Abstract: FR-PO675
Kidney Survival in Pediatric Patients with Pathogenic Hepatocyte Nuclear Factor 1β Variants
Session Information
- Pediatric Nephrology - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Schanstra, Joost, Inserm U1297, Toulouse, France
- Buffin-Meyer, Benedicte, Inserm U1297, Toulouse, France
- Richard, Juliette, CHU de Toulouse, Toulouse, France
- König, Jens, University Children's Hospital, Münster, Germany
- Schaefer, Franz S., Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
- Heidet, Laurence, Hôpital Necker-Enfants Malades, Paris, France
- Decramer, Stéphane, CHU de Toulouse, Toulouse, France
Group or Team Name
- HNF1B Study Group.
Background
Hepatocyte nuclear factor 1β (HNF1B) gene variants represent the most common monogenic cause of developmental kidney disease. Identification of specific genotype-phenotype associations in HNF1B disease would inform genetic counselling. The objective of this study was to determine whether the HNF1B mutation type is associated with kidney survival.
Methods
This was a retrospective observational study involving 521 patients from 14 European countries using the European ERKNet-ERN network. Mean follow-up time was 7.7 years with 6.2 visits per patient. The primary end point was progression to chronic kidney disease (CKD) stage 3 (eGFR<60 mL/min/1.73m2). Secondary endpoints were the development of extra renal abnormalities including hypomagnesemia, hyperuricemia and hyperglycemia.
Results
Progression towards CKD-stage 3 was significantly delayed in patients with the 17q12 deletion compared to patients with other pathogenic HNF1B variants (HR 0.31 (95%CI: 0.20-0.47), p<0.001). Presence of only one functional kidney due to a contralateral multicystic dysplastic kidney or agenesis was associated with accelerated CKD progression (p=0.028). Interestingly, the 17q12 deletion conferred a significant better kidney function than the other HNF1B variants already in the neonatal period. Finally, the 17q12 deletion was associated with hypomagnesemia (HR 2.49, 95%CI:1.57-4.03, p<0.001), but not with hyperuricemia or hyperglycemia.
Conclusion
Pediatric patients with the 17q12 deletion and two functional kidneys display a significantly better kidney survival than patients with other pathogenic HNF1B variants. We identified the first clinically relevant HNF1B genotype-phenotype correlation that informs genetic counselling of pediatric patients.