Nephrotic Syndrome Study Network (NEPTUNE)

General Description

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 phs003210.v1.p1. The RNAseq data generated can be accessed through GEO, accession numbers GSE219185 and GSE197307.

This study is ongoing.

Objectives

The NEPTUNE observational study was established to investigate the underlying disease mechanisms, elucidate pathogenesis, and identify therapeutic targets for clinical trials.

Outcome Measure

The primary outcome is a composite measure of change in urinary protein excretion and change in renal function, which is defined as remission, partial remission, and non-remission. The rate of change of renal function will also be evaluated, defined as a 25 mL/min/1.73m2 reduction in follow-up estimated GFR (eGFR) compared to baseline eGFR; 50% decline in follow-up eGFR compared to baseline measurement; and ESRD defined as eGFR ≤ 10cc/min, initiation of maintenance dialysis or preemptive kidney transplantation

Secondary outcome measures include quality of life assessment, development of new-onset diabetes, malignancies, infections, thromboembolic events, hospitalization, acute kidney injury, and death.

Criteria

Adults and children with a diagnosis of FSGS, MCD, or MN or with an incipient diagnosis of these syndromes are eligible for the study. Individuals must have a proteinuria ≥ 500 mg/day, estimated from a 24 hour or protein to creatinine ratio urine collection, to participate. Patients with sub-nephrotic proteinuria are included to capture the broad spectrum of clinical presentation.

Exclusion criteria are documented in the study protocol.

Outcome

This study is ongoing.