The VA NEPHRON-D study looked at combination therapy of ACE Inhibitors and ARBs (angiotensin receptor blockers) in in those with diabetic nephropathy. The two drugs used in the trial were losartan and lisinopril and follow-up was 2.2 years. Primary end-points were first change in GFR, end-stage renal disease or death. Safety outcomes included all-cause mortality, hyperkalemia and acute kidney injury. Combination therapy increased risk for hyperkalemia at 6.3 events per 100 person-years versus 2.6 with monotherapy. Acute kidney injury occurred at a rate of 12.2 events per 100 person years versus 6.7 events (p<0.001). The trial was stopped early due to these profound adverse results.
The conclusion is that combination therapy in those with diabetic nephropathy is not warranted due to the significant increase in risk for adverse events.