To predict the progression of CKD with diuretic testing.
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Composite outcome of CKD progression, defined as a 30% decrease in estimated
glomerular filtration rate (eGFR) or the start of kidney replacement therapy
with dialysis or transplantation, during a 3-year follow-up period.
Secondary outcome
To investigate tubular physiology in chronic kidney disease
• Diuretic clearance in CKD
• Fractional electrolyte excretion compared with tubular diuretic concentrations
• Uromodulin and epidermal growth factor (EGF) concentrations in urine before
and after stimulation as these are both secreted by the distal tubule
• Feasibility of the tubular function test in clinical practice
• Fraction excretion of ESSs in comparison to the diuretic clearance as a
marker for proximal tubular dysfunction
• eGFR slope
• Incident cardiovascular disease
• Mortality
Background summary
Chronic kidney disease (CKD) is a common and often progressive condition. CKD
is currently only assessed by glomerular function and not tubular function. We
hypothesize that measuring tubular function can predict the progression of CKD.
To investigate this, we will test tubular function with diuretics in patients
with CKD and follow them over a 3-year period to monitor CKD progression.
Study objective
To predict the progression of CKD with diuretic testing.
Study design
Single-centre, prospective diagnostic trial.
Intervention
After a 4-week washout period of interfering drugs, participants will undergo
diuretic testing involving the concurrent oral administration of bumetanide (2
mg) and hydrochlorothiazide (HCTZ, 50 mg). Blood and urine will be collected to
assess kidney tubular function. 24-hour urine will be collected on the day
before the test. On the test day, a standardized breakfast and lunch will be
served, and subjects will drink a standardized amount of water. We will recruit
81 patients with CKD, including 76 patients who will undergo the test and 5
randomly chosen patients who will not receive the diuretics and will serve as
time controls (to correct for diurnal variations in urine and blood
composition, age and sex matched). Additionally, 5 healthy controls will
undergo the test to compare the diuretic response in patients with CKD to
healthy participants (age and sex matched).
Study burden and risks
We have minimized the trial burden by organizing the test as a single-day
protocol. Bumetanide and HCTZ are frequently used diuretics with a good overall
safety profile. The safe use of these diuretics in a 1-day diuretic testing
protocol has been reported previously. Although chronic use of these diuretics
may lead to fluid and electrolyte imbalance, the risk of a single
administration for diagnostic purposes is expected to be minimal. In addition,
all participants are monitored for 6 hours after administration of the
diuretics, including blood pressure measurement and blood gas analysis. All
procedures concerning sample collection are part of routine clinical care and
are generally safe. The burden of blood sample collection will be minimized by
cannulating a single vein once to collect blood samples at the six necessary
time points. Patients will be reimbursed for their participation.
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Listed location countries
Age
Inclusion criteria
Adult (>= 18 years)
CKD stage G3 (creatinine-based eGFR 30-59 mL/min/1.73m2) during the last
outpatient visit
Exclusion criteria
Known intolerance or allergy to the diuretics
Current systemic chemotherapy for malignancy
Kidney transplant recipient
Use of calcineurin-inhibitors
Life expectancy < 12 months
Current immunosuppressive treatment for glomerulonephritis
Incapacitated subjects or subjects who are deemed unfit to adequately adhere to
instructions from the research team
Hypokalemia or hyperkalemia (K+ < 3.0mmol/L or K+ > 5.5 mmol/L) at inclusion
visit
Hypo- or hypernatremia (Na+ < 130 mmol/L or Na+ > 150mmol/L) at inclusion visit
Inherited tubulopathy as the cause of CKD
Autosomal dominant polycystic or tubulointerstitial kidney disease causing CKD
Clinically relevant heart failure (New York Heart Association class III or IV)
Therapy-resistant hypertension, defined as systolic blood pressure > 180mmHg at
the inclusion visit
Current treatment with inhibitors of OATs: probenecid, pravastatin, cimetidine,
cephalosporins, acetazolamide
Active hepatitis during the last outpatient visit
Liver cirrhosis in advanced stage (Child-Pugh B or C)
Active drug- or alcohol abuse
Not being able to tolerate a 28-day washout of one of the drugs interfering
with diuretic testing.
Women who are pregnant, breastfeeding, or considering pregnancy in the coming 7
weeks
Design
Recruitment
Medical products/devices used
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 | NL87576.078.24 |