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

Meyer Children's Hospital IRCCS

Status: Active, not recruiting

Conditions: Chronic Kidney Diseases

Treatments: Diagnostic Test: Conclusive genetic testing; Diagnostic Test: Genotype-phenotype correlation for personalized diagnosis; Diagnostic Test: Personalized study of variants of uncertain clinical significance (VUS) through functional studies on 3D organ-on-a-chip

Study type: Interventional

Funder types: Other

Identifiers

NCT06325072

NIKE

Details and patient eligibility

About

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.

Enrollment: 160 estimated patients

Sex: All

Ages: Under 40 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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160 participants in 3 patient groups

Pathogenic variants

Experimental group

Description:

Variants fitting bioinformatic prioritization criteria for pathogenicity according to ACMG guidelines and the clinical phenotype, and variants already reported in the literature will be defined as pathogenic variants

Treatment:

Diagnostic Test: Conclusive genetic testing

Potentially Pathogenic Variants

Experimental group

Description:

Variants fitting bioinformatic prioritization criteria but apparently do not correlate with the clinical phenotype and have not been previously reported in the literature will be defined as potentially pathogenic variants

Treatment:

Diagnostic Test: Genotype-phenotype correlation for personalized diagnosis

Variants of Unknown Significance (VUS)

Experimental group

Description:

Variants fitting the phenotype but not fitting bioinformatic prioritization criteria will be defined as variants of uncertain clinical significance (VUS)

Treatment:

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