To measure changes in urinary RAS components during an acid-loading test in patients with CKD and healthy controls.
ID
Source
Brief title
Condition
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study parameter is the change in urinary renin values (an accepted
measure of intrarenal RAS activity).
Secondary outcome
Not applicable
Background summary
Metabolic acidosis is one of the metabolic complications of chronic kidney
disease (CKD). Correction of metabolic acidosis in CKD has been shown to
prevent further loss of kidney function over time. Currently, we are conducting
a clinical trial (the BIC-study, MEC-2013-332) in which patients with CKD and
metabolic acidosis receive sodium bicarbonate, sodium chloride, or no treatment
(time control) to address the hypothesis that the beneficial effects of
acidosis correction are mediated through inhibition of the intrarenal
renin-angiotensin system (RAS). It is unknown, however, if and how acute
changes in acid-base status affect the intrarenal RAS during CKD. In the
present study we hypothesize that an acute acid load increases the activity of
the intrarenal RAS, and that this response is exaggerated in patients with CKD
compared with healthy controls.
Study objective
To measure changes in urinary RAS components during an acid-loading test in
patients with CKD and healthy controls.
Study design
Diagnostic test
Intervention
All participants will undergo a urinary acidification test with ammonium
chloride.
Study burden and risks
All subjects will receive ammonium chloride (100 mg/kg body weight, given
orally) during a single-day hospital admission. For blood drawing a catheter
will be inserted in a forearm vein. The test requires 3 venous blood
collections and collection of all urine produced over the course of 8.5 hours.
Oral ammonium chloride can cause abdominal discomfort and nausea (0-10%), and
in some cases vomiting (0-6%). Venous catheter placement might cause physical
discomfort. There is a very small risk of infection (thrombophlebitis) or
hematoma at the puncture place.
Dr. Molenwaterplein 50
Rotterdam 3015GE
NL
Dr. Molenwaterplein 50
Rotterdam 3015GE
NL
Listed location countries
Age
Inclusion criteria
Patients with CKD:
- Male or female adults (*18 years)
- Chronic kidney disease stage 4 (eGFR: 15-30 ml/min/1.73 m2)
Healthy subjects:
- Healthy male or female adults (* 18 years)
- Normal kidney function (eGFR > 90 ml/min/1.73 m2)
Exclusion criteria
Patients with CKD:
- Plasma bicarbonate level < 20.0 mmol/l
- Serum potassium >5.5 mmol/l
- Sodium bicarbonate use in the month preceding the study
- Heart failure (NYHA III or IV)
- Liver cirrhosis (Child Pugh B or C)
- Blood pressure >140/90 mmHg despite the use of 3 different anti-hypertensives
- Kidney transplantation
- Use of calcineurin inhibitors
- Known urea cycle disorder
- Alcoholism or drug use
- Pregnancy
- Current use of antibiotics, NSAIDS or alkalizing drugs (sodium-bicarbonate, citric acid, potassium citrate, acetazolamide)
- Inability to adhere to the study protocol (due to language barrier or intellectual disability);Healthy subjects:
- eGFR < 90 ml/min/1.73 m2
- plasma bicarbonate < 20 mmol/l.
- History of, or drugs for, diabetes mellitus
- History of chronic diarrheal disease
- Ileostomy/colostomy
- Known urea cycle disorder
- Alcoholism or drug use
- Pregnancy
- Current use of antibiotics, antihypertensive drugs, NSAIDS or alkalizing drugs
- Inability to adhere to the study protocol (due to language barrier or intellectual disability)
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 | NL57148.078.16 |