Validation, implementation, and cost-analysis of a strategy for personalized diagnosis of rare kidney diseases

Chronic kidney disease (CKD) affects 10% of the world population with high morbility and mortality. Genetic kidney diseases are increasingly recognized across all age groups and represent over 20% of all the causes of CKD. Whole-exome sequencing (WES) increases the diagnostic rate of genetic kidney disorders but accessibility, interpretation of results, and costs limit its use in daily practice. We addressed this problem at four levels: 1. applying clinical criteria for a standardized selection of patients that should undergo genetic testing; 2. centralizing genetic diagnosis by whole-exome sequencing, reverse-phenotyping, multidisciplinary board analysis; 3. applying cutting edge technologies to support diagnosis of genetic and non-genetic rare kidney diseases; 4. optimizing the use of resources and increasing cost-effectiveness for the health provider.
Preliminary results derived from the application of this personalized diagnostic algorithm on a local study led to a global diagnostic yield of 70%, suggesting that this strategy has the potential to substantially improve the diagnostic approach to patients with rare kidney disorders. In this project we propose to perform a validation and implementation of this workflow by: 1. Extending its assessment in a multicentric study involving nephrology units that are referral centers for rare kidney diseases at national level.
2.supporting diagnosis of genetic and non-genetic patients by cutting edge technologies, i.e. STED super resolution microscopy of kidney biopsy and individual disease modelling by 3D organ-on-a-chip model system prepared using patient urine-derived renal progenitor cultures.
3. Assessing the cost-effectiveness as well as clinical, ethical, and legal consequences of the application of this workflow showing the feasibility in a real-world setting and its impact in reducing costs for the health system.
The results of this project have the potential to significantly innovate diagnosis and clinical management of patients affected by rare kidney diseases with potential benefits for patients and the health system.
This project deals exclusively with the primary MDC "Nefrologia and Urologia", since is fully focused only on kidney diseases, dealing with potentially over 700 rare diseases that only have the kidney in common. This makes impossible to indicate a secondary MDC.