Disorder Related to Renal Transplantation
Conditions
Keywords
Fibrosis, calcineurin inhibitor, kidney transplant, chronic rejection
Brief summary
The purpose of this study is to assess whether the diuretic drug spironolactone can prevent chronic damage to transplanted kidneys caused by the medication that prevents rejection. Spironolactone prevents the effects of the hormone aldosterone. Aldosterone is suspected of being involved in the processes leading to chronic rejection of transplanted kidneys. Hence, by blocking the effects of aldosterone we hope to be able to prevent loss of kidney function in transplant patients.
Detailed description
AIM: The purpose of this study is to assess whether spironolactone can prevent the formation of fibrosis in transplanted kidneys. BACKGROUND: Calcineurin inhibitors (CNI) are one of the cornerstones of immunosuppressive therapy after kidney transplantation. The introduction of CNI has caused a significant decrease in acute rejections. However, CNI also have known side effects. These include the formation of tubulointerstitial fibrosis in the transplanted kidney, contributing over time to impaired kidney function and reduced graft survival. The mineralocorticoid aldosterone may be involved in the development of renal fibrosis. Recent observations suggest that aldosterone plays a central role in the pathogenesis of CNI nephrotoxicity and that the mineralocorticoid-receptor-blocker spironolactone could be a useful agent to prevent it. METHODS: This study is a randomized, placebo-controlled, double-blind study in which 170 renal transplant patients will be recruited from two nephrological departments in Southern Denmark. Patients will be randomized to three years of treatment with either spironolactone or placebo added to the standard immunosuppressive treatment. Renal graft biopsies, various molecular tests of tissue, blood and urine, chrome-EDTA clearance, 24-hour bloodpressure measurement and blood samples will be performed at inclusion, after 1 year, 2 years and upon completion.
Interventions
DRUGSpironolactone
One tablet per day (25 mg Spironolactone/placebo) for the first three months. Subsequently dosage is increased to two tablets per day (50 mg Spironolactone/placebo) for the rest of the study. In case of hyperkaliemia (\>5,5 mmol/L) or intolerable side effects dosage will be reduced to one tablet per day (25 mg Spironolactone/placebo).
DRUGplacebo
Sponsors
Fredericia Hosptial
Odense University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \> 18 years 2. Proteinuria \< 3 g/24 hours 3. Creatinine clearance ≥ 30 mL/min 4. S-Potassium \< 5,5 mmol/L 5. Negative pregnancy test at the inclusion and anticonception
Exclusion criteria
1. Intolerance to spironolactone 2. Creatinine clearance \< 30 ml/min 3. S-Potassium ≥ 5,5 mmol/L 4. Resin or digoxine treatment 5. Pregnancy or planned pregnancy 6. Relevant organic, systemic or mental illness 7. Anticipation of lack of compliance or understanding the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Cr EDTA clearance | 0, 1 year, 2 years, 3 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduced urine protein levels (change from baseline) | 0, 1 year, 2 years, 3 years | — |
| Reduced fibrosis (change from baseline) | 0, 2 years | Verified by graft biopsies and immuno histochemistry. Newly transplanted patients will be subjected to additional biopsies 3 months and 1 year after inclusion. |
| Reduced blood pressure (change from baseline) | 0, 1 year, 2 years, 3 years | — |
| Cardiovascular events | 3 years | — |
Countries
Denmark
Outcome results
None listed