Primary Objective: • To compare urinary concentrating capacity in ADPKD patients with healthy subjects and patient with IgA- or membranous glumerulopathy.Secondary Objectives:• To compare urinary concentrating capacity in ADPKD patients with an eGFR…
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Plasma AVP and copeptin levels in relation to maximum plasma osmolality and
urinary osmolality.
Secondary outcome
Not applicable
Background summary
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most prevalent
hereditary renal disease, characterized by massive cyst formation in the
kidneys and leading to end-stage renal disease. It is clinically acknowledged
that ADPKD patients cannot concentrate their urine as well as healthy subjects.
The mechanism behind the impaired urinary concentrating capacity in ADPKD is,
however, unknown. One of the theories is that insensitivity for vasopressin and
compensatory higher levels of vasopressin play a role. Importantly, vasopressin
has recently been hypothesized to involved in the causal pathway leading to
cyst formation, cyst growth and renal function deterioration. In line with this
hypothesis it has recently been described that vasopressin (AVP), measured as
its precursor copeptin, is associated with various markers of ADPKD severity,
such as low renal function (GFR) and high total renal volume.
A water deprivation test can be helpful to learn more about the underlying
mechanism of the impaired urinary concentrating capacity in ADPKD. With this
test it will be possible to investigate urinary concentrating capacity,
AVP/copeptin levels in relation to plasma osmolality in ADPKD patients and to
compare these to values obtained in healthy subjects.
Our hypotheses for the present study are that ADPKD patients cannot concentrate
their urine as well as healthy controls because of insensitivity of the kidney
for vasopressin (showing as a high level of AVP/copeptin for plasma osmolality,
but less concentrated urine) and that ADPKD patients with a lower eGFR have a
less urinary concentrating capacity (and higher AVP/copeptin levels for plasma
osmolarity) when compared to ADPKD patients with a higher eGFR. We also think
ADPKD patients cannot concentrate their urine as well as patients with another
chronic kidney because of insensitivity of the kidney for vasopressin. To study
this we will include a patient controle group consisting of 15 IgA- and
membranous nephropathy patients with the same eGFR.
Study objective
Primary Objective:
• To compare urinary concentrating capacity in ADPKD patients with healthy
subjects and patient with IgA- or membranous glumerulopathy.
Secondary Objectives:
• To compare urinary concentrating capacity in ADPKD patients with an eGFR >60
ml/min/1.73m2 and an eGFR <60 ml/min/1.73m2.
• To compare AVP/copeptin levels in ADPKD patients with healthy subjects in
relation to plasma osmolality in a normal hydration status and at maximal
urinary concentration.
• To compare AVP/copeptin levels in relation to serum osmolality in ADPKD
patients with an eGFR >60 ml/min/1.73m2 and an eGFR <60 ml/min/1.73m2 in a
normal hydration status and at maximal urinary concentration.
• To rule out a central (hypofyse) component of decreased urinary concentrating
capacity by using injected dDAVP intramuscular
• To compare AVP/copeptin levels in ADPKD patients with healthy subject in
relation to (maximal) urinary concentration.
• To compare AVP/copeptin levels in relation to (maximal) urine concentration
in ADPKD patients with an eGFR >60 ml/min/1.73m2 and an eGFR <60 ml/min/1.73m2
• To compare urinary concentrating capacity in ADPKD patients with IgA- and
membranous nephropathy patients with similar (impaired) renal function
• To compare AVP/copeptin levels in ADPKD patients with IgA- and membranous
nephropathy patients with similar (impaired) renal function, in relation to
serum osmolality in a normal hydration status and at maximal urinary
concentration.
Study design
This is a one-day "intervention" study, cross-sectional in design, comparing
results in ADPKD patients to results in healthy controls.
Intervention
The patients and healthy controls will undergo a standard water deprivation
test, based on van der Berg, Robertson and Farquhar. In summary, the patient
starts thirsting from 6 p.m. the day before the test. Before starting a urine
sample and serum sample will be collected and a simple meal will be eaten. This
day they are not allowed to drink any coffee and tea or eat chocolate. The
actual test starts at 8 a.m. the next morning, after weighting the patient
after emptying the bladder. An infusion needle will be inserted. The subjects
are not allowed to eat or drink anything. Then, every hour urine and every 2
hours blood samples will be collected. Every two hours, the patient will be
weighed .
During this test, urine and plasma samples are collected and osmolality,
sodium, potassium, glucose and urine volume will be measured. When the urine
osmolality becomes constant with less than a 30 mOsml/kg increase in osmolality
between two collection periods, dDAVP will be injected intramuscular, so
pituitary vasopressin deficiency can be excluded. After this, the subject will
stay another two hours for measuring plasma and urine samples. Of note, if
participants have not reached their plateau in urinary osmolarity at 14.30 p.m.
after a maximum of almost 21 hours of thirsting, dDAVP will also be injected.
Study burden and risks
There are no (in)direct benefits for the participating subjects. The risks of
this test are subjects can get hyperosmolar (measured as an increase in plasma
sodium concentration) which can result in cerebral effects and/or dehydration.
Administration of dDAVP, in the dosage listed in the protocol, can incidentally
(<1%) lead to headache, nauseau or stomach ache. Also, several blood
withdrawals can lead to haematoma.
The water deprivation test, as described in this protocol, is a standard water
deprivation test as executed by the department of Endocrinology at the UMCG in
patients with suspected diabetes insipidus. These water deprivation tests are
normally executed at the daycentre of the department of Internal Medicine,
where no medical supervision is present. There is a theoretical chance of
developing hypernatremia with cerebral effects and/or dehydration. The
probability these complications occur is minimal. Plasma sodium concentration
will be measured repeatedly and the water deprivation test will also be
terminated when it exceeds 150 mmol/L. Also body weight will be measured and
the test will be terminated if body weight decreases more than 3%. The
information leaflet of dDAVP mentions adverse effects in the dosage used in
this protocol are incidental and mild. This is conform the clinical experience
of the department of Endocrinology. To make blood withdrawals as comfortable as
possible an infusion needle will be inserted in an antecubital vein. With the
help of this infusion needle blood can be collected while only one puncture is
needed.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
The diagnosis of ADPKD will be assessed as routinely by the Ravine criteria, and ADPKD patients will be selected to be between 18 and 65 years of age, and stratified for eGFR, with 15 ADPKD patients having an eGFR <60 ml/min/1.73 m2 and 15 ADPKD patients having an eGFR >60 ml/min/1.73 m2.;The diagnosis IgA- or membranous nephropathy will be based upon clinical history and laboratory values, according to clinical practice. IgA- and membranous nephropathy patients will be selected to be between 18 and 65 years . IgA- and membranous nephropathy patients need to be in a stable disease phase of their disease, as defined by proteinuria <1 g/d and eGFR loss less than 5 ml/min/1.73m2 in the previous year, without use of immunosuppressive medication.;Healthy volunteers will be considered as healthy, in case of an eGFR >60 ml/min/1.73 m2, albuminuria less than 30 mg/d, absence of plasma electrolyte concentration abnormalities.
Healthy volunteers will be selected to be between 18 and 65 years of age. ;The day before the water deprivation test urine will be collected and a vena punction will we done. We will use the vena punction to determine the eGFR and plasma electrolyte concentration abnormalities. A urine dipstick showing negative or trace is used to rule out albuminuria. We will have the results before the waterdeprivation test starts the next day.
Exclusion criteria
ADPKD subjects, IgA- and membraneuze nephropathie subjects and healthy volunteers are excluded in case they use medication or have comorbidities that may affect urinary concentration capacity, medication being the use of diuretics or vasopressin receptor antagonists, and comorbity being diabetes mellitus (DM), diabetes insipidus or kidney disease other than ADPKD.;Other exclusion criteria are:
- those diseases / factors that are known to influence vasopressin concentration: smoking, alcohol use of 4 or more consumptions per day, hypovolemia of any cause, deficiency of adrenal or thyroid hormone, pregnancy, menstruation at time of the water deprivation test or using postmenopausal hormone therapy (because estrogen influences AVP release).
- active cardiovascular disease (angina pectoris).
- urinary tract infection
- incapabability of understanding the informed consent form, signing the consent or unability to comply with all requirements of the trial.;To gain more information about their eGFR, use of medication, comorbidities that may affect urinary concentration capacity and other exclusion criteria (active cardiovascular disease), ADPKD patients and IgA- and nephropathy patients will be asked for approval of insight in their medical records. This is not necessary for healthy volunteers, we will collect information about inclusion and exclusion criteria by anamnesis. We will not test any of the exclusion criteria otherwise besides an anamnesis.
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 | NL33996.042.10 |