To investigate copeptin levels in pediatric polyuric tubulopathies such as Nephrogenic Diabetes Insipidus (NDI), Renal Fanconi syndrome and Bartter syndrome to use it as biomarker for the volume state of these patients.
ID
Source
Brief title
Condition
- Renal and urinary tract disorders congenital
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- To investigate copeptin levels in pediatric polyuric tubulopathies such as
Nephrogenic Diabetes Insipidus (NDI), Renal Fanconi syndrome and Bartter
syndrome to use it as biomarker for the volume state of these patients.
Secondary outcome
- Assess the relation between copeptin levels and other parameters of kidney
function and water and salt homeostasis. In particular:
o eGFR;
o Serum electrolytes and acid base status;
o urine and plasma osmolality;
o urinary excretion of AQP2;
o urinary levels of cAMP;
o plasma renin and aldosterone levels;
o rate of growth.
Background summary
Polyuria is defined as an excessive urinary output of more than 40-50 mL per kg
body weight per 24h, occurring as water or osmotic diuresis. Polyuria can be
caused by excessive water intake, insufficient AVP secretion or kidney
unresponsiveness to the hormone, and also as a consequence of several kidney
diseases. Some primary tubulopathies, such as nephrogenic diabetes insipidus,
Bartter syndrome, cystinosis or Dent disease, frequently associate marked
polyuria. In these entities, clinical measurement of volume status is relevant
as chronic volume depletion has been associated with a permanent
renin-angiotensin-aldosteron system activation. This, in turn may produce
kidney fibrosis and kidney function deterioration over time. However, the
assessment of volume status in clinical practice is difficult as measuring
diuresis in children can be difficult, and other surrogates of volume status,
such as plasma osmolality or arterial pressure rely on different factors other
than intravascular volume. In this context, and knowing that copeptin can be
easily measured and correlates with polyuria and volume status, the measurement
of this molecule in patients with polyuric tubulopathies could help to
differentiate patients who need a higher liquid intake to correct volume
depletion.
Study objective
To investigate copeptin levels in pediatric polyuric tubulopathies such as
Nephrogenic Diabetes Insipidus (NDI), Renal Fanconi syndrome and Bartter
syndrome to use it as biomarker for the volume state of these patients.
Study design
The present study will be an explorative multicentric cohort study, conducted
in the largest group of patients (50-100 patients) we will be able to involve
in the study, in three different time points.
Methods:
- Sample collection and processing: Blood samples will be collected into
chilled plastic tubes with disodium-EDTA and aprotinin and placed on ice
before centrifugation (at 1600×g for 15 min at 4 °C) to collect the serum and
stored at -80 °C Urine sample will be collected (added with proteasis
inhibitors), centrifuged (3000rpm 10* at 4C) and stored at -80 °C.
- AQP2 excretion and cAMP measurements: The excretion of AQP2 in urine (u-AQP2)
will be assessed by ELISA assay. The urinary excretion of AQP2 is proportional
to its expression in the kidney and in the luminal membrane of collecting duct
principal cells, representing a useful biomarker for the renal response to
vasopressin (Valenti et al. 2000). Urinary cAMP levels will be measured by
ELISA (Tsugawa et al. 1990).
- Measurement of serum copeptin: Serum copeptin levels will be assessed with
TRACE (Time Resolved Amplified Cryptate Emission) technology (KRYPTOR COMPACT
PLUS - THERMO FISHER).
- Measurement of serum renin and aldosterone: Serum renin and aldosteron levels
will be assessed with CLIA (chemiluminescent immunoassay) technology (DiaSorin
XL -PALEX).
- DDAVP test (once during any of 3 visits): Voluntary if not performed before,
as part of patient care.
Study burden and risks
Diary regarding intake and output: standard care in outpatient clinic visits
(no additional burden)
Blood: 1 tube is drawn during blood collection for regular outpatient clinic
visit (no additional burden)
Urine: 1 tube is collected durine planned urine collection for regular
outpatient clinic visit (no additional burden)
Crusces Plaza s/n
Barakaldo 48903
ES
Crusces Plaza s/n
Barakaldo 48903
ES
Listed location countries
Age
Inclusion criteria
• Child <18 years of age;
• Diagnosis of polyuric tubulopathy including Nephrogenic Diabetes Insipidus
(NDI), Renal Fanconi syndrome, Dent disease, cystinosis and Bartter syndrome,
with molecular confirmation of the disease;
• Signed Informed Consent form;
• Native kidneys;
• eGFR >= 60 ml/min/1.73 m2 (for patients older than 1 year).
Exclusion criteria
• Advanced chronic kidney disease (CKD 3-5).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL85632.042.23 |