for Physicians
for Patients

Research Project

Project Title:

NEPHrotic syndrome from childhood to adulthood: creating a NETwork for research and care. The NEPHNET project

Project Type:

 Translational research

Disease group(s):

 Immune glomerulopathies

Project Summary:

 Renal glomerulopathies represent a group of rare kidney diseases affecting the glomerular filtration barrier (GFB). Damage to the GFB leads to urinary protein loss and, in severe cases, to nephrotic syndrome, characterized by edema, massive proteinuria and hypoalbuminemia. Causes can be genetic, immune-mediated or undetermined, i.e., idiopathic. Despite its rarity, idiopathic nephrotic syndrome (NS) represents the most frequent glomerular disease in children. Its onset can be at any age, though typically it occurs at 2-6 years of age, less frequently in adults. In children, diagnosis is based on clinical presentation and response to a standard course of oral prednisone, which distinguish between steroid-sensitive (SSNS) and
steroid-resistant (SRNS) forms. In adults, a renal biopsy is performed at onset to discriminate between glomerulopathies with a similar clinical presentation and shows minimal changes or focal segmental glomerulosclerosis (FSGS) in a minority of cases. Etiology is clear only in monogenic forms, which represent approximately 66% of congenital and infantile cases, 30% of children and 10-15% of young adults. A correct identification of these forms has crucial implications for management, as monogenic forms respond poorly to immunosuppressive treatment and do not relapse following renal transplantation. On the
contrary, so-called "idiopathic" forms present an extremely heterogeneous natural history that, especially in children and adults with FSGS, can recur after renal transplant.
Research aimed at etiology-based characterization and treatment has been performed mainly in children, while in adult nephrology centers these patients, representing a small quota of patient population, are often overlooked and misdiagnosed. The number of young patients graduating from pediatric to adult renal care has progressively increased due to improved management resulting in patient survival rates of 85-90% and adult renal services are exposed to an increasing number of young adult patients who have either transitioned from pediatric care or presented directly to adult services. To date, while it is known that 10-15% of pediatric forms of SSNS persist beyond puberty, their adult outcome is uncertain and their
management not evidence-based, also due to the lack of consistent research data.
Our project aims to bridge this gap by creating the first Italian network specific for glomerular diseases determining nephrotic syndrome at all ages - NEPHNET - comprising the two major pediatric and two adult nephrology centers acting as hubs reaching out to all Italian centers through a partnership with SIN (Società Italiana di Nefrologia). Thank to this network, consistent clinical data will be collected in a dedicated patient registry and biological samples will be stored in three different biobanks, two for pediatric and one for adult patients, providing an integrated platform for high-quality clinical and research studies and for efficient transition of children to adult centers. This platform will also implement innovative multiomics
techniques in order to develop integrated risk prediction models for the progression of rare glomerular diseases from childhood to adulthood and will be accessible for future studies. The ultimate goal of this project is to improve clinical management of rare glomerular diseases at all ages.

Lead principal investigator(s):

 Marina Vivarelli, Rome

Co-investigator(s):

 Giuseppe Grandaliano, Rome

Project Period:

 04/2023   -   04/2025

Sponsors:

 National funding agency
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