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 study is a prospective, observational study that enrolls children and adults with MCD, FSGS, and MN. 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 (MCD, FSGS, or 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. NEPTUNE provides high-resolution clinical phenotypes of participants which are related to genome wide analyses to molecularly define disease categories, outcome predictors, and therapeutic targets. Molecular profiles and gene expression data are linked to phenotypic, genetic, and histologic data for systems biology analysis.

The primary objective is to investigate the underlying disease mechanisms, elucidate pathogenesis, and identify therapeutic targets for clinical trials.

The primary outcome measure 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 is also evaluated, defined as a 25 mL/min/1.73 m2 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 ≤ 10 cc/min, initiation of maintenance dialysis or preemptive kidney transplantation.

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

• Adults and children with a diagnosis of MCD, FSGS, or MN, or with an incipient diagnosis of these syndromes
• Have a proteinuria ≥ 1,500 mg/day, estimated from a 24-hour or protein to creatinine ratio urine collection
• Sub-nephrotic proteinuria allowed to capture the broad spectrum of clinical presentation

• Prior solid organ transplant
• Clinical diagnosis of glomerulopathy without diagnostic renal biopsy
• Clinical, serological, or histological evidence of systemic lupus erythematosus (SLE)
• Clinical or histological evidence of other renal diseases
• Known systemic disease diagnosis at time of enrollment with a life expectancy less than 6 months

This study is ongoing.