Clinical trial NCT06325072: Set-up of a Platform for Personalized Diagnosis of Rare Kidney Diseases (NIKE)
Official title: Set-up of a Platform for Personalized Diagnosis of Rare Kidney Diseases (NIKE)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Chronic Kidney Diseases
Lead sponsor: Meyer Children's Hospital IRCCS
Sponsor class: OTHER
First posted: 2024-03-22
Enrollment: 160
Sex: ALL
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients selected based on the inclusion criteria will be evaluated by a multidisciplinary team of experts. All the selected patients will undergo genetic testing by clinical exome sequencing and in silico filtering for a panel of genes described as causing or in association with CKD. Identified variants will be classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Reverse phenotyping will be performed according to the results of genetic testing. The results of the diagnostic work-up will be evaluated by a multi-disciplinary team of experts in order to establish conclusive diagnosis.
Primary purpose: DIAGNOSTIC

Brief 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.


Eligibility criteria: Inclusion Criteria:

* family history of kidney disease and/or parental consanguinity;
* extra-renal involvement (e.g., sensorineural hearing loss);
* resistance to treatment (e.g., immunosuppressive);
* metabolic acidosis or metabolic alkalosis in the absence of renal failure;
* ultrasound detection of of at least 2 cystic lesions in each kidney or nephrocalcinosis;
* ultrasound detection of congenital abnormalities of the kidney and urinary tract (CAKUT) and CKD stage ≥ 2 according to KDIGO definition
* informed consent form.

Exclusion Criteria:

* age \> 40
* refuse to participate to the study

Primary outcomes:
measure: Validation of genetic diagnosis
timeFrame: From enrollment (genetic testing) until the date of returning of genetic testing results (up to 6 months)
Secondary outcomes:
measure: Identification of molecular pathways
timeFrame: From enrollment (genetic testing) until the last patient last visit, estimated up to 12 months
measure: Explore the applicability of gene editing in rare kidney diseases
timeFrame: From enrollment (genetic testing) until the last patient last visit, estimated up to 12 months
Other outcomes:
Locations:
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Firenze
country: Italy
facility: Meyer Children's Hospital IRCCS
city: Firenze
country: Italy
facility: USL Toscana Centro
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
Study officials:
References: