Eligible for inclusion were randomised controlled trials that evaluated folic acid based homocysteine lowering therapy compared with different doses, placebo or usual care in people with kidney disease. Trials had to have a minimum of 100 patient years of follow-up. Sequential or crossover trial designs were excluded. Participants could be in receipt of maintenance dialysis or a functioning kidney transplant. The primary outcome of interest was cardiovascular events (myocardial infarction, stroke and cardiovascular death). Secondary outcomes of interest were all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, leg amputation, dialysis access thrombosis and the start of renal replacement therapy in people not requiring dialysis. Adverse events were also analysed.
Included participants had chronic and/or end-stage kidney disease or a functioning kidney transplant. Sixty-four percent (median) were men (range 50 to 98%). The mean age of participants ranged from 48.5 to 72.2 years; average (median) proportion with a diagnosis of diabetes was 40% (range 11 to 100%); average (median) proportion with a history of cardiac disease was 34% (range 11 to 100%). Daily oral folic acid supplementation ranged from 2.5mg to 40mg; some trials included additional supplementation with Vitamin B.
Two reviewers independently selected the trials for inclusion.