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
only18% 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.
- 1-deamino-8D-arginine vasopressin test
- early diagnosis
- Joubert syndrome
- urine osmolality