ESPN 53rd Annual Meeting

ESPN 2021


 
Prediction of renal prognosis in nephronophthisis
JENS KÖNIG 1 REBEKA KARSAY 1 JOACHIM GERß 11 KARL PETER SCHLINGMANN 1 MAREIKE DAHMER-HEATH 1 ANNA-KATHARINA TELGMANN 1 SABINE KOLLMANN 1 GEMA ARICETA 2 VALENTINE GILLION 3 DETLEF BOCKENHAUER 4 AURELIA BERTHOLET-THOMAS 5 ANTONIO MASTRANGELO 6 OLIVIA BOYER 7 MARC LILIEN 8 STEPHANE DECRAMER 9 JOOST-PETER SCHANSTRA 10 PETRA PENNEKAMP 1 MARTIN KONRAD 1

1- UNIVERSITY CHILDRENS HOSPITAL, DEPARTMENT OF GENERAL PEDIATRICS, UNIVERSITäTSKLINIKUM MÜNSTER, MÜNSTER, GERMANY
2- SERVICIO DE NEFROLOGíA PEDIáTRICA, HOSPITAL VALL DHEBRON, UNIVERSITAT AUTóNOMA DE BARCELONA, BARCELONA, SPAIN
3- DIVISION OF NEPHROLOGY, SAINT-LUC ACADEMIC HOSPITAL, UNIVERSITé CATHOLIQUE LOUVAIN, BRUSSELS, BELGIUM
4- DEPARTMENT RENAL MEDICINE, UNIVERSITY COLLEGE LONDON, LONDON, UK
5- CENTRE DE RéFéRENCE DES MALADIES RéNALES RARES-NéPHROGONES-HôPITAL FEMME MèRE ENFANT, HOSPICES CIVILS DE LYON-FILIèRE ORKID, BRON, FRANCE
6- FONDAZIONE IRCCS CA GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY
7- SERVICE DE NéPHROLOGIE PéDIATRIQUE, CENTRE DE RéFéRENCE DES MALADIES RéNALES HéRéDITAIRES DE LENFANT ET DE LADULTE (MARHEA), INSTITUT IMAGINE, HôPITAL NECKER-ENFANTS MALADES, UNIVERSITé DE PARIS, PARIS, FRANCE
8- DEPARTMENT OF PAEDIATRIC NEPHROLOGY, WILHELMINA CHILDRENS HOSPITAL, UNIVERSITY MEDICAL CENTER UTRECHT AND UTRECHT UNIVERSITY, UTRECHT, THE NETHERLANDS
9- INSTITUT NATIONAL DE LA SANTé ET DE LA RECHERCHE MéDICALE (INSERM), U1048, INSTITUT OF CARDIOVASCULAR AND METABOLIC DISEASE, TOULOUSE, FRANCE; UNIVERSITé TOULOUSE III PAUL-SABATIER, TOULOUSE, FRANCE; SERVICE DE NéPHROLOGIE PéDIATRIQUE, HôPITAL DES ENFANTS, CHU TOULOUSE, TOULOUSE, FRANCE; CENTRE DE RéFéRENCE DES MALADIES RéNALES RARES DU SUD-OUEST (SORARE), TOULOUSE, FRANCE
10- UNIVERSITé TOULOUSE III PAUL-SABATIER, 31330, TOULOUSE, FRANCE
11- INSTITUTE OF BIOSTATISTICS AND CLINICAL RESEARCH, UNIVERSITY OF MÜNSTER, MÜNSTER, GERMANY
 
Introduction:

Nephronophthisis comprises rare genetic defects accounting for 10% of end-stage kidney disease (ESKD) in children. Despite the improved molecular understanding, prediction of individual renal prognoses still poses a major challenge. To overcome this burden, we assessed differences in genotype-specific kidney survival, the impact of mutational severity and the influence of other clinical characteristics on the decline of kidney function.

Material and methods:

Information was obtained from 3 independent data sources: the Network of Early Onset Cystic Kidney Diseases (NEOCYST) clinical registry (n=105), an online survey sent out to the members of the European Reference Network for Rare Kidney Diseases (n=60) and a complementary literature search (n=227).

Results:

392 genetically characterized individuals were available for analysis: 117 NPHP1, 85 NPHP3, 87 NPHP4 and 103 NPHP11. Kidney survival curves differed between the four cohorts with a highly variable outcome for onset of age when 50% of participants reached ESKD: NPHP3 4.0 yrs, NPHP1 13.5 yrs, NPHP4 16.0 yrs and NPHP11 19.0 yrs. Above that, for NPHP3 and NPHP4 kidney survival was significantly associated with the severity of the underlying genetic defect (p<0.01). Multivariate analysis based on the phenotypic details available for the NPHP1 cohort additionally revealed arterial hypertension (HR 3.298) and growth retardation (HR 2.178) as two independent factors associated with an earlier onset of ESKD. Finally, the use of ACE inhibitors initiated for the treatment of arterial hypertension +/- proteinuria was significantly associated with a more rapid annual GFR decline (13.0 vs. 6.2 ml/min/1,73m2) in patients with underlying NPHP1 defect.

Conclusions:

The present study represents the largest of its kind, addressing the kidney survival of the most relevant genetic causes of nephronophthisis. The presented data will enable clinicians to further classify and estimate the renal prognosis of their patients and thereby allow for personalized counselling.