chronic kidney disease reduced kidney function gradual loss of kidney function
Conditions
Interventions
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, 11 healthy controls will 
undergo the test to compare the diuretic response in patients with CKD to 
healthy participants (age and sex matched).
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Adult (>= 18 years) CKD stage G3 (creatinine-based eGFR 30-59 mL/min/1.73m2) during the last outpatient visit
Exclusion criteria
Exclusion criteria: Known intolerance or allergy to the diuretics Current systemic chemotherapy for malignancy Kidney transplant recipient Use of calcineurin-inhibitors Life expectancy 5.5 mmol/L) at inclusion visit Hypo- or hypernatremia (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 outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Netherlands
Contacts
Public ContactSB Beckmann
Erasmus MC, Universitair Medisch Centrum Rotterdam
Outcome results
None listed