Randomised controlled trials (RCTs) that compared combined therapy of an angiotensin-converting enzyme inhibitor plus an angiotensin receptor blocker versus monotherapy with either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker were eligible for inclusion in the review. Trials were excluded if data for levels of proteinuria were not available or if participants had kidney disease other than primary glomerulonephritis or end-stage renal disease.
The primary outcome was absolute change in urinary excretion. Secondary outcomes included office blood pressure, glomerular filtration rate, and serum potassium levels. Withdrawal rate and adverse side effects were also of interest.
In almost 40% of included trials, patients had been previously treated with an angiotensin-converting enzyme inhibitor. A number of trials recruited only patients with immunoglobulin A nephropathy. In four trials an angiotensin-converting enzyme inhibitor and angiotensin receptor blocker were co-administered at a dose that was half that used in monotherapy. In all trials, the primary end-point was decrease in proteinuria. Included trials reported the following exclusion criteria: treatment with steroid/immunosuppressive agent at enrolment or in the previous three months (ten trials), severe cardiovascular disease (seven trials), severe hepatic disease (five trials), cancer (four trials), secondary hypertension (three trials), hyperkalaemia (two trials), and hypertension (two trials). Concomitant drugs were reported in the review, but use of non-steroidal anti-inflammatory drugs and anti-aldosterone drugs were not reported in any of the trials. For included participants, mean age was 44 years (range 25 to 60 years, where reported), mean baseline proteinuria was protein of 3.0g/d (range 0.8 to 7.9g/d), mean glomerular filtration rate was 71mL/min/1.73m2 (range 73 to 11071mL/min/1.73m2), urinary sodium excretion ranged from 170mmol/d to 219mmol/d (where reported), and the mean length of intervention was four months (range 1.5 to 12 months).
Two reviewers independently selected trials for inclusion in the review.