ESPN 51th Annual Meeting

ESPN 2018


 
RENAL KIDNEY DISEASE PROGRESION IN A CONTEMPORARY GROUP OF FAMILIAL HYPOMAGNESEMIA WITH HYPERCALCIURIA AND NEPHROCALCINOSIS PATIENTS
MòNICA VALL 1 SARA CHOCRóN 2 FéLIX CLAVERIE-MARTIN 3 ANNA MESEGUER 1 GEMA ARICETA 2

1- FISIOPATOLOGíA RENAL – CIBBIM NANOMEDICINA, VALL D’HEBRON INSTITUT DE RECERCA (VHIR), BARCELONA, SPAIN
2- SERVICIO DE NEFROLOGíA PEDIáTRICA, HOSPITAL UNIVERSITARI VALL D’HEBRON, UNIVERSITAT AUTONOMA DE BARCELONA, BARCELONA, SPAIN
3- UNIDAD DE INVESTIGACIóN, HOSPITAL NUESTRA SEñORA DE CANDELARIA, SANTA CRUZ DE TENERIFE, SPAIN
 
Introduction:

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal-recessive disorder caused by CLDN16 or CLDN19 gene mutations. Patients develop hypomagnesemia, hypercalciuria, nephrocalcinosis and end-stage renal disease (ESRD) early in life. Most CLDN19 patients present ocular abnormalities (i.e. colobamata, nystagmus and severe myopia). However, phenotypic variability exists even in homozygous p.G20D (c.59G>A) CLDN19 mutation patients and, interestingly, between siblings. Possibly, the better knowledge of FHHNC has contributed to delay ESRD progression. Here, we describe clinical-genetic characteristics and the evolution of a FHHNC cohort.

Material and methods:

 

Clinical-genetic data was provided by clinicians (RenalTube) after patient’s informed consent acceptation.

 

Results:

 

We describe 30 FHHNC genetically diagnosed patients of 15.51±9.99 years-old, belonging to 22 unrelated families, including 8 pairs of siblings: 3 patients with mutation in CLDN16 while 27 (90%) in CLDN19, of which, 63% (n=19) are p.G20D homozygous. Renal function at diagnosis (3.72±4.69 years) was 70.30±17.83mL/min/1,73m2.

At renal level, patients were classified in severe renal phenotype (ESRD<4 years-old, n=5, 17%), moderate (n=19, 63%); and mild (minor CKD>18 years-old or ESRD>25, n=6, 30%). Renal survival at 4 years-old is 83% and the median age is 25.42 years. After 10.2 years of clinical follow-up, the actual situation is: 10 (33%) with ESRD (9 transplanted and 1 in dialysis) and 20 (66%) with native kidneys. Females represent 80% of ESRD group, whilst only 40% of non-ESRD group. Regarding the ocular phenotype, 16 (53%) patients exhibit the prototypic; 6 (20%) undetermined; and 8 (27%) have no abnormalities. In 4/8 pairs of siblings there are differences in renal and ocular phenotype, although without a direct relation between renal progression and ocular severity.

 

Conclusions:

 

Despite the severity of FHHNC, an early clinical-genetic diagnosis could delay progression to ESRD, although there is evidence of other factors involved, even in genotypically identical patients and siblings. Female gender is associated with more severe kidney disease.