Nephrotic Syndrome Study Network

Pro non-inflammatory glomerular diseases, including minimal change disease (MCD), focal and segmental glomerulosclerosis (FSGS) and membranous nephropathy (MN), account for approximately 15% of prevalent end-stage renal disease (ESRD) cases in the United States. Development of successful therapeutic interventions is hindered by a limited knowledge of underlying glomerular disease mechanisms. In response to the need for research concerning these conditions, the Nephrotic Syndrome Study Network (NEPTUNE) was established to investigate the underlying disease mechanisms, elucidate pathogenesis, and identify therapeutic targets for clinical trials.

The NEPTUNE cohort study, one of the projects initiated by the consortium, is a prospective, observational study that enrolls children and adults with FSGS, MCD, and MN. In the first funding cycle, NEPTUNE recruited more than 500 rigorously phenotyped NS participants. In the second funding cycle, NEPTUNE will add 150 adults with NS at the time of diagnostic kidney biopsy enriched for individuals at high risk for adverse health outcomes (African ancestry and proteinuria >1.5 gm/day) and 120 children with NS at presentation and prior to biopsy. These cohorts will add critical segments of NS disease phenotypes to reflect the full NS disease spectrum in NEPTUNE.

At baseline, NEPTUNE collects information on demographics, clinical history, physical examination, as well as tissue samples from a renal biopsy visit, blood and urine samples. Questionnaires are given to assess quality of life and self-reported health. Participants are assigned into a specific study cohort (FSGS, MCD, MN) based on renal biopsy. After baseline assessment is complete, participants are followed over 30 months to collect data concerning health, quality of life, and outcomes, and urine and blood samples. The NEPTUNE consortium banks the long-term observational data and corresponding biological specimens for future studies. NEPTUNE provides high-resolution clinical phenotypes of patients which are related to genome wide analyses to molecularly define disease categories, outcome predictors and therapeutic targets. The primary outcome is a composite measure of change in urinary protein excretion and change in renal function. Secondary outcome measures include quality of life assessment, development of new-onset diabetes, malignancies, infections, thromboembolic events, hospitalization, acute kidney injury, and death. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and histologic data for systems biology analysis.

The whole genome sequencing (WGS) data generated from the NEPTUNE study can be accessed through dbGaP, accession number <a href = "https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs003210.v1.p1" target="_blank" rel="noopener noreferrer">phs003210.v1.p1</a>. The RNAseq data generated can be accessed through GEO, accession numbers <a href = "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE219185" target="_blank" rel="noopener noreferrer">GSE219185</a> and <a href = "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197307" target="_blank" rel="noopener noreferrer">GSE197307</a>.

This study is ongoing.