Set-up of a Platform for Personalized Diagnosis of Rare Kidney Diseases (NIKE)
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Chronic Kidney Diseases
- Sponsor
- Meyer Children's Hospital IRCCS
- Enrollment
- 160
- Locations
- 4
- Primary Endpoint
- Validation of genetic diagnosis
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
Paola Romagnani
MD
Meyer Children's Hospital IRCCS
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
Outcomes
Primary Outcomes
Validation of genetic diagnosis
Time Frame: From enrollment (genetic testing) until the date of returning of genetic testing results (up to 6 months)
The investigators will assess the role of potentially pathogenic variants and variants of uncertain clinical significance (VUS) in determining a conclusive genetic diagnosis by patient reassessment (reverse phenotyping) or in vitro functional studies. In detail, after the results of ES, a multidisciplinary team will evaluate the results of sequencing and will eventually request additional investigations (e.g., laboratory or imaging tests, specific consultations, etc) to the patient and/or family member in order to look for previously undetected/overlooked signs of the genetic diseases suggested by ES (reverse phenotyping). In vitro functional studies on u-RPC will be requested in a subset of patients. The number of patients with a conclusive diagnosis obtained trough these strategies will contribute to the overall diagnostic rate of the workflow (number of conclusive genetic diagnosis/number of patients enrolled in the study).
Secondary Outcomes
- Identification of molecular pathways(From enrollment (genetic testing) until the last patient last visit, estimated up to 12 months)
- Explore the applicability of gene editing in rare kidney diseases(From enrollment (genetic testing) until the last patient last visit, estimated up to 12 months)