ESPN 54th Annual Meeting

ESPN 2022


 
A clinical workflow for selection of patients and cost-effective diagnosis of genetic kidney diseases
FRANCESCA BECHERUCCI 1 LUIGI CIRILLO 2 SAMUELA LANDINI 1 VIVIANA PALAZZO 1 VALENTINA RAGLIANTI 2 GIANMARCO LUGLI 2 LUCIA TIBERI 2 AUGUSTO VAGLIO 2 HANS JOACHIM ANDERS 3 BENEDETTA MAZZINGHI 1 PAOLA ROMAGNANI 2

1- MEYER CHILDRENS HOSPITAL
2- UNIVERSITY OF FLORENCE
3- LUDWIG MAXIMILIANS UNIVERSITY MUNICH
 
Introduction:

Genetic kidney diseases (GKD) are increasingly recognized across all age groups. However, accessibility, interpretation of results, and costs limit the widespread of genomics use in daily practice. In this work, we explored the feasibility and diagnostic performance of a service delivery model for diagnosis of GKD.

Material and methods:

We established specific clinical criteria for selection of patients that should undergo genetic testing in the suspicion of a GKD by a network of nephrology centers. Patients selected were referred to a tertiary center for genetic diagnosis by whole-exome sequencing, reverse-phenotyping, and multidisciplinary board analysis.
This multi-step workflow was applied to pediatric and adult patients with clinical diagnosis belonging to different categories (Podocytopathies, Collagenopathies, Tubulopathies, Unknown familial nephropathies, Ciliopathies, Congenital anomalies of the kidney and urinary tract, Syndromic chronic kidney disease, Metabolic kidney disorders). We recorded clinical data information of patients included. We also performed a cost-analysis of the diagnostic workflow.

Results:

We included 402 patients. We obtained a global diagnostic yield of 69.2% (278/402), with category-specific diagnostic rates ranging from 38.5% to 87%. By reverse phenotyping, we reclassified diagnoses in 74/278 (26.6%) patients, thus increasing diagnostic accuracy. Diagnostic yield was independent of the age at onset of kidney disease. Obtaining a conclusive genetic diagnosis significantly affected clinical management of patients and led to cascade diagnosis in family members with unexplained or overlooked clinical manifestations. Finally, cost-analysis showed that our workflow is cost-efficient allowing to potentially save a mean of 1360 euros per patient.

Conclusions:

Ordering genetic testing, interpreting results, counseling patients and their families and tailoring clinical management (i.e., personalized nephrology) is feasible and saves costs in a real-world setting.