Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multidisciplinary approach

Abstract

The Nephrotic Syndrome Study Network (NEPTUNE) is a North American multi-center collaborative consortium established to develop a translational research infrastructure for Nephrotic Syndrome. This includes a longitudinal observational cohort study, a pilot and ancillary studies program, a training program, and a patient contact registry. NEPTUNE will enroll 450 adults and children with minimal change disease, focal segmental glomerulosclerosis and membranous nephropathy for detailed clinical, histopathologic, and molecular phenotyping at the time of clinically-indicated renal biopsy. Initial visits will include an extensive clinical history, physical examination, collection of urine, blood and renal tissue samples, and assessments of quality of life and patient-reported outcomes. Follow-up history, physical measures, urine and blood samples, and questionnaires will be obtained every 4 months in the first year and bi-annually, thereafter. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and digitalized histologic data for comprehensive analyses using systems biology approaches. Analytical strategies were designed to transform descriptive information to mechanistic disease classification for Nephrotic Syndrome and to identify clinical, histological, and genomic disease predictors. Thus, understanding the complexity of the disease pathogenesis will guide further investigation for targeted therapeutic strategies.

Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management

“…It is possible that our clinical inclusion criteria excluded some patients who would be found to have a monogenic disease caused by one of the NS genes so far reported, but we estimated that this would be unlikely. For example the NEPTUNE study included patients with diseases that we excluded, such as IgA nephropathy, membranous nephropathy and secondary FSGS, and found no patients in those subgroups with (SRNS) monogenic disease 17 .…”

Defining cell-type specificity at the transcriptional level in human disease

“…Black line indicates the correlation of PCOLCE2 mRNA level with GFR. group in a rare disease cohort (Halbritter et al 2012;Gadegbeku et al 2013).…”

Optimizing Enrollment of Patients into Nephrology Research Studies

“…The NEPTUNE (NEPTUNE-study.org) is one of these rare disease networks that launched in 2010 to bring a systems biology approach to redefining the conditions leading to nephrotic syndrome from phenotypic, molecular, and genetic bases (12). The network was established with 22 academic partners, including internal medicine and pediatric nephrology programs, pathologists, and patient and research advocacy foundations.…”