ESPN 54th Annual Meeting

ESPN 2022


 
Current Clinical Practice of Genetic Screening in Patients with Hereditary Diseases: Findings from the European Rare Kidney Disease Registry (ERKReg)
GIULIA BASSANESE 1 TANJA WLODKOWSKI 1 AUDE SERVAIS 2 DARIO ROCCATELLO 3 LAURENCE HEIDET 4 FRANCESCO EMMA 5 GEMA ARICETA 6 STéPHANE DECRAMER 7 ELENA LEVTCHENKO 8 AUGUSTINA JANKAUSKIENE 9 GIOVANNI MONTINI 10 JUN OH 12 JAAP GROOTHOFF 11 FRANZ SCHAEFER 1

1- 1. DIVISION OF PEDIATRIC NEPHROLOGY, CENTER FOR PEDIATRICS AND ADOLESCENT MEDICINE, UNIVERSITY OF HEIDELBERG, HEIDELBERG, GERMANY
2- 2. NEPHROLOGY AND TRANSPLANTATION DEPARTMENT, CENTRE DE RéFéRENCE DES MALADIES RéNALES HéRéDITAIRES DE L’ENFANT ET DE L’ADULTE, NECKER UNIVERSITY HOSPITAL, APHP, UNIVERSITé DE PARIS, PARIS, FRANCE
3- 3. NEPHROLOGY AND DIALYSIS UNIT, SAN GIOVANNI HUB HOSPITAL AND DEPARTMENT OF CLINICAL AND BIOLOGICAL SCIENCES, UNIVERSITY OF TURIN, TURIN, ITALY
4- 4. APHP, PEDIATRIC NEPHROLOGY UNIT, CENTRE DE RéFéRENCE DES MALADIES RéNALES HéRéDITAIRES DE L’ENFANT ET DE L’ADULTE (MARHEA), HôPITAL UNIVERSITAIRE NECKER-ENFANTS MALADES, 75015, PARIS, FRANCE
5- 5.DIVISION OF NEPHROLOGY, BAMBINO GESù CHILDREN’S HOSPITAL IRCCS, ROME, ITALY
6- 6.DEPARTMENT OF PAEDIATRIC NEPHROLOGY, HOSPITAL UNIVERSITARIO VALL D’HEBRON, BARCELONA, SPAIN
7- 7. PEDIATRIC NEPHROLOGY, INTERNAL MEDICINE AND RHEUMATOLOGY, SOUTHWEST RENAL RARES DISEASES CENTRE (SORARE), UNIVERSITY CHILDREN’S HOSPITAL, TOULOUSE
8- 8.DEPARTMENT OF PEDIATRIC NEPHROLOGY AND DEVELOPMENT AND REGENERATION, UNIVERSITY HOSPITALS LEUVEN, UNIVERSITY OF LEUVEN, LEUVEN, BELGIUM
9- 9. VILNIUS UNIVERSITY HOSPITAL SANTAROS KLINIKOS, PEDIATRIC CENTER, VILNIUS UNIVERSITY, VILNIUS, LITHUANIA
10- 10.PEDIATRIC NEPHROLOGY, DIALYSIS AND TRANSPLANT UNIT, FONDAZIONE CA’ GRANDA IRCCS, POLICLINICO DI MILANO, MILAN, ITALY
11- 11.DEPARTMENT OF PEDIATRIC NEPHROLOGY, AMSTERDAM UNIVERSITY MEDICAL CENTER, AMSTERDAM, THE NETHERLANDS.
12- Pediatric Nephrology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
 
Introduction:

 Genetic screening is rapidly moving from a research tool to the first-line diagnostic procedure for hereditary kidney diseases. We examined the current state of genetic screening for hereditary nephropathies in Europe.

 

Material and methods:

Since 2019, the European Rare Kidney Disease Registry (ERKReg) has monitored diagnostic procedures in >13.000 patients at 75 centers in 24 European countries. Here we evaluated the use of genetic screening in 4.242 registry patients diagnosed with a rare kidney disease from 01/16-12/21.

Results:

Genetic screening was performed in 1.259 patients, including 53% of all patients with tubulopathies (TP) and metabolic nephropathies (MNP), 39% of ciliopathy patients, 38% of patients presenting with thrombotic microangiopathies (TMA), 27% of glomerulopathy and 11% of CAKUT patients. Genetic screening for hereditary diseases was ordered twice as common in pediatric as in adult patients (36% v. 18%). Among the patients screened, a genetic diagnosis was established in 96% of MNP, 92% of ciliopathies, 91% of TP, 68% of TMA and 56% of CAKUT cases.  

The screening turnaround time shortened over time to a current median of 3.4 months. Notable differences were noticed between countries, with a range of 1.3 months in Germany to 10.5 months in Italy. Saenger sequencing of individual genes was used in 22%, NGS gene panels in 63% and whole exome sequencing in 15% of patients. Median turnaround time was 2.5 months for Saenger, 3.3 months for NGS panel screening, and 5.8 months for whole exome sequencing. In those patients in whom a genetic diagnosis was established, median time to genetic diagnosis was 10 months from disease onset, and 8.5 months from referral to the specialist center.

Conclusions:

 Genetic screening yields remarkably high diagnostic confirmation rates.  While decreasing, laboratory turnaround times still require improvement to maximize the clinical usefulness of genetic screening.