Angiotensin Converting Enzyme (ACE) inhibition for the preservation of renal function and patient survival in kidney transplantation

1. A composite measure incorporating the following clinically important endpoints:
1.1. Doubling of serum creatinine
1.2. End-stage renal disease or death
2. Time points of measurement:
2.1. Doubling of serum creatinine will be confirmed by two consecutive tests at least four weeks apart in a central laboratory. The base creatinine for the primary outcome will be the creatinine performed at the time of randomisation.
2.2. End-stage renal disease will be defined as the date the patient undergoes repeat kidney transplantation or starts dialysis
2.3. Death defined as the date the patient dies

1. Rate of decline in glomerular filtration rate (radioisotopic method), measured at baseline and then every six months thereafter
2. Urine protein excretion (24 hour urine), measured at baseline and then every six months thereafter
3. Systolic and diastolic blood pressure, measured at screening, baseline, one month, two months (only if BP is 130/80 mmHg at one month), six months and every six months thereafter. Amended as of 12/11/2009 to: Patients will return one month after the study visit to either their family physicians or transplant clinic for follow-up blood pressure monitoring each time their blood pressure is greater than 130/80 mmHg.
4. Incidence of adverse events: early rise in serum creatinine (greater than 30% increase from baseline), hyperkalemia (potassium = 5.5 mmol/l), and anemia (haemoglobin less than 110 g/l in women and less than 120 g/l in men), serum creatinine (Cr) and potassium will be measured at screening, baseline, two weeks, one month, six months, and every six months thereafter. At each visit, the serum Cr compared to the baseline sample taken at randomisation to determine if a doubling in Cr has occurred. Haemoglobin will be measured at baseline, two weeks, one month, six months, and every six months thereafter.
5. Incidence of cardiovascular events, documentation will be gathered for review by a blinded adjudication committee.
6. Total number of hospitalisations, will be measured at each follow-up visit (every six months) and well documented on case report forms
7. Health-related quality of life, generic (SF-36 v2 health survey) and utility measure (EuroQOL-5D). Quality of life questionnaires will be completed by patients at baseline, six months, 12 months and then annually.
8. Health care resource utilisation, will be measured at each visit - baseline and every six months thereafter

Added as of 16/07/2008:
9. Clinically meaningful diagnostic characteristics of serum Cystatin C and beta trace protein will be measured at each visit-baseline and every 6 months thereafter

Added as of 12/11/2009 (latest ethics amendment in October 2009):
10. Serum storage: each participant will be asked to allow any serum remaining after every 6-month testing, to be stored for up to 15 years for:
10.1. Possible recalculation of creatinine
10.2. Quality assurance (calibration of Cystatin C)
10.3. Potential future testing for novel markers of kidney disease
Serum samples will be stored at -80°C at the EORLA Research Lab (The Ottawa Hospital General Campus). Any future testing would be submitted to a REB for approval. Serum will eventually be destroyed using standard operating laboratory procedures at The Ottawa Hospital.