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Abstract
IntroductionChildhood-onset nephrotic syndrome has a variable clinical course. Improved predictive markers of long-term outcomes in children with nephrotic syndrome are needed. This study tests the association between baseline urinary epidermal growth factor (uEGF) excretion and longitudinal kidney function in children with nephrotic syndrome.MethodsThe study evaluated 191 participants younger than 18 years enrolled in the Nephrotic Syndrome Study Network, including 118 with their first clinically indicated kidney biopsy (68 minimal change disease; 50 focal segmental glomerulosclerosis) and 73 with incident nephrotic syndrome without a biopsy. uEGF was measured at baseline for all participants and normalized by the urine creatinine (Cr) concentration. Renal epidermal growth factor (EGF) mRNA was measured in the tubular compartment microdissected from kidney biopsy cores from a subset of patients. Linear mixed models were used to test if baseline uEGF/Cr and EGF mRNA expression were associated with change in estimated glomerular filtration rate (eGFR) over time.ResultsHigher uEGF/Cr at baseline was associated with slower eGFR decline during follow-up (median follow-up = 30 months). Halving of uEGF/Cr was associated with a decrease in eGFR slope of 2.0 ml/min per 1.73 m2 per year (P < 0.001) adjusted for age, race, diagnosis, baseline eGFR and proteinuria, and APOL1 genotype. In the biopsied subgroup, uEGF/Cr was correlated with EGF mRNA expression (r = 0.74; P < 0.001), but uEGF/Cr was retained over mRNA expression as the stronger predictor of eGFR slope after multivariable adjustment (decrease in eGFR slope of 1.7 ml/min per 1.73 m2 per year per log2 decrease in uEGF/Cr; P < 0.001).ConclusionuEGF/Cr may be a useful noninvasive biomarker that can assist in predicting the long-term course of kidney function in children with incident nephrotic syndrome.
Highlights
Childhood-onset nephrotic syndrome has a variable clinical course
The study evaluated 191 participants younger than 18 years enrolled in the Nephrotic Syndrome Study Network, including 118 with their first clinically indicated kidney biopsy (68 minimal change disease; 50 focal segmental glomerulosclerosis) and 73 with incident nephrotic syndrome without a biopsy. urinary epidermal growth factor (uEGF) was measured at baseline for all participants and normalized by the urine creatinine (Cr) concentration
UEGF/Cr was correlated with epidermal growth factor (EGF) mRNA expression (r 1⁄4 0.74; P < 0.001), but uEGF/Cr was retained over mRNA expression as the stronger predictor of estimated glomerular filtration rate (eGFR) slope after multivariable adjustment
Summary
The study evaluated 191 participants younger than 18 years enrolled in the Nephrotic Syndrome Study Network, including 118 with their first clinically indicated kidney biopsy (68 minimal change disease; 50 focal segmental glomerulosclerosis) and 73 with incident nephrotic syndrome without a biopsy. uEGF was measured at baseline for all participants and normalized by the urine creatinine (Cr) concentration. The study evaluated 191 participants younger than 18 years enrolled in the Nephrotic Syndrome Study Network, including 118 with their first clinically indicated kidney biopsy (68 minimal change disease; 50 focal segmental glomerulosclerosis) and 73 with incident nephrotic syndrome without a biopsy. The study includes 2 cohorts: an incident, nonbiopsy childhood-onset nephrotic syndrome (CO-NS) cohort and a biopsy cohort. The study visit schedule includes a baseline assessment within 45 days of onset of CO-NS nonbiopsied children or within 45 days of the kidney biopsy for biopsied children. All enrolled participants are subsequently followed every 6 months For this analysis, we excluded participants older than 18 years at the baseline visit; those with a biopsy diagnosis other than MCD, FSGS, or CO-NS; and those who did not have a baseline uEGF measurement. Institutional review board approval for this study was obtained at all participating sites with appropriate consent and assent forms
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