Redefining Nephrotic Syndrome in Molecular Terms: Outcome-associated molecular clusters and patient stratification with noninvasive surrogate biomarkers
Author:
Mariani Laura H., Eddy SeanORCID, Martini Sebastian, Eichinger Felix, Godfrey Brad, Nair Viji, Adler Sharon G., Appel Gerry B., Athavale Ambarish, Barisoni Laura, Brown Elizabeth, Cattran Dan C., Dell Katherine M., Derebail Vimal, Fervenza Fernando C., Fornoni Alessia, Gadegbeku Crystal A., Gibson Keisha L., Gipson Deb, Greenbaum Lawrence A., Hingorani Sangeeta R., Hlandunewich Michelle A., Hogan John, Holzman Larry B., Jefferson J. Ashley, Kaskel Frederick J., Kopp Jeffrey B., Lafayette Richard A., Lemley Kevin V., Lieske John C., Lin Jen-Jar, Myers Kevin E., Nachman Patrick H., Nast Cindy C., Neu Alicia M., Reich Heather N., Sambandam Kamal, Sedor John R., Sethna Christine B., Srivastava Tarak, Trachtman Howard, Tran Cheryl, Wang Chia-shi, Kretzler Matthias
Abstract
SummaryA tissue transcriptome driven classification of nephrotic syndrome patients identified a high risk group of patients with TNF activation and established a non-invasive marker panel for pathway activity assessment paving the way towards precision medicine trials in NS.AbstractNephrotic syndrome from primary glomerular diseases can lead to chronic kidney disease (CKD) and/or end-stage renal disease (ESRD). Conventional diagnoses using a combination of clinical presentation and descriptive biopsy information do not accurately predict risk for progression in patients with nephrotic syndrome, which complicates disease management. To address this challenge, a transcriptome-driven approach was used to classify patients with minimal change disease and focal segmental glomerulosclerosis in the Nephrotic Syndrome Study Network (NEPTUNE). Transcriptome-based classification revealed a group of patients at risk for disease progression. High risk patients had a transcriptome profile consistent with TNF activation. Non-invasive urine biomarkers TIMP1 and CCL2 (MCP1), which are causally downstream of TNF, accurately predicted TNF activation in the NEPTUNE cohort setting the stage for patient stratification approaches and precision medicine in kidney disease.
Publisher
Cold Spring Harbor Laboratory
Cited by
7 articles.
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