Project: Implementation of personalised management in nephrotic syndrome

Acronym	PER-NEPH (Reference Number: ERAPERMED2021-207)
Duration	01/04/2022 - 01/04/2025
Project Topic	Nephrotic syndrome in children and young adults is a frequent medical problem of very diverse pathophysiology and prognosis. Current diagnostic algorithms fail to avoid under- and overtreatment of patients with toxic drugs as defining the underlying cause is frequently difficult. We have developed a diagnostic algorithm of stratifying patients through advanced genetic testing, reverse phenotyping, and personalised disease models. This can double the current diagnostic rate in patients not responding to first line therapy and to predict disease relapse in those that progress to end stage kidney disease and have to undergo kidney transplant. The aims of this project are to: 1. Implementation of this diagnostic algorithm in selected European sites by a) selecting patients for a personalised genetic diagnosis, b) whole exome sequencing and bioinformatic prioritization of potentially pathogenic variants, c) validating genotype-phenotype correlation for a personalised diagnosis, and d) personalising the assessment of variants of unknown significance by functional studies with patient urine-derived renal progenitors and 3D organ-on-a-chip disease models. 2. Personalising the assessment of non-genetic forms and of relapse after transplant by a) identifying patients negative to the genetic testing, b) assessing patients with proteinuria relapse after kidney transplant, c) personalising the detection of immunologic factors by using STED super-resolution microscopy and d) personalising the detection of circulatory permeability factors by using a 3D organ-on-a-chip model system. 3. Assessing the cost-effectiveness as well as clinical, ethical, and legal consequences of the proposed algorithm by a) a multicentre model-based cost-utility analysis of the proposed algorithm and by assessing the b) clinical, c) ethical, and d) legal consequences in close conjunction with the study participants and the respective patient organisations by standardised questionnaire tools.
Network	ERA PerMed
Call	4th Joint Transnational Call for Proposals (2021)

Project partner

Number	Name	Role	Country
1	Meyer Children's Hospital	Coordinator	Italy
2	University of Florence	Partner	Italy
3	Bellvitge Biomedical Research Institute (IDIBELL)	Partner	Spain
4	University Hospital of the Ludwig-Maximilians University Munich (LMU Klinikum)	Partner	Germany