Heterogeneity is a common ground in familial hypomagnesemia with hypercalciuria and nephrocalcinosis caused by CLDN19 gene mutations.
CLDN19
FHHNC
Hypomagnesemia
Renal failure (RF)
Journal
Journal of nephrology
ISSN: 1724-6059
Titre abrégé: J Nephrol
Pays: Italy
ID NLM: 9012268
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
received:
19
05
2020
accepted:
19
04
2021
pubmed:
1
5
2021
medline:
29
1
2022
entrez:
30
4
2021
Statut:
ppublish
Résumé
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare tubulopathy caused by mutations in the CLDN16 or CLDN19 genes. Patients usually develop hypomagnesemia, hypercalciuria, nephrocalcinosis and renal failure early in life. Patients with CLDN19 mutations may also have ocular abnormalities. Despite clinical variability, factors associated with kidney function impairment, especially in patients with CLDN19 mutations, have not been addressed. Retrospective multicenter study of 30 genetically confirmed FHHNC Spanish patients. We analyzed kidney function impairment considering as outcomes chronic kidney disease (CKD) stage 3 and annual estimated glomerular filtration rate (eGFR) decline, to identify factors associated with the different phenotypes. Of thirty patients, 27 had mutations in the CLDN19 gene (20 homozygous for the p.G20D mutation) and 3 in the CLDN16. Age at diagnosis was 1.71 (0.67-6.04) years and follow-up time was 8.34 ± 4.30 years. No differences in CKD stage 3-free survival based on CLDN19 mutation (p.G20D homozygous vs. other mutations) or gender were found, although females seemed to progress faster than males. Patients with more pronounced eGFR decline had higher PTH levels at diagnosis than those with stable kidney function, despite similar initial eGFR. Approximately 60% of CLDN19 patients presented ocular abnormalities. Furthermore, we confirmed high phenotypic intrafamilial variability. In a contemporary cohort of FHHNC patients with CLDN19 mutations, females seemed to progress to CKD-stage 3 faster than males. Increased PTH levels at baseline may indicate a more severe renal course. There was high phenotype variability among patients with CLDN19 mutations and kidney function impairment differed even between siblings.
Sections du résumé
BACKGROUND
BACKGROUND
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare tubulopathy caused by mutations in the CLDN16 or CLDN19 genes. Patients usually develop hypomagnesemia, hypercalciuria, nephrocalcinosis and renal failure early in life. Patients with CLDN19 mutations may also have ocular abnormalities. Despite clinical variability, factors associated with kidney function impairment, especially in patients with CLDN19 mutations, have not been addressed.
METHODS
METHODS
Retrospective multicenter study of 30 genetically confirmed FHHNC Spanish patients. We analyzed kidney function impairment considering as outcomes chronic kidney disease (CKD) stage 3 and annual estimated glomerular filtration rate (eGFR) decline, to identify factors associated with the different phenotypes.
RESULTS
RESULTS
Of thirty patients, 27 had mutations in the CLDN19 gene (20 homozygous for the p.G20D mutation) and 3 in the CLDN16. Age at diagnosis was 1.71 (0.67-6.04) years and follow-up time was 8.34 ± 4.30 years. No differences in CKD stage 3-free survival based on CLDN19 mutation (p.G20D homozygous vs. other mutations) or gender were found, although females seemed to progress faster than males. Patients with more pronounced eGFR decline had higher PTH levels at diagnosis than those with stable kidney function, despite similar initial eGFR. Approximately 60% of CLDN19 patients presented ocular abnormalities. Furthermore, we confirmed high phenotypic intrafamilial variability.
CONCLUSIONS
CONCLUSIONS
In a contemporary cohort of FHHNC patients with CLDN19 mutations, females seemed to progress to CKD-stage 3 faster than males. Increased PTH levels at baseline may indicate a more severe renal course. There was high phenotype variability among patients with CLDN19 mutations and kidney function impairment differed even between siblings.
Identifiants
pubmed: 33929692
doi: 10.1007/s40620-021-01054-6
pii: 10.1007/s40620-021-01054-6
doi:
Substances chimiques
CLDN19 protein, human
0
Claudins
0
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
2053-2062Subventions
Organisme : Instituto de Salud Carlos III
ID : PI14/01107
Organisme : Instituto de Salud Carlos III
ID : PI18/01107
Informations de copyright
© 2021. Italian Society of Nephrology.
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