic syndrome; the clinical importance of age adjustment

Musab S Hommos  1 , Caihong Zeng  2 , Zhihong Liu  2 , Jonathan P Troost  3 , Avi Z Rosenberg  4 , Matthew Palmer  5 , Walter K Kremers  6 , Lynn D Cornell  7 , Fernando C Fervenza  1 , Laura Barisoni  8 , Andrew D Rule  9
Affiliations
Comparative Study

Global glomerulosclerosis with nephrotic syndrome; the clinical importance of age adjustment

Musab S Hommos et al. Kidney Int. 2018 May.

Abstract

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.

Keywords: FSGS; age-based threshold; global glomerulosclerosis; membranous nephropathy; minimal change disease; nephrotic syndrome.

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Conflict of interest statement

DISCLOSURE

Authors declare no conflict in financial interest.

Figures

Figure 1
Figure 1. Study sample
FSGS: focal segmental glomerulosclerosis. MN: membranous nephropathy. MCD: minimal change disease. ESRD: end-stage renal disease. GSG: globally sclerotic glomeruli
Figure 2
Figure 2. Distribution of % globally sclerotic glomeruli (GSG) for patients with focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or minimal change disease (MCD) and any GSG on biopsy
The % globally sclerotic glomeruli (GSG) substantially overlap between patients with GSG normal for age and patients with GSG abnormal for age. There was 60% overlap for FSGS, 94% overlap for MN, and 73% overlap for MCD. Patients with no GSG (27% of FSGS, 43% of MN, and 77% of MCD) are not shown.
Figure 3
Figure 3. Cumulative incidence of ESRD or 40% decline in eGFR
There was no evident difference in risk of this outcome between patients with GSG normal for age and patients with no GSG (log-rank p-value 0.98). Patients with GSG abnormal for age had significant increase in this outcome compared to other patients (log-rank p-value <.0001). The risk at 5 years and beyond is determined by the SE Minnesota cohort.
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