Renal Transplant Donor of Left Kidney, Renal Transplant Donor of Right Kidney
Conditions
Keywords
Uric acid, Left ventricular mass, Nephrectomy, Allopurinol, Magnetic resonance imaging
Brief summary
Recently there was described an increase in left ventricular mass after kidney donation. It is uncertain whether this is reversible or not. Allopurinol lowers uric acid in the blood and is normally indicated for gout, but studies have showed that it also can reduce the thickness of the left ventricle of the heart in people with heart- and kidney disease. The investigators wish to give allopurinol or placebo to kidney donors based on randomization and investigate if this has the same effect on kidney donors. The investigators are assessing this by performing a cardiac MRI at baseline and after 9 months of treatment. In addition the investigators wish to see if allopurinol can have beneficial effects on blood pressure and insulin sensitivity as well.
Interventions
DRUGPlacebo Oral Tablet
placebo oral tablets given to participants once daily for 9 months
Allopurinol oral tablets 300 mg given to participants once daily for 9 months
Sponsors
South-Eastern Norway Regional Health Authority
University of Oslo
Oslo 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. Kidney donor ≥ 6 months after donor nephrectomy 2. Donor nephrectomy undertaken in Norway 3. Male or female subject ≥ 18 years old 4. eGFR \>30 ml/min/1.73 m2 5. Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.
Exclusion criteria
1. Adverse reactions to allopurinol or other xanthine oxidase inhibitors 2. Use of uric acid lowering therapy within 3 months 3. History of gout, xanthinuria or other indications for uric acid lowering therapy such as cancer chemotherapy 4. History of renal calculi 5. History of coronary heart disease 6. Heart failure with left ventricular ejection fraction \<45% 7. History of significant (i.e. non-physiological) cardiac valvular stenosis or insufficiency 8. History of clinically significant hepatic disease including hepatitis B or C and/or ALAT (SGPT) above the upper reference limit at screening. 9. History of HIV or AIDS 10. Severe systemic infections, current or within the last 6 months 11. History of malignancy other than localized basal cell carcinoma of the skin, treated or untreated, within the past 5 years. 12. Other life-threatening diseases 13. Haemoglobin concentration \< 11 g/dL(males), \<10 g/dL (females); white blood cell (WBC) count \< 3.5 \* 10\^9/L; platelet count \<50 \*10\^9/L at screening 14. Use of the following medications at or within 14 days before the screening visit: azathioprine, mercaptopurine, vidarabin, chlorpropamide, warfarin, tamoxifen, theophylline, amoxicillin/ampicillin, cyclophosphamide, doksorubicin, bleomycin, prokarbazin, cyclosporine, didanosine. 15. Contraindications to MRI, including: Magnetic intracranial clips. Metal fragments in orbita. Cochlea (ear) implant. Neurostimulator. Pacemaker/ICD or remaining pacemaker electrodes. Harrington rods in thorax. Claustrophobia. Unable to lie supine. 16. Pregnant or nursing (lactating) women 17. Fertile women, unless they are using effective contraception during dosing of study treatment 18. Any reason why, in the opinion of the investigator, the patient should not participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in left ventricular mass | Nine months | Measured change in left ventricular mass using Cardiac MRI, comparing from baseline to 9 months of treatment With allopurinol compared to placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in blood pressure | Nine months | Change from baseline to 9 months in the allopurinol group compared to placebo in systolic and diastolic ambulatory blood pressure, systolic and diastolic Office blood pressure. |
| Estimated insulin sensitivity, metabolic clearance rate of glucose | Nine months | Change from baseline to 9 months in the allopurinol group compared to placebo in insulin sensitivity using an orgal glucose tolerance test to measure estimated metabolic clearance rate of glucose, insulin sensitivity, firth-phase insulin release and second-phase insulin release. |
| Number of antihypertensive medications | Nine months | Change from baseline to 9 months in the allopurinol group compared to placebo in number of antihypertensive medications |
| Change in urinary albumin excretion | Nine months | Change from baseline to 9 months in the allopurinol group compared to placebo in urinary albumin excretion by measuring urinary albumin/creatinine ratio. |
| Change in estimated GFR | Nine months | Change from baseline to 9 months in the allopurinol group compared to placebo in estimated GFR |
| Doses of antihypertensive medications | Nine months | Change from baseline to 9 months in the allopurinol group compared to placebo in doses of antihypertensive medications |
Countries
Norway
Outcome results
None listed