At the time of the start of the REIN-2 Trial, it was known that ACE inhibitors were renoprotective in patients with non-diabetic proteinuria CKD, but the big question for the REIN-2 trial was if more aggressive blood pressure control would delay progression to end-stage kidney disease. Specifically, would BP reduction lower than those in the original REIN study (DBP <90mmHg) slow the progression to dialysis? The MDRD study suggested this, but had the limitation that 48% of those in the intensive BP therapy group were on an ACE inhibitor as compared to only 28% in the conventional BP therapy group. Additionally, the AASK Trial as a whole did not show a slowing CKD progression when the study population was viewed as a whole (as compared to a subgroup analysis of those with proteinuria >1g/day).
The REIN-2 Trial randomized 338 hypertensive patients with non-diabetic CKD and proteinuria to conventional or intensive BP control. Patients had to have been on an ACE for at least 6 weeks and were required to have at least 1g/day proteinuria. Patients were randomized to conventional BP control (DBP target <90mmHg) or intensive BP control (BP <130/80mmHg). The primary outcome was time to ESKD over 36 months. Patients assigned to intensive BP control had no improvement in GFR decline or progression to ESKD. Overall, this trial showed that in patients with non-diabetic proteinuria CKD on an ACE inhibitor, further reduction of BP to a target of <130/80mmHg with a dihydropyridine CCB did not slow progression of ESKD. One limitation of this trial was that the difference in SBP between conventional BP target and intensive was only 4.1mmHg. Diastolic BP was only 2.8mmHg different.
The REIN-2 Trial: Ruggenenti, P., Perna, A., Loriga, G., Ganeva, M., Ene-Iordache, B., Turturro, M., ... & Garini, G. (2005). Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial. The Lancet, 365(9463), 939-946.
The REIN-2 Trial PMID: 15766995
Useful Summaries: Culleton, B., Ruggenenti, P., Perna, A., & Loriga, G. (2005). Intensified blood pressure (BP) control was not better than conventional BP control in non-diabetic chronic renal disease Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease REIN-2: multicentre, randomised controlled trial. Evidence-based Medicine, 10(5).