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Angiotensin II receptor blockers (ARB) are known to preserve kidney function among patients with kidney diseases and reduced renal function, but not among haemodialysis patients.
Haemodialysis patients often lose residual renal function after initiating dialysis leading to worsened quality of life, increased morbidity and mortality.
In this study an ARB is investigated in a double blind, randomised, parallel group, placebo controlled manner to see, if this ARB can save residual renal function among haemodialysis patients. Potential cardiovascular benefits of the treatment are also addressed.
Haemodialysis patients often lose residual renal function rather quickly after initiation of dialysis - average loss is 30 % per year. Loss of residual kidney function leads to deteriorating quality of life, more morbidity and a higher mortality. Many causes to this has been identified, but no one has - to my knowledge - addressed saving of residual renal function among haemodialysis patients so far.
Hypothesis: Irbesartan can reduce loss of residual kidney function among haemodialysis patients and left ventricular hypertrophy and arterial stiffness is less pronounced after 1 year of treatment.
Methods: 80 patients are randomised to receive either irbesartan, an angiotensin II receptor blocker (ARB), or placebo for 1 year. Residual renal function will be estimated before and one-two weeks after initiating project medicine, in order to estimate the acute effect of ARB on residual renal function in this study population. Thereafter, glomerular filtration rate (GFR) and urine volume will be determined after 3, 6, 9 and 12 months giving a regression line for each patient. 8 dialysis units will be recruiting patients.
Investigations:
Perspectives: It is well-known that ceased urine production has a tremendous negative effect on the quality of life of haemodialysis patients. Lately it was shown that residual renal function has greater impact than dialysis dose on morbidity as well as mortality. Among peritoneal dialysis patients in Asia an angiotensin-converting enzyme inhibitors (ACEI) or an ARB saved residual renal function, but preservation of renal function has not been addressed in haemodialysis patients, and ACEI or ARB are only prescribed to roughly 15 % of these.
If this study confirms our hypothesis the growing population of haemodialysis patients should be offered irbesartan.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Irbesartan | Active Comparator |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Irbesartan | Drug | Tablets, 300 mg * 1 daily, 1 year |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Decrease in loss of residual kidney function. | 3, 6, 9 and 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Cardio-vascular outcome assessed by applanation tonometry, echocardiography, Transonic measurements of cardiac output and markers in blood. | 1 year | |
| Progression to anuria | 3, 6, 9 and 12 months | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bente Jespersen, MD, DrMedSc | Department of Nephrology, Aarhus University Hospital, Skejby, Denmark | Study Chair |
| Erik Sloth, MD, DrMedSc | Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Skejby, Denmark | Study Chair |
| Jens Kristian D Jensen, MD, PhD | Department of Nephrology, Aarhus University Hospital, Skejby, Denmark | Study Chair |
| Krista D Kjærgaard, MD, PhD | Department of Nephrology, Aarhus University Hospital, Skejby, Denmark | Study Director |
| Christian D Peters, MD | Department of Nephrology, Aarhus University Hospital, Skejby, Denmark | Study Chair |
| Charlotte Strandhave, MD | Department of Nephrology, Aalborg University Hospital, Denmark | Principal Investigator |
| Ida N Tietze, MD, PhD | Department of Internal Medicine, Region Hospital Viborg, Denmark | Principal Investigator |
| Marija K Novosel, MD | Department of Internal Medicine, Region Hospital Fredericia, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Nephrology, Aarhus University, Aalborg | Aalborg | 9000 | Denmark | |||
| Department of Nephrology, Aarhus University Hospital, Skejby |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33115436 | Derived | Peters CD, Kjaergaard KD, Christensen KL, Bibby BM, Jespersen B, Jensen JD. High-sensitivity Troponin T in hemodialysis patients: a randomized placebo-controlled sub-study investigating angiotensin-II-blockade, variation over time and associations with clinical outcome. BMC Nephrol. 2020 Oct 28;21(1):452. doi: 10.1186/s12882-020-02103-1. | |
| 26030651 |
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| ID | Term |
|---|---|
| D007676 | Kidney Failure, Chronic |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| D000077405 | Irbesartan |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Placebo matching irbesartan 150 mg | Drug | Tablets, 300 mg * 1 daily, 1 year |
|
| Quality of life assessed by a questionnaire: Kidney Disease Quality Of Life - Short Form (KDQOL-SF) |
| 1 year |
| Aarhus N |
| 8200 |
| Denmark |
| Department of Medicine, Fredericia Hospital | Fredericia | 7000 | Denmark |
| Haemodialysis unit, Horsens Hospital | Horsens | 8700 | Denmark |
| Hemodialysis Unit, Randers Hospital | Randers | 8600 | Denmark |
| Department of Medicine M, Viborg Hospital | Viborg | 8800 | Denmark |
| Peters CD, Kjaergaard KD, Jensen JD, Christensen KL, Strandhave C, Tietze IN, Novosel MK, Bibby BM, Jespersen B. Short and Long-Term Effects of the Angiotensin II Receptor Blocker Irbesartan on Intradialytic Central Hemodynamics: A Randomized Double-Blind Placebo-Controlled One-Year Intervention Trial (the SAFIR Study). PLoS One. 2015 Jun 1;10(6):e0126882. doi: 10.1371/journal.pone.0126882. eCollection 2015. |
| 23651713 | Derived | Peters CD, Kjaergaard KD, Jespersen B, Christensen KL, Jensen JD. Renal and cardiovascular effects of irbesartan in dialysis patients--a randomized controlled trial protocol (SAFIR study). Dan Med J. 2013 Apr;60(4):A4602. |
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D013141 | Spiro Compounds |
| D013777 | Tetrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |