Impaired urinary concentration ability is a sensitive predictor of renal disease progression in Joubert syndrome.
Abnormalities, Multiple
Adolescent
Adult
Biomarkers
/ urine
Cerebellum
/ abnormalities
Child
Child, Preschool
Disease Progression
Eye Abnormalities
/ complications
Female
Humans
Infant
Infant, Newborn
Kidney Diseases, Cystic
/ complications
Male
Osmolar Concentration
Renal Insufficiency, Chronic
/ diagnosis
Retina
/ abnormalities
Risk Factors
Survival Rate
Young Adult
1-deamino-8D-arginine vasopressin test
Joubert syndrome
early diagnosis
nephronophthisis
urine osmolality
Journal
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
ISSN: 1460-2385
Titre abrégé: Nephrol Dial Transplant
Pays: England
ID NLM: 8706402
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
13
03
2018
accepted:
26
09
2018
pubmed:
8
11
2018
medline:
1
12
2020
entrez:
8
11
2018
Statut:
ppublish
Résumé
Joubert syndrome (JS) is an inherited ciliopathy characterized by a complex midbrain-hindbrain malformation and multiorgan involvement. Renal disease, mainly juvenile nephronophthisis (NPH), was reported in 25-30% patients although only ∼18% had a confirmed diagnosis of chronic kidney disease (CKD). NPH often remains asymptomatic for many years, resulting in delayed diagnosis. The aim of the study was to identify a biomarker able to quantify the risk of progressive CKD in young children with JS. Renal features were investigated in 93 Italian patients, including biochemical tests, ultrasound and 1-deamino-8D-arginine vasopressin test in children with reduced basal urine osmolality. A subset of patients was followed-up over time. At last examination, 27 of 93 subjects (29%) presented with CKD, ranging from isolated urinary concentration defect (UCD) to end-stage renal disease. Both normal and pathological urine osmolality levels remained stable over time, even when obtained at very early ages. Follow-up data showed that the probability of developing CKD can be modelled as a function of the urine osmolality value, exceeding 75% for levels <600 mOsm/kg H2O, and significantly increased in patients with an early diagnosis of isolated UCD. We conclude that the frequency of CKD in JS increases with age and is higher than previously reported. Urine osmolality represents an early sensitive quantitative biomarker of the risk of CKD progression.
Sections du résumé
BACKGROUND
Joubert syndrome (JS) is an inherited ciliopathy characterized by a complex midbrain-hindbrain malformation and multiorgan involvement. Renal disease, mainly juvenile nephronophthisis (NPH), was reported in 25-30% patients although only ∼18% had a confirmed diagnosis of chronic kidney disease (CKD). NPH often remains asymptomatic for many years, resulting in delayed diagnosis. The aim of the study was to identify a biomarker able to quantify the risk of progressive CKD in young children with JS.
METHODS
Renal features were investigated in 93 Italian patients, including biochemical tests, ultrasound and 1-deamino-8D-arginine vasopressin test in children with reduced basal urine osmolality. A subset of patients was followed-up over time.
RESULTS
At last examination, 27 of 93 subjects (29%) presented with CKD, ranging from isolated urinary concentration defect (UCD) to end-stage renal disease. Both normal and pathological urine osmolality levels remained stable over time, even when obtained at very early ages. Follow-up data showed that the probability of developing CKD can be modelled as a function of the urine osmolality value, exceeding 75% for levels <600 mOsm/kg H2O, and significantly increased in patients with an early diagnosis of isolated UCD.
CONCLUSIONS
We conclude that the frequency of CKD in JS increases with age and is higher than previously reported. Urine osmolality represents an early sensitive quantitative biomarker of the risk of CKD progression.
Identifiants
pubmed: 30403813
pii: 5162973
doi: 10.1093/ndt/gfy333
pmc: PMC7417010
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1195-1202Subventions
Organisme : European Research Council
ID : 260888
Pays : International
Informations de copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA.
Références
Am J Hum Genet. 2017 Oct 5;101(4):552-563
pubmed: 28965847
Am J Med Genet A. 2017 Mar;173(3):661-666
pubmed: 28052552
PLoS Biol. 2016 Mar 16;14(3):e1002416
pubmed: 26982032
Am J Med Genet A. 2017 May;173(5):1237-1242
pubmed: 28371402
Pediatrics. 1976 Aug;58(2):259-63
pubmed: 951142
Am J Hum Genet. 2007 Jul;81(1):104-13
pubmed: 17564967
J Med Genet. 2015 Aug;52(8):514-22
pubmed: 26092869
Kidney Int Suppl (2011). 2017 Dec;7(3):e1
pubmed: 30681074
Hum Mutat. 2014 Oct;35(10):1153-62
pubmed: 25044745
Lancet Neurol. 2013 Sep;12(9):894-905
pubmed: 23870701
Hum Genet. 2017 Apr;136(4):399-408
pubmed: 28220259
J Med Genet. 2016 Sep;53(9):608-15
pubmed: 27208211
J Am Soc Nephrol. 2009 May;20(5):1123-31
pubmed: 19389850
J Pathol. 2017 Jan;241(2):294-309
pubmed: 27859258
Orphanet J Rare Dis. 2010 Jul 08;5:20
pubmed: 20615230
Genet Med. 2017 Aug;19(8):875-882
pubmed: 28125082
Clin J Am Soc Nephrol. 2017 Dec 7;12(12):1962-1973
pubmed: 29146704
Arch Dis Child. 1974 Aug;49(8):654-9
pubmed: 4425527
J Am Soc Nephrol. 2009 Mar;20(3):629-37
pubmed: 19158356