To investigate how acute potassium administration affects potassium and sodium balance in healthy subjects as compared to patients at different CKD stages, i.e., normal kidney function and stage 3b/4 CKD.
ID
Source
Brief title
Condition
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Serum potassium (in mmol/L).
Secondary outcome
Red Blood Cell (RBC) potassium (in mmol/L), renal potassium excretion, serum
sodium, renal sodium excretion, total body water, and systolic blood pressure,
as well as changes in serum bicarbonate, insulin, and plasma aldosterone.
Background summary
Potassium is the most abundant cation in the intracellular fluid and its
gradient across the cell membrane is pivotal for normal cell function. Under
normal conditions, the kidney is primarily responsible for maintaining total
body K+ (TBK) by matching potassium intake with potassium excretion. Yet, in
kidney patients our understanding of potassium handling after a potassium load
is incomplete. It is known, that as kidney function declines, the risk of
hyperkalemia increases. At the same time, advanced chronic kidney disease (CKD)
is often characterized by depleted TBK. Changes of the internal potassium
balance might become the most important regulator of the serum potassium
concentration in progressive CKD, but data to support this are lacking. Also,
many kidney patients are treated with RAAS inhibitors, because of the
renoprotective effects. However, RAAS inhibitor treatment is also associated
with elevated risk of hyperkalemia and might affect the acute potassium
balance. Of further interest is that potassium and sodium balance are closely
related. Under normal conditions, potassium supplementation increases sodium
excretion, but it is unknown whether this potassium-induced natriuresis remains
intact in CKD. In summary, better understanding of potassium homeostasis in
response to potassium loading in CKD is highly relevant, specifically in the
context of exploring the potentially beneficial effects of potassium
supplementation in patients with CKD
Study objective
To investigate how acute potassium administration affects potassium and sodium
balance in healthy subjects as compared to patients at different CKD stages,
i.e., normal kidney function and stage 3b/4 CKD.
Study design
Double blind and placebo-controlled cross-over study.
Intervention
Patients and healthy subjects will be randomized to a 8-week period with RAAS
inhibitor treatment (Lisinopril 10 mg once daily) followed by a 8-week period
without RAAS inhibitor treatment (or vice versa). After 6, 7 and 8 weeks an
acute oral dose of potassium chloride (40 mmol), potassium citrate (40 mmol) or
matching placebo will be administered in random order.
Study burden and risks
Participating in this research project will not lead to personal benefit.
However, little to no burden is expected when participating in this study. The
subjects will be asked to visit our research department seven times which will
take approximately 29 hours in total. The study visits comprise venous blood
drawings, spot urine samples, collection of 24-hour urine, faeces sample,
measurements of volume status (using weight and bioimpedance measurements) and
central and peripheral hemodynamics (by using continuous finger arterial
pressure [FinAp] waveform registration, Nexfin®, Sphygmocor® and an automated
device for peripheral BP measurement (Omron®)). In addition, RAAS inhibition
may affect blood pressure and withdrawal of RAAS inhibition in patients might
result in hypertension. In healthy subjects RAAS inhibition might cause
hypotension. Therefore, blood pressure will be measured once in two weeks.
Meibergdreef 9
Amsterdam-Zuidoost 1105 AZ
NL
Meibergdreef 9
Amsterdam-Zuidoost 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Patients:
• Adult patients (>= 18 years) with CKD 3b or 4 (45 - 15 ml/min/1.73 m2).
• Hypertension (defined as office blood pressure > 140/90 mmHg and using single
RAAS inhibitor treatment)., Healthy subjects:
• Healthy adults (>= 18 years), as determined by a responsible and experienced
physician, based on a medical evaluation including medical history, physical
examination (PE) and laboratory tests carried out in the screening visit (V0).
• Using no medication (excluding contraceptives).
Exclusion criteria
Patients:
• Hyperkalemia (serum potassium > 5.5 mmol/l).
• Medical reasons to continue dual RAAS-blockade, mineralocorticoid receptor
blockers, potassium-sparing diuretics, or oral potassium binders.
• Patients with previous history of ventricular cardiac arrhythmia.
• Patients with diabetes mellitus.
• Patients with a life expectancy < 6 months.
• Expected initiation of renal replacement therapy < 6 months.
• Incapacitated subjects.
• Women who are pregnant, breastfeeding or consider pregnancy in the coming 6
months., Healthy subjects:
• Hyperkalemia (serum potassium > 5.5 mmol/l).
• Women who are pregnant, breastfeeding or consider pregnancy in the coming 6
months.
• An office blood pressure >= 140/90 mmHg.
• A body mass index >= 30 kg/m2.
• A major illness in the past 3 months or any significant chronic medical
illness that the investigator would deem unfavourable for enrolment, including
diabetes mellitus.
• A history of any type of malignancy within the past 5 years with the
exception of successfully treated basal cell carcinoma of the skin.
• A history of any renal disease.
• A history of any blood clotting disorders.
• A history of any auto-immune disease.
• A history of cardiovascular disease (in the past 6 months) defined as
documented coronary artery disease including myocardial infarction (MI),
(un-)stable angina pectoris or acute coronary syndrome (ACS), percutaneous
transluminal coronary angioplasty (PTCA), coronary artery bypass grafting
(CABG), cerebrovascular disease, including ischaemic and haemorrhagic stroke or
a subarachnoid bleeding (SAB), or peripheral artery disease, including aortic
aneurysmata (AA).
• A history of ventricular cardiac arrhythmia.
• Any significant sign or symptom of hypotension.
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 | NL65498.018.18 |