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 multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This includes a longitudinal observational cohort study, a pilot and ancillary study 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, histopathological, 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 biannually, thereafter. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and digitalized histological 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.

Figure 1. NEPTUNE Cohort Study Design

Figure 2. Overview of Multilevel Data Integration in NEPTUNE

“The integrative analytical approach in NEPTUNE relies on obtaining comprehensive molecular and clinical information from each subject. For molecular analysis, the initial step is to generate large-scale datasets of genome-wide genetic variation and targeted gene sequencing, compartment specific gene expression data on renal biopsy tissue, leukocytes and urine, and proteomic/metabolomic data from both urine and blood samples. Each molecular dataset will be interrogated alone and in relationship with the others in order to understand multidimensional molecular interactions. In addition, the molecular data will be analyzed with the comprehensive clinical information to determine associations between molecular events and clinical outcomes. The overall goal is to develop a framework for studies to define the molecular heterogeneity of NS for disease stratification, biomarker identification and molecular target definition. (Figure modified from Keller et al).”