Set-up of a Platform for Personalized Diagnosis of Rare Kidney Diseases (NIKE)

Summary

Chronic kidney disease (CKD) is a major health problem, with steadily increasing incidence and prevalence and the threat of a true "epidemic". Converging evidence suggests a high prevalence of genetic etiology in rare kidney diseases and the list of new disease-causing genes is constantly updated. Recent advances in next-generation sequencing (NGS) technologies have prompted a significant improvement in the diagnosis of rare kidney diseases. Notwithstanding this, NGS generates high numbers of information that need to be properly analysed by the joint efforts of geneticists, nephrologists and bioinformatics in order to integrate clinical and genetic information in a personalized manner. In addition, in selected cases, the contribution of researchers proves essential for the development of experimental models of the disease to study and understand the pathogenic features and propose a personalized therapeutic approach. Such an innovative, integrated diagnostic paradigm is currently available in few centers all over the world and cannot be easily translated in daily clinical practice.

The aim of the study is to set-up an integrated diagnostic algorithm to extend the newest personalized diagnostic and treatment strategies for rare kidney diseases to all patients in the Tuscany region, under 40 years of age with kidney disease. This algorithm will be based on a constant cross-talk between participating centers and a dedicated multidisciplinary team. Diagnostic and therapeutic performances will be validated at European level.

Conditions

• Chronic Kidney Diseases

Interventions

DIAGNOSTIC_TEST

Conclusive genetic testing

Patients will be referred for genetic counseling at the study coordinating center. This will lead to a conclusive genetic diagnosis.

DIAGNOSTIC_TEST

Genotype-phenotype correlation for personalized diagnosis

Patients and their family members will undergo a thorough clinical reassessment at the study coordinating center to identify diagnostic handles of the suspected disease based on the genetic test result (reverse phenotyping). The clinical reassessment could include the performance of additional clinical and instrumental tests, as well as other specialized consultations. This will lead to a conclusive genetic diagnosis in a substantial proportion of cases, cases, who will then be provided with genetic counselling.

DIAGNOSTIC_TEST

Personalized study of variants of uncertain clinical significance (VUS) through functional studies on 3D organ-on-a-chip

The investigators will perform functional assessment trough urine derived Renal Progenitor Cells (u-RPC) to establish the role of variants in determining the clinical phenotype.

Sponsors & Collaborators

• Meyer Children's Hospital IRCCS

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

40 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-07-09

Primary Completion

2023-06-27

Completion

2024-06-30

Countries

• Italy

Study Locations